CAZypedia - User contributions [en-ca]

Syn/anti lateral protonation

2026-04-16T14:46:50Z

Wim Nerinckx:

{{CuratorApproved}}
* [[Author]]: [[User:Wim Nerinckx|Wim Nerinckx]]
* [[Responsible Curator]]: [[User:Spencer Williams|Spencer Williams]]

----

== Overview ==

This page provides a table that summarizes the spatial positioning of the catalytic [[general acid]] residue in the active sites of [[glycoside hydrolase]]s, relative to the substrate. The table below updates those found in the seminal paper on this concept by Heightman and Vasella <cite>HeightmanVasella1999</cite>, and a following paper by Nerinckx ''et al.'' <cite>Nerinckx2005</cite>.

== Background ==

The ''"not from above, but from the side"'' concept of semi-lateral glycosidic oxygen [[General_acid/base|protonation]] by [[glycoside hydrolase]]s was introduced by Heightman and Vasella <cite>HeightmanVasella1999</cite>. It was originally only described for [[Anomeric centre (alpha and beta)|beta]]-equatorial [[glycoside hydrolase]]s, but appears to be equally applicable to enzymes acting on an [[Anomeric centre (alpha and beta)|alpha]]-axial glycosidic bond <cite>Nerinckx2005</cite>. When dividing [[Sub-site nomenclature|subsite -1]] into half-spaces by a plane defined by the glycosidic oxygen and C1' and H1' of the –1 glycoside, many ligand-complexed structures reveal that the [[General_acid/base|proton donor]] is positioned either in the ''syn'' half-space (near the ring-oxygen of the –1 glycoside), or in the ''anti'' half-space (on the opposite side of the ring-oxygen). Members of the same GH [[Families|family]] appear to share a common ''syn'' or ''anti'' [[General_acid/base|protonator]] arrangement and further, this specificity appears to be preserved within [[Clans|Clans]] of [[Families|families]]. This page's compilation of [[Sub-site nomenclature|subsite -1]] occupied complexes shows that about 70% of all GH [[Families|families]] are ''anti'' [[General_acid/base|protonators]].

Closer inspection of crystal structures of [[Sub-site nomenclature|–1/+1 subsite]]-spanning substrates, or substrate-analogue ligands, in complex with enzymes reveals a further intriguing corollary <cite>Nerinckx2005 Wu2012</cite>. In substrate-bound complexes with ''anti'' [[General_acid/base|protonating]] GH enzymes, the scissile [[Anomeric centre (alpha and beta)|anomeric bond]] (often studied using the thio-analogue) shows a dihedral angle φ (O5'-C1'-[O,S]x-Cx) that is in the lowest-energy synclinal (gauche) conformation. The rationale for this is that a minus synclinal dihedral angle φ for an equatorial glycosidic bond, or plus synclinal for an axial glycosidic bond <cite>Perez1978</cite>, allows for hyperconjugative overlap of the C1'-O5' antibonding orbital with an antiperiplanar-oriented lone pair orbital lobe of the glycosidic oxygen, thereby creating partial double bond character and stabilization of the glycosidic bond by 4–5 kcal/mol; this ground-state stabilizing phenomenon is known as the ‘exo-anomeric effect’ <cite>Cramer1997 Johnson2009 Alonso2016</cite>. ''Anti'' [[General_acid/base|protonation]] occurs on the glycosidic oxygen’s antiperiplanar lone pair, thereby removing the stabilizing exo-anomeric effect. This suggests that ''anti'' [[General_acid/base|protonation]] is an enzymic approach for lowering the activation barrier leading to the [[Transition state|transition state]] (Figure 1 centre).

''Syn'' [[General_acid/base|protonating]] [[glycoside hydrolase]]s apparently make use of a different approach <cite>Nerinckx2005 Wu2012</cite>. In many [[Sub-site nomenclature|–1/+1 subsite]]-spanning ligand complexes, the dihedral angle φ of the scissile anomeric bond has been rotated away from its lowest-energy synclinal position: clockwise to minus-anticlinal or antiperiplanar for beta-equatorial; counterclockwise to plus-anticlinal or antiperiplanar for alpha-axial [[Anomeric centre (alpha and beta)|anomeric bonds]]. This removes the hyperconjugative overlap and thus also the stabilizing exo-anomeric effect. And because of this rotation, a lone pair of the glycosidic oxygen is directed into the ''syn'' half-space, allowing it to be protonated by the ''syn''-positioned [[General_acid/base|proton donor]] (Figure 1 right).

[[File:Syn_anti.jpg|800px|thumb|center|Figure 1. Newman projections, with the glycosidic oxygen as proximal atom and the anomeric carbon as distal atom, showing ''anti'' (centre) versus ''syn'' (right) semi-lateral [[General_acid/base|protonation]] in beta-equatorial (top) and alpha-axial (bottom) [[glycoside hydrolase]]s. The indicated φ is the dihedral angle for O5'-C1'-O4-C4.]]

== Table of ''syn/anti'' protonation examples ==

This table contains only one example per GH [[Families|family]] of a ligand-complexed protein structure where the ''syn'' or ''anti'' positioning of the [[General_acid/base|proton donor]] can be clearly observed; other examples may be available on a [[Families|family-by-family]] basis. The reader is thus advised to consult the [http://www.cazy.org/fam/acc_GH.html#table CAZy database] for a current, comprehensive list of CAZyme structures. Where available, the selected examples are Michaelis-type complexes with the ligand spanning the [[Sub-site nomenclature|-1/+1 subsites]], since these have an intact glycosidic or thioglycosidic bond, or are ''N''-analogs of the substrate (''e.g.'' acarbose). In some examples, the [[General_acid/base|proton donor]] has been mutated (''e.g.'', to the corresponding amide or to an alanine), and in those cases one may wish to look at a superposition of the given PDB example with the structure of the native enzyme. If a Michaelis-type complex is not yet available, the second and third example choices, respectively, are trapped glycosyl-enzyme [[intermediate]]s and product complexes where [[Sub-site nomenclature|subsite -1]] is occupied.

''Please also be aware that this is a large table with many data. Please contact the page Author or Responsible Curator with corrections.''

=== Table ===
This table can be re-sorted by clicking on the icons in the header (''javascript must be turned on in your browser''). To reset the page to be sorted by GH family, click the ''View'' tab at the very top of the page.

{| {{Prettytable}} class="sortable"
|- valign="top"
! '''Family'''
! '''Clan'''
! '''Structure fold '''
! '''Anomeric specificity'''
! '''Mechanism'''
! '''''Syn/anti'' protonator'''
! '''Example PDB ID'''
! '''Enzyme'''
! '''Organism'''
! '''Ligand'''
! '''General acid'''
! '''Nucleophile or General base'''
! '''Reference'''
|-
| [[GH1]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002cer pdb_00002cer]
| β-glycosidase S
| ''Sulfolobus solfataricus'' P2
| phenethyl glucoimidazole
| '''Glu206'''
| Glu387
| <cite>Gloster2006</cite>
|-
| [[GH2]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002vzu pdb_00002vzu]
| exo-β-glucosaminidase
| ''Amicolatopsis orientalis''
| PNP-β-{{Smallcaps|d}}-glucosamine
| '''Glu469'''
| Glu541
| <cite>van_Bueren2009</cite>
|-
| [[GH3]]
| none
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001iex pdb_00001iex]
| exo-1,3-1,4-glucanase
| ''Hordeum vulgare''
| thiocellobiose
| '''Glu491'''
| Asp285
| <cite>Hrmova2001</cite>
|-
| [[GH4]]
| none
| Rossmann + α6/β3 + β3/α4
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001u8x pdb_00001u8x]
| 6-P-α-glucosidase
| ''Bacillus subtilis''
| alpha-{{Smallcaps|d}}-glucose-6-phosphate
| '''Asp172'''
| not applicable
| <cite>Rajan2004</cite>
|-
| [[GH5]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001h2j pdb_00001h2j]
| endo-β-1,4-glucanase
| ''Bacillus agaradhaerens''
| 2',4'-DNP-2-F-cellobioside
| '''Glu129'''
| Glu228
| <cite>Varrot2003</cite>
|-
| [[GH6]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00001qjw pdb_00001qjw]
| cellobiohydrolase 2
| ''Hypocrea jecorina''
| (Glc)2-S-(Glc)2
| '''Asp221'''
| debated
| <cite>Zhou1999</cite>
|-
| [[GH7]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00001ovw pdb_00001ovw]
| endo-1,4-glucanase
| ''Fusarium oxysporum''
| thio-(Glc)5
| '''Glu202'''
| Glu197
| <cite>Sulzenbacher1999</cite>
|-
| [[GH8]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00001kwf pdb_00001kwf]
| endo-1,4-glucanase
| ''Clostridium thermocellum''
| cellopentaose
| '''Glu95'''
| Asp278
| <cite>Guerin2002</cite>
|-
| [[GH9]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00001rq5 pdb_00001rq5]
| cellobiohydrolase
| ''Clostridium thermocellum''
| cellotetraose
| '''Glu795'''
| Asp383
| <cite>Schubot2004</cite>
|-
| [[GH10]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002d24 pdb_00002d24]
| β-1,4-xylanase
| ''Streptomyces olivaceoviridis'' E-86
| xylopentaose
| '''Glu128'''
| Glu236
| <cite>Suzuki2009</cite>
|-
| [[GH11]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00004hk8 pdb_00004hk8]
| endo-β-1,4-xylanase
| ''Hypocrea jecorina''
| xylohexaose
| '''Glu177'''
| Glu86
| <cite>Wan2014</cite>
|-
| [[GH12]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00001w2u pdb_00001w2u]
| endoglucanase
| ''Humicola grisea''
| thiocellotetraose
| '''Glu205'''
| Glu120
| <cite>Sandgren2004</cite>
|-
| [[GH13]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001cxk pdb_00001cxk]
| β-cyclodextrin glucanotransferase
| ''Bacillus circulans''
| maltononaose
| '''Glu257'''
| Asp229
| <cite>Uitdehaag1999</cite>
|-
| [[GH14]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00001itc pdb_00001itc]
| β-amylase
| ''Bacillus cereus''
| maltopentaose
| '''Glu172'''
| Glu367
| <cite>Miyake2003</cite>
|-
| [[GH15]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00001dog pdb_00001dog]
| glucoamylase
| ''Aspergillus awamori''
| 1-deoxynojirimycin
| '''Glu179'''
| Glu400
| <cite>Harris1993</cite>
|-
| [[GH16]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00001urx pdb_00001urx]
| β-agarase A
| ''Zobellia galactanivorans''
| oligoagarose
| '''Glu152'''
| Glu147
| <cite>Allouch2004</cite>
|-
| [[GH17]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00004gzj pdb_00004gzj]
| endo-β-1,3-glucanase
| ''Solanum tuberosum''
| laminaratriose + laminarabiose
| '''Glu118'''
| Glu259
| <cite>Wojtkowiak2013</cite>
|-
| [[GH18]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001ffr pdb_00001ffr]
| chitinase A
| ''Serratia marcescens''
| (NAG)6
| '''Glu315'''
| internal
| <cite>Papanikolau2001</cite>
|-
| [[GH19]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00003wh1 pdb_00003wh1]
| chitinase
| ''Bryum coronatum''
| (GlcNAc)4
| '''Glu61'''
| Glu70
| <cite>Ohnuma2014</cite>
|-
| [[GH20]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001c7s pdb_00001c7s]
| chitobiase
| ''Serratia marcescens''
| chitobiose
| '''Glu540'''
| internal
| <cite>Prag2000</cite>
|-
| [[GH22]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00001h6m pdb_00001h6m]
| lysozyme C
| ''Gallus gallus''
| Chit-2-F-chitosyl
| '''Glu35'''
| Asp52
| <cite>Vocadlo2001</cite>
|-
| [[GH23]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00001lsp pdb_00001lsp]
| lysozyme G
| ''Cygnus atratus''
| Bulgecin A
| '''Glu73'''
| internal
| <cite>Karlsen1996</cite>
|-
| [[GH24]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_0000148l pdb_0000148l]
| lysozyme E
| Bacteriophage T4
| chitobiosyl
| '''Glu11'''
| Glu26
| <cite>Baldwin1993</cite>
|-
| [[GH26]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002vx6 pdb_00002vx6]
| exo-β-mannanase
| ''Cellvibrio japonicus'' Ueda107
| Gal1Man4
| '''Glu221'''
| Glu338
| <cite>Cartmell2008</cite>
|-
| [[GH27]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}} / beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00003lrm pdb_00003lrm]
| α-galactosidase
| ''Saccharomyces cerevisiae''
| raffinose
| '''Asp209'''
| Asp141
| <cite>Fernandez-Leiro2010</cite>
|-
| [[GH28]]
| N
| β-helix
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00002uvf pdb_00002uvf]
| exo-polygalacturonosidase
| ''Yersinia enterocolitica'' ATCC9610D
| digalacturonic acid
| '''Asp402'''
| Asp381 Asp403
| <cite>Abbott2007</cite>
|-
| [[GH29]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00003uet pdb_00003uet]
| α-1,3/4-fucosidase
| ''Bifidobacterium longum'' subsp. infantis
| lacto-''N''-fucopentaose II
| '''Glu217'''
| Asp172
| <cite>Sakurama2012</cite>
|-
| [[GH30]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002y24 pdb_00002y24]
| glucurono-xylanase
| ''Dickea chrysanthemi'' D1
| glucuronoxylan tetrasaccharide
| '''Glu165'''
| Glu253
| <cite>Urbanikova2011</cite>
|-
| [[GH31]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002qmj pdb_00002qmj]
| maltase-glucoamylase
| ''Homo sapiens''
| acarbose
| '''Asp542'''
| Asp443
| <cite>Sim2008</cite>
|-
| [[GH32]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002add pdb_00002add]
| fructan β-(2,1)-fructosidase
| ''Cichorium intybus''
| sucrose
| '''Glu201'''
| Asp22
| <cite>Verhaest2007</cite>
|-
| [[GH33]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001s0i pdb_00001s0i]
| transsialidase
| ''Trypanosoma cruzi''
| sialyllactose
| '''Asp59'''
| Tyr342 (with Glu230)
| <cite>Amaya2004</cite>
|-
| [[GH34]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00004gzw pdb_00004gzw]
| N2 neuraminidase
| ''Influenza'' A Tanzania/205/2010 H3N2
| α-{{Smallcaps|d}}-Neup5Ac-(2,3)-β-{{Smallcaps|d}}-Galp-(1,4)-β-{{Smallcaps|d}}-GlcpNAc
| '''Asp151'''
| Tyr406 (with Glu277)
| <cite>Zhu2012</cite>
|-
| [[GH35]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00003ogv pdb_00003ogv]
| β-galactosidase
| ''Hypocrea jecorina''
| 2-phenylethyl 1-thio-β-{{Smallcaps|d}}-galactopyranoside
| '''Glu200'''
| Glu298
| <cite>Maksimainen2011</cite>
|-
| [[GH36]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00004fnu pdb_00004fnu]
| β-galactosidase
| ''Geobacillus stearothermophilus''
| stachyose
| '''Asp584'''
| Asp478
| <cite>Merceron2012</cite>
|-
| [[GH37]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00002jf4 pdb_00002jf4]
| trehalase
| ''Escherichia coli''
| validoxylamine
| '''Asp312'''
| Glu496
| <cite>Gibson2007</cite>
|-
| [[GH38]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00003czn pdb_00003czn]
| Golgi α-mannosidase II
| ''Drosophila melanogaster''
| GlcNAcMan(5)GlcNAc(2)
| '''Asp341'''
| Asp204
| <cite>Shah2008</cite>
|-
| [[GH39]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002bfg pdb_00002bfg]
| β-xylosidase
| ''Geobacillus stearothermophilus''
| 2,5-dinitrophenyl-β-{{Smallcaps|d}}-xyloside
| '''Glu160'''
| Glu278
| <cite>Czjzek2005</cite>
|-
| [[GH42]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00004ucf pdb_00004ucf]
| β-galactosidase
| ''Bifidobacterium bifidum''
| {{Smallcaps|d}}-galactose
| '''Glu161'''
| Glu320
| <cite>Godoy2016</cite>
|-
| [[GH43]]
| F
| 5-fold β-propeller
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00003akh pdb_00003akh]
| exo-1,5-α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces avermitilis''
| α-1,5-arabinofuranotriose
| '''Glu196'''
| Asp220
| <cite>Fujimoto2010</cite>
|-
| [[GH44]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002eqd pdb_00002eqd]
| endoglucanase
| ''Clostridium thermocellum''
| cellooctaose
| '''Glu186'''
| Glu359
| <cite>Kitago2007</cite>
|-
| [[GH45]]
| none
| 6-stranded β-barrel
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00004eng pdb_00004eng]
| endo-1,4-glucanase
| ''Humicola insolens''
| cellohexaose
| '''Asp121'''
| Asp10
| <cite>Davies1996</cite>
|-
| [[GH46]]
| I
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00004olt pdb_00004olt]
| chitosanase
| ''Microbacterium sp.'' OU01
| hexa-glucosamine
| '''Glu25'''
| Asp43
| <cite>Lyu2014</cite>
|-
| [[GH47]]
| none
| (α/α)7
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00001x9d pdb_00001x9d]
| α-mannosidase I
| ''Homo sapiens''
| Me-2-S-(α-Man)-2-thio-α-Man
| '''Asp463'''
| Glu599
| <cite>Karaveg2005</cite>, <cite>Nerinckx2008</cite>
|-
| [[GH48]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH8''
|
|
|
|
|
|
|-
| [[GH49]]
| N
| β-helix
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH28''
|
|
|
|
|
|
|-
| [[GH50]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00004bq5 pdb_00004bq5]
| exo-β-agarase
| ''Saccharophagus degradans''
| neoagarotetraose
| '''Glu535'''
| Glu695
| <cite>Pluvinage2013</cite>
|-
| [[GH51]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001qw9 pdb_00001qw9]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Geobacillus stearothermophilus''
| PNP-{{Smallcaps|l}}-arabinofuranoside
| '''Glu175'''
| Glu294
| <cite>Hoevel2003</cite>
|-
| [[GH52]]
| O
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| '' predicted perpendicular by clan, see at GH116''
| [{{PDBlink}}pdb_00004c1p pdb_00004c1p]
| β-xylosidase
| ''Geobacillus thermoglucosidasius''
| xylobiose
| '''Asp517'''
| Glu537
| <cite>Espina2014</cite>
|-
| [[GH53]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002ccr pdb_00002ccr]
| β-1,4-galactanase
| ''Bacillus licheniformis''
| galactotriose
| '''Glu165'''
| Glu263
| <cite>Le_Nours2009</cite>
|-
| [[GH54]]
| none
| β-sandwich
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001wd4 pdb_00001wd4]
| α-{{Smallcaps|l}}-arabinofuranosidase B
| ''Aspergillus kawachii''
| {{Smallcaps|l}}-arabinofuranose
| '''Asp297'''
| Glu221
| <cite>Miyanaga2004</cite>
|-
| [[GH55]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00004tz5 pdb_00004tz5]
| exo-β-1,3-glucanase
| ''Streptomyces sp.'' SirexAA-E
| laminarihexaose
| '''Glu502'''
| unknown
| <cite>Bianchetti2015</cite>
|-
| [[GH56]]
| none
| (β/α)7
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001fcv pdb_00001fcv]
| hyaluronidase
| ''Apis mellifera''
| (hyaluron.)4
| '''Glu113'''
| internal
| <cite>Markovic-Housley2000</cite>
|-
| [[GH57]]
| T
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001k1y pdb_00001k1y]
| glucanotransferase
| ''Thermococcus litoralis''
| acarbose
| '''Asp214'''
| Glu123
| <cite>Imamura2003</cite>
|-
| [[GH59]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00004ccc pdb_00004ccc]
| β-galactocerebrosidase
| ''Mus musculus''
| PNP-β-{{Smallcaps|d}}-galactoside
| '''Glu182'''
| Glu258
| <cite>Hill2013</cite>
|-
| [[GH62]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00003wn0 pdb_00003wn0]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces coelicolor''
| β-{{Smallcaps|l}}-Arabinofuranose
| '''Glu361'''
| Asp202
| <cite>Maehara2014</cite>
|-
| [[GH63]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00005ca3 pdb_00005ca3]
| α-glucosidase
| ''Escherichia coli''
| glucose and lactose
| '''Asp501'''
| Glu727
| <cite>Miyazaki2016</cite>
|-
| [[GH65]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00004ktr pdb_00004ktr]
| 2-O-α-glucosylglycerol phosphorylase
| ''Bacillus selenitireducens''
| isofagomine
| '''Glu475'''
| phosphate
| <cite>Touhara2014</cite>
|-
| [[GH66]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00005axh pdb_00005axh]
| dextranase
| ''Thermoanaerobacter pseudethanolicus''
| isomaltohexaose
| '''Glu374'''
| Asp312
| <cite>Suzuki2016</cite>
|-
| [[GH67]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00001l8n pdb_00001l8n]
| α-glucuronidase
| ''Geobacillus stearothermophilus''
| 4-O-methyl-{{Smallcaps|d}}-glucuronic acid and xylotriose
| '''Glu286'''
| Asp364 Glu392
| <cite>Golan2004</cite>
|-
| [[GH68]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001pt2 pdb_00001pt2]
| levansucrase
| ''Bacillus subtilis''
| sucrose
| '''Glu342'''
| Asp86
| <cite>Meng2003</cite>
|-
| [[GH70]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00003aic pdb_00003aic]
| glucansucrase
| ''Streptococcus mutans''
| α-acarbose
| '''Glu515'''
| Asp477
| <cite>Ito2011</cite>
|-
| [[GH71]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00009fnh pdb_00009fnh]
| endo-α-1,3-glucanase
| ''Aspergillus nidulans'' FGSC A4
| nigerotetraose
| '''Glu268'''
| Asp265
| <cite>Mazurkewich2025</cite>
|-
| [[GH72]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002w62 pdb_00002w62]
| β-1,3-glucanotransferase
| ''Saccharomyces cerevisiae'' S288C
| laminaripentaose
| '''Glu176'''
| Glu275
| <cite>Hurtado-Gerrero2009</cite>
|-
| [[GH73]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| unknown
| '''''syn'''''
| [{{PDBlink}}pdb_00007pod pdb_00007pod]
| peptidoglycan endo-β-1,4-''N''-acetylglucosaminidase
| ''Streptococcus pneumoniae'' R6
| NAG-NAM-NAG-NAM tetrasaccharide
| '''Glu585'''
| unknown
| <cite>Martinez-Caballero2023</cite>
|-
| [[GH74]]
| none
| 7-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00002ebs pdb_00002ebs]
| cellobiohydrolase (OXG-RCBH)
| ''Geotrichum sp.'' m128
| xyloglucan heptasaccharide
| '''Asp465'''
| Asp35
| <cite>Yaoi2007</cite>
|-
| [[GH76]]
| none
| (α/α)6
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00005agd pdb_00005agd]
| endo-α-1,6-mannanase
| ''Bacillus circulans''
| α-1,6-mannopentaose
| '''Asp125'''
| Asp124
| <cite>Thompson2015</cite>
|-
| [[GH77]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002oww pdb_00002oww]
| 4-α-glucanotransferase
| ''Thermus thermofilus''
| acarbose + 4-deoxy-α-{{Smallcaps|d}}-glucose
| '''Glu340'''
| Asp293
| <cite>Barends2007</cite>
|-
| [[GH78]]
| H
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00003w5n pdb_00003w5n]
| α-{{Smallcaps|l}}-rhamnosidase
| ''Streptomyces avermitilis''
| {{Smallcaps|l}}-rhamnose
| '''Glu636'''
| Glu895
| <cite>Fujimoto2013</cite>
|-
| [[GH79]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00005e9c pdb_00005e9c]
| heparanase
| ''Homo sapiens''
| heparin tetrasaccharide
| '''Glu225'''
| Glu343
| <cite>Wu2015</cite>
|-
| [[GH80]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH24''
|
|
|
|
|
|
|-
| [[GH81]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00005t4g pdb_00005t4g]
| endo-β-1,3-glucanase
| ''Bacillus halodurans'' C-125
| laminarin
| '''Asp466'''
| Glu542
| <cite>Pluvinage2017</cite>
|-
| [[GH83]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001z4x pdb_00001z4x]
| hemagglutinin-neuraminidase
| Simian virus 5
| α-2,3-sialyllactose
| '''Asp187''' on flexible loop
| Tyr523 (with Glu390)
| <cite>Yuan2005</cite>
|-
| [[GH84]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002chn pdb_00002chn]
| β-''N''-acetyl-glucosaminidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| NAG-thiazoline
| '''Glu242'''
| internal
| <cite>Dennis2006</cite>
|-
| [[GH85]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002w92 pdb_00002w92]
| endo-β-''N''-acetyl-glucosaminidase D
| ''Streptococcus pneumoniae'' TIGR4
| NAG-thiazoline
| '''Glu337'''
| internal
| <cite>Abbott2009</cite>
|-
| [[GH86]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00004aw7 pdb_00004aw7]
| β-porphyranase
| ''Bacteroides plebeius''
| porphyran fragment
| '''Glu152'''
| Glu279
| <cite>Hehemann_1_2012</cite>
|-
| [[GH89]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002vcb pdb_00002vcb]
| α-''N''-acetyl-glucosaminidase
| ''Clostridium perfringens''
| PUGNAc
| '''Glu483'''
| Glu601
| <cite>Ficko-Blean2008</cite>
|-
| [[GH92]]
| none
| (α/α)6 and β-sandwich
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00002ww1 pdb_00002ww1]
| α-1,2-mannosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| thiomannobioside
| '''Glu533'''
| Asp644 Asp642
| <cite>Zhu2009</cite>
|-
| [[GH93]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00003a72 pdb_00003a72]
| exo-arabinanase
| ''Penicillium chrysogenum''
| arabinobiose
| '''Glu246'''
| Glu174
| <cite>Sogabe2011</cite>
|-
| [[GH94]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00004zli pdb_00004zli]
| cellobionic acid phosphorylase
| ''Saccharophagus degradans''
| 3-O-β-{{Smallcaps|d}}-glucopyranosyl-α-{{Smallcaps|d}}-glucopyranuronic acid
| '''Asp472'''
| phosphate
| <cite>Nam2015</cite>
|-
| [[GH95]]
| none
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00002ead pdb_00002ead]
| α-1,2-{{Smallcaps|l}}-fucosidase
| ''Bifidobacterium bifidum''
| Fuc-α-1,2-Gal
| '''Glu566'''
| Asn423 Asp766
| <cite>Nagae2007</cite>
|-
| [[GH97]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining + inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00002zq0 pdb_00002zq0]
| α-glucosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| acarbose
| '''Glu532'''
| Glu508
| <cite>Kitamura2008</cite>
|-
| [[GH98]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00002wmg pdb_00002wmg]
| endo-β-1,4-galactosidase
| ''Streptococcus pneumoniae''
| A-LewisY pentasaccharide
| '''Glu158'''
| Asp251 Glu301
| <cite>Higgins2009</cite>
|-
| [[GH99]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00004ad4 pdb_00004ad4]
| endo-α-mannosidase
| ''Bacteroides xylanisolvens''
| glucose-1,3-isofagomine and α-1,2- mannobiose
| '''Glu336'''
| debated
| <cite>Thompson2012</cite>
|-
| [[GH100]]
| G
| (α/α)6 core
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00005gop pdb_00005gop]
| invertase
| ''Anabaena (Nostoc) sp.'' pcc7120
| sucrose
| '''Asp188'''
| Glu414
| <cite>Xie2016</cite>
|-
| [[GH101]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00005a56 pdb_00005a56]
| endo-α-N-acetylgalactosaminidase
| ''Streptococcus pneumoniae'' TIGR4
| β-{{Smallcaps|d}}-Galp-(1-3)-α-{{Smallcaps|d}}-GalpNAc-(1)-methyl
| '''Glu796''' +water
| Asp764
| <cite>Gregg2015</cite>
|-
| [[GH102]]
| none
| double-ψ β-barrel
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00002pi8 pdb_00002pi8]
| lytic transglycosylase A
| ''Escherichia coli''
| chitohexaose
| '''Asp308'''
| none
| <cite>van_Straaten2007</cite>
|-
| [[GH103]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00001d0k pdb_00001d0k]
| lytic transglycosylase SLT35
| ''Escherichia coli''
| murodipeptides
| '''Glu162'''
| internal
| <cite>van_Asselt2000</cite>
|-
| [[GH106]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00005mwk pdb_00005mwk]
| α-{{Smallcaps|l}}-rhamnosidase BT_0986
| ''Bacteroides thetaiotaomicron''
| pectin heptasaccharide
| '''Glu461'''
| Glu593 or Glu561
| <cite>Ndeh2017</cite>
|-
| [[GH107]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| ''predicted syn by clan''
| ''see at GH29''
|
|
|
|
|
|
|-
| [[GH109]]
| none
| Rossmann fold
| alpha-{{Smallcaps|d}} or beta-{{Smallcaps|d}}
| resp. retaining or inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00006t2b pdb_00006t2b]
| α/β-N-acetylgalactosaminidase
| ''Akkermansia muciniphila''
| α-{{Smallcaps|d}}-GalpNAc
| '''His404''' (relay from Asp408)
| not applicable
| <cite>Teze2020</cite>
|-
| [[GH110]]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00007jwf pdb_00007jwf]
| α-1,3-galactosidase
| ''Pseudoalteromonas distincta''
| Gal-α1,3-Gal
| '''Asp344'''
| Asp321 Asp345
| <cite>McGuire2020</cite>
|-
| [[GH113]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00004cd8 pdb_00004cd8]
| β-mannanase
| ''Alicyclobacillus acidocaldarius''
| mannobioimidazole
| '''Glu151'''
| Glu231
| <cite>Williams2014</cite>
|-
| [[GH116]]
| O
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''perpendicular''''' (anomaly)
| [{{PDBlink}}pdb_00008i5u pdb_00008i5u]
| β-glucosidase
| ''Thermoanaerobacterium xylanolyticum'' LX-11
| laminaribiose
| '''Asp593'''
| Glu441
| <cite>Pengthaisong2023</cite>
|-
| [[GH117]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00004ak7 pdb_00004ak7]
| α-1,3-3,6-anhydro-{{Smallcaps|l}}-galactosidase
| ''Bacteroides plebeius''
| neoagarobiose
| '''His302''' (relay from Asp320)
| Asp90
| <cite>Hehemann_2_2012</cite>
|-
| [[GH119]]
| T
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at GH57''
|
|
|
|
|
|
|-
| [[GH120]]
| none
| parallel β-helix and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00003vsv pdb_00003vsv]
| β-xylosidase XylC
| ''Thermoanaerobacterium saccharolyticum'' JW/SL-YS485
| {{Smallcaps|d}}-xylose
| '''Glu405'''
| Asp382
| <cite>Huang2012</cite>
|-
| [[GH123]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00005fr0 pdb_00005fr0]
| exo-β-N-acetyl-galactosaminidase
| ''Clostridium perfringens''
| ''N''-difluoroacetyl-{{Smallcaps|d}}-galactosamine
| '''Glu345'''
| internal
| <cite>Noach2016</cite>
|-
| [[GH124]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00006g1i pdb_00006g1i]
| endo-β-1,4-glucanase
| ''Acetivibrio thermocellus'' ATCC 27405
| fructosylated cellopentaose
| '''Glu203'''
| unknown
| <cite>Urresti2018</cite>
|-
| [[GH125]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00005m7y pdb_00005m7y]
| exo-α-1,6-mannosidase
| ''Clostridium perfringens''
| 1,6-α-mannotriose
| '''Asp220'''
| Glu393
| <cite>Alonso-Gil2016</cite>
|-
| [[GH127]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00003wrg pdb_00003wrg]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bifidobacterium longum''
| {{Smallcaps|l}}-arabinose
| '''Glu322'''
| Cys417
| <cite>Huang2014</cite>
|-
| [[GH128]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00006ufl pdb_00006ufl]
| β-1,3-glucanase
| ''Amycolatopsis mediterranei''
| laminarihexaose
| '''Glu102'''
| Glu199
| <cite>Santos2020</cite>
|-
| [[GH129]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00005wzn pdb_00005wzn]
| exo-α-''N''-acetylgalactosaminidase (NagBb)
| ''Bifidobacterium bifidum'' JCM 1254
| GalNAc
| '''Glu478'''
| Asp435
| <cite>Sato2017</cite>
|-
| [[GH130]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00005b0s pdb_00005b0s]
| β-1,2-mannobiose phosphorylase
| ''Listeria innocua''
| β-1,2-mannotriose
| '''Asp141''' relay
| phosphate
| <cite>Tsuda2015</cite>
|-
| [[GH133]]
| none
| (α/α)6
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00005d0f pdb_00005d0f]
| glycogen-debranching enzyme
| ''Nakaseomyces glabratus'' CBS 138
| maltopentaose
| '''Glu564'''
| Asp535
| <cite>Zhai2016</cite>
|-
| [[GH134]]
| none
| β + α
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00005jug pdb_00005jug]
| β-mannanase
| ''Streptomyces sp.''
| mannopentaose
| '''Glu45'''
| Asp57
| <cite>Jin2016</cite>
|-
| [[GH135]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00005d6t pdb_00005d6t]
| α-1,4-galactosaminogalactan
| ''Aspergillus clavatus''
| β-{{Smallcaps|d}}-GalpNAc
| '''Glu222'''
| Asp166
| <cite>Bamford2015</cite>

|-

| [[GH136]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00005gqf pdb_00005gqf]
| lacto-N-biosidase
| ''Bifidobacterium longum''
| lacto-N-biose
| '''Asp411'''
| Asp418
| <cite>Yamada2017</cite>
|-
| [[GH137]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|l}}
| unknown
| '''''anti'''''
| [{{PDBlink}}pdb_00005mui pdb_00005mui]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0996
| ''Bacteroides thetaiotaomicron''
| pectin oligosaccharide
| '''Glu240'''
| Glu159
| <cite>Ndeh2017</cite>
|-
| [[GH138]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00006hzg pdb_00006hzg]
| α-1,2-{{Smallcaps|d}}-galacturonidase
| ''Bacteroides paurosaccharolyticus''
| alpha-{{Smallcaps|d}}-galactopyranuronic
| '''Glu294'''
| Glu361
| <cite>Labourel2019</cite>
|-
| [[GH140]]
| A
| (β/α)6
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH144]]
| S
| (α/α)8
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00008xul pdb_00008xul]
| beta-1,2-glucanase
| ''Xanthomonas campestris''
| beta-1,2-glucoheptasaccharide
| '''Glu239'''
| unknown
| <cite>Nakajima2024</cite>
|-
| [[GH146]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00005opj pdb_00005opj]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bacteroides thetaiotaomicron''
| {{Smallcaps|l}}-arabinose
| '''Glu320'''
| Cys416
| <cite>Luis2018</cite>
|-
| [[GH147]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH148]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH149]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH156]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00006s0e pdb_00006s0e]
| exo-α-sialidase
| uncultured bacterium pG7
| N-acetyl-2,3-dehydro-2-deoxyneuraminic acid
| '''His134''' (relay from Asp132)
| Asp14
| <cite>Bule2019</cite>
|-
| [[GH157]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH158]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH161]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH162]]
| S
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00006imw pdb_00006imw]
| endo-β-1,2-glucanase
| ''Talaromyces funiculosus''
| beta-1,2-glucan
| '''Glu262''' via C3-OH of glc at subs. +2
| Asp446
| <cite>Tanaka2019</cite>
|-
| [[GH164]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00006t75 pdb_00006t75]
| β-mannosidase
| ''Bacteroides salyersiae''
| 2-deoxy-2-F-mannosyl
| '''Glu160'''
| Glu297
| <cite>Armstrong2020</cite>
|-
| [[GH167]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|

|

|
|-
| [[GH168]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00008ya7 pdb_00008ya7]
| endo-α-1,3-{{Smallcaps|l}}-fucanase (Fun168A)
| ''Wenyingzhuangia fucanilytica'' CZ1127
| sulfated fucotetraose
| '''Glu264'''
| Asp206
| <cite>Chen2024</cite>
|-
| [[GH169]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH172]]
| none
| β-jelly roll
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00007v1w pdb_00007v1w]
| difructose-anhydride synthase
| ''Bifidobacterium dentum''
| beta-{{Smallcaps|d}}-arabinofuranose
| '''Glu270'''
| Glu291
| <cite>Kashima2021</cite>
|-
| [[GH173]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH178]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at e.g. GH15''
|
|
|
|
|
|
|-
| [[GH181]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00008axi pdb_00008axi]
| exo-α-sialidase
| ''Akkermansia muciniphila''
| 2-deoxy-2,3-dehydro-''N''-acetyl-neuraminic acid + T-antigen disaccharide
| '''Asp345'''
| Glu218
| <cite>Shuoker2023</cite>
|-
| [[GH183]]
| none
| 5-bladed β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00008ic1 pdb_00008ic1]
| endo-α-1,5-{{Smallcaps|d}}-arabinofuranosidase
| ''Microbacterium arabinogalactanolyticum'' JCM 9171
| α-{{Smallcaps|d}}-Araf-(1,5)-α-{{Smallcaps|d}}-Araf-(1,5)-α-{{Smallcaps|d}}-Araf-(1,5)-α-{{Smallcaps|d}}-Araf
| '''Asp51'''
| Asp33
| <cite>Shimokawa2023</cite>
|-
| [[GH186]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00008ip1 pdb_00008ip1]
| β-1,2-glucanase
| ''Escherechia coli''
| β-1,2-glucan
| '''Asp388'''
| Asp300 + 3 waters
| <cite>Motouchi2023</cite>
|-
| [[GH192]]
| S
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at e.g. GH144''
|
|
|
|
|
|
|-
| [[GH193]]
| S
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at e.g. GH144''
|
|
|
|
|
|
|-
| [[GH194]]
| S
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at e.g. GH144''
|
|
|
|
|
|
|-
| [http://www.cazy.org/GH0.html n.c.*]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00002vjj pdb_00002vjj]
| endo-α-N-acetylglucosaminidase
| Bacteriophage HK620
| O18A1 O-antigen hexasaccharide
| '''Asp339'''
| Glu372
| <cite>Barbirz2008</cite>
|}
<nowiki>*</nowiki> n.c.: Found among the collection of [http://www.cazy.org/GH0.html non-classified GH sequences in the CAZy Database].

== References ==

<biblio>
# HeightmanVasella1999 Heightman TD and Vasella AT. ''Recent Insights into Inhibition, Structure, and Mechanism of Configuration-Retaining Glycosidases.'' Angew Chem Int Ed. 1999 38(6):750-770. [http://www3.interscience.wiley.com/journal/55000581/abstract Article online].
# Nerinckx2005 pmid=15642336
# Wu2012 pmid=23137336
# Perez1978 Pérez S and Marchessault RH. ''The exo-anomeric effect: experimental evidence from crystal structures.'' Carbohydr res. 1978 65:114-120. [http://dx.doi.org/10.1016/S0008-6215(00)84218-4 DOI:10.1016/S0008-6215(00)84218-4]
# Cramer1997 Cramer CJ, Truhlar DG, and French AD. ''Exo-anomeric effects on energies and geometries of different conformations of glucose and related systems in the gas phase and aqueous solution.'' Carbohydr res. 1997 298:1-14. [http://dx.doi.org/10.1016/S0008-6215(96)00297-2 DOI:10.1016/S0008-6215(96)00297-2]
# Johnson2009 pmid=19733839
# Alonso2016 pmid=26889578
# Gloster2006 pmid=17002288
# van_Bueren2009 pmid=18976664
# Hrmova2001 pmid=11709165
# Rajan2004 pmid=15341727
# Varrot2003 pmid=12595701
# Zhou1999 pmid=10508787
# Sulzenbacher1999 pmid=10200171
# Urbanikova2011 pmid=21501386
# Guerin2002 pmid=11884144
# Schubot2004 pmid=14756552
# Suzuki2009 pmid=19279191
# Wan2014 pmid=24419374
# Sandgren2004 pmid=15364577
# Uitdehaag1999 pmid=10331869
# Miyake2003 pmid=12741813
# Harris1993 pmid=8431441
# Allouch2004 pmid=15062085
# Wojtkowiak2013 pmid=23275163
# Papanikolau2001 pmid=11560481
# Prag2000 pmid=10884356
# Vocadlo2001 pmid=11518970
# Karlsen1996 pmid=15299731
# Baldwin1993 pmid=8259514
# Cartmell2008 pmid=18799462
# Fernandez-Leiro2010 pmid=20592022
# Abbott2007 pmid=17397864
# Sakurama2012 pmid=22451675
# Sim2008 pmid=18036614
# Verhaest2007 pmid=17335500
# Amaya2004 pmid=15130470
# Zhu2012 pmid=23015718
# Maksimainen2011 pmid=21130883
# Merceron2012 pmid=23012371
# Gibson2007 pmid=17455176
# Shah2008 pmid=18599462
# Czjzek2005 pmid=16212978
# Godoy2016 pmid=27685756
# Fujimoto2010 pmid=20739278
# Kitago2007 pmid=17905739
# Davies1996 pmid=15299721
# Lyu2014 pmid=24766439
# Karaveg2005 pmid=15713668
# Nerinckx2008 pmid=18619586
# Pluvinage2013 pmid=23921382
# Yuan2005 pmid=15893670
# Hoevel2003 pmid=14517232
# Espina2014 pmid=24816105
# Le_Nours2009 pmid=19089956
# Miyanaga2004 pmid=15292273
# Bianchetti2015 pmid=25752603
# Markovic-Housley2000 pmid=11080624
# Imamura2003 pmid=12618437
# Hill2013 pmid=24297913
# Maehara2014 pmid=24482228
# Miyazaki2016 pmid=27688023
# Touhara2014 pmid=24828502
# Suzuki2016 pmid=26494689
# Golan2004 pmid=14573597
# Meng2003 pmid=14517548
# Ito2011 pmid=21354427

# Mazurkewich2025 pmid=40877455

# Hurtado-Gerrero2009 pmid=19097997

# Yaoi2007 pmid=17498741
# Martinez-Caballero2023 pmid=37418323
# Thompson2015 pmid=25772148
# Barends2007 pmid=17420245
# Fujimoto2013 pmid=23486481
# Wu2015 pmid=26575439
# Pluvinage2017 pmid=28781080
# Dennis2006 pmid=16565725
# Abbott2009 pmid=19181667
# Hehemann_1_2012 pmid=23150581
# Ficko-Blean2008 pmid=18443291
# Zhu2009 pmid=20081828
# Sogabe2011 pmid=21543843
# Nam2015 pmid=26041776
# Nagae2007 pmid=17459873
# Kitamura2008 pmid=18981178
# Higgins2009 pmid=19608744
# van_Straaten2007 pmid=17502382
# van_Asselt2000 pmid=10684641
# Ndeh2017 pmid=28329766
# Labourel2019 pmid=30877196
# Nakajima2024 Nakajima M. et al. ''Extensive distribution of β-1,2-glucanases: finding of new glycoside hydrolase families of β-1,2-glucanases.'' BioRxiv preprint 2024. https://doi.org/10.1101/2024.02.06.578578
# Luis2018 pmid=29255254
# Bule2019 pmid=31645552
# Jin2016 Jin Y, Petricevic M, John A, Raich L, Jenkins H, Portela De Souza L, Cuskin F, Gilbert HJ, Rovira C, Goddard-Borger ED, Williams SJ, and Davies GJ. ''A β-Mannanase with a Lysozyme-like Fold and a Novel Molecular Catalytic Mechanism.'' ACS Cent Sci. 2016 Nov [http://dx.doi.org/10.1021/acscentsci.6b00232 DOI:10.1021/acscentsci.6b00232]
# Yamada2017 pmid=28392148

# Bamford2015 pmid=26342082

# Ohnuma2014 pmid=24582745

# Thompson2012 pmid=22219371
# Xie2016 pmid=27777307
# Gregg2015 pmid=26304114
# Williams2014 pmid=24339341
# Pengthaisong2023 pmid=37180965
# Hehemann_2_2012 pmid=22393053
# Huang2012 pmid=22992047
# Noach2016 pmid=27038508
# Urresti2018 pmid=30084399
# Alonso-Gil2016 pmid=28026180
# Huang2014 Huang CH, Zhu Z, Cheng YS, Chan HC, Ko TP, Chen CC, Wang I, Ho MR, Hsu ST, Zeng YF, Huang YN, Liu JR, Guo RT. ''Structure and Catalytic Mechanism of a Glycoside Hydrolase Family-127 β-L-Arabinofuranosidase (HypBA1).'' J Bioprocess Biotech. 2014 4:171 [http://dx.doi.org/10.4172/2155-9821.1000171 DOI:10.4172/2155-9821.1000171]
# Tsuda2015 pmid=26632508
# Zhai2016 pmid=27088557
# Barbirz2008 pmid=18547389
# Tanaka2019 pmid=30926603
# Armstrong2020 pmid=31871050
# Chen2024 pmid=38795894
# Santos2020 pmid=32451508
# Sato2017 pmid=28546425
# Kashima2021 pmid=34688653

# Teze2020 Teze D, Shuoker B, Chaberski EK, Kunstmann S, Fredslund F, Nielsen TS, Stender EGP, Peters GHJ, Karlsson EN, Welner DS, Hachem MA. ''The Catalytic Acid–Base in GH109 Resides in a Conserved GGHGG Loop and Allows for Comparable α-Retaining and β-Inverting Activity in an N-Acetylgalactosaminidase from Akkermansia muciniphila.'' ACS Catal. 2020, 10, 3809−3819 [https://dx.doi.org/10.1021/acscatal.9b04474 DOI:10.1021/acscatal.9b04474]

# McGuire2020 pmid=33127644

# Shuoker2023 pmid=37005422
# Shimokawa2023 pmid=37726269
# Motouchi2023 pmid=37735577
</biblio>
[[Category:Definitions and explanations]]

Syn/anti lateral protonation

2026-04-16T12:04:48Z

Wim Nerinckx: added example for GH71, GH109 and GH135

{{CuratorApproved}}
* [[Author]]: [[User:Wim Nerinckx|Wim Nerinckx]]
* [[Responsible Curator]]: [[User:Spencer Williams|Spencer Williams]]

----

== Overview ==

This page provides a table that summarizes the spatial positioning of the catalytic [[general acid]] residue in the active sites of [[glycoside hydrolase]]s, relative to the substrate. The table below updates those found in the seminal paper on this concept by Heightman and Vasella <cite>HeightmanVasella1999</cite>, and a following paper by Nerinckx ''et al.'' <cite>Nerinckx2005</cite>.

== Background ==

The ''"not from above, but from the side"'' concept of semi-lateral glycosidic oxygen [[General_acid/base|protonation]] by [[glycoside hydrolase]]s was introduced by Heightman and Vasella <cite>HeightmanVasella1999</cite>. It was originally only described for [[Anomeric centre (alpha and beta)|beta]]-equatorial [[glycoside hydrolase]]s, but appears to be equally applicable to enzymes acting on an [[Anomeric centre (alpha and beta)|alpha]]-axial glycosidic bond <cite>Nerinckx2005</cite>. When dividing [[Sub-site nomenclature|subsite -1]] into half-spaces by a plane defined by the glycosidic oxygen and C1' and H1' of the –1 glycoside, many ligand-complexed structures reveal that the [[General_acid/base|proton donor]] is positioned either in the ''syn'' half-space (near the ring-oxygen of the –1 glycoside), or in the ''anti'' half-space (on the opposite side of the ring-oxygen). Members of the same GH [[Families|family]] appear to share a common ''syn'' or ''anti'' [[General_acid/base|protonator]] arrangement and further, this specificity appears to be preserved within [[Clans|Clans]] of [[Families|families]]. This page's compilation of [[Sub-site nomenclature|subsite -1]] occupied complexes shows that about 70% of all GH [[Families|families]] are ''anti'' [[General_acid/base|protonators]].

Closer inspection of crystal structures of [[Sub-site nomenclature|–1/+1 subsite]]-spanning substrates, or substrate-analogue ligands, in complex with enzymes reveals a further intriguing corollary <cite>Nerinckx2005 Wu2012</cite>. In substrate-bound complexes with ''anti'' [[General_acid/base|protonating]] GH enzymes, the scissile [[Anomeric centre (alpha and beta)|anomeric bond]] (often studied using the thio-analogue) shows a dihedral angle φ (O5'-C1'-[O,S]x-Cx) that is in the lowest-energy synclinal (gauche) conformation. The rationale for this is that a minus synclinal dihedral angle φ for an equatorial glycosidic bond, or plus synclinal for an axial glycosidic bond <cite>Perez1978</cite>, allows for hyperconjugative overlap of the C1'-O5' antibonding orbital with an antiperiplanar-oriented lone pair orbital lobe of the glycosidic oxygen, thereby creating partial double bond character and stabilization of the glycosidic bond by 4–5 kcal/mol; this ground-state stabilizing phenomenon is known as the ‘exo-anomeric effect’ <cite>Cramer1997 Johnson2009 Alonso2016</cite>. ''Anti'' [[General_acid/base|protonation]] occurs on the glycosidic oxygen’s antiperiplanar lone pair, thereby removing the stabilizing exo-anomeric effect. This suggests that ''anti'' [[General_acid/base|protonation]] is an enzymic approach for lowering the activation barrier leading to the [[Transition state|transition state]] (Figure 1 centre).

''Syn'' [[General_acid/base|protonating]] [[glycoside hydrolase]]s apparently make use of a different approach <cite>Nerinckx2005 Wu2012</cite>. In many [[Sub-site nomenclature|–1/+1 subsite]]-spanning ligand complexes, the dihedral angle φ of the scissile anomeric bond has been rotated away from its lowest-energy synclinal position: clockwise to minus-anticlinal or antiperiplanar for beta-equatorial; counterclockwise to plus-anticlinal or antiperiplanar for alpha-axial [[Anomeric centre (alpha and beta)|anomeric bonds]]. This removes the hyperconjugative overlap and thus also the stabilizing exo-anomeric effect. And because of this rotation, a lone pair of the glycosidic oxygen is directed into the ''syn'' half-space, allowing it to be protonated by the ''syn''-positioned [[General_acid/base|proton donor]] (Figure 1 right).

[[File:Syn_anti.jpg|800px|thumb|center|Figure 1. Newman projections, with the glycosidic oxygen as proximal atom and the anomeric carbon as distal atom, showing ''anti'' (centre) versus ''syn'' (right) semi-lateral [[General_acid/base|protonation]] in beta-equatorial (top) and alpha-axial (bottom) [[glycoside hydrolase]]s. The indicated φ is the dihedral angle for O5'-C1'-O4-C4.]]

== Table of ''syn/anti'' protonation examples ==

This table contains only one example per GH [[Families|family]] of a ligand-complexed protein structure where the ''syn'' or ''anti'' positioning of the [[General_acid/base|proton donor]] can be clearly observed; other examples may be available on a [[Families|family-by-family]] basis. The reader is thus advised to consult the [http://www.cazy.org/fam/acc_GH.html#table CAZy database] for a current, comprehensive list of CAZyme structures. Where available, the selected examples are Michaelis-type complexes with the ligand spanning the [[Sub-site nomenclature|-1/+1 subsites]], since these have an intact glycosidic or thioglycosidic bond, or are ''N''-analogs of the substrate (''e.g.'' acarbose). In some examples, the [[General_acid/base|proton donor]] has been mutated (''e.g.'', to the corresponding amide or to an alanine), and in those cases one may wish to look at a superposition of the given PDB example with the structure of the native enzyme. If a Michaelis-type complex is not yet available, the second and third example choices, respectively, are trapped glycosyl-enzyme [[intermediate]]s and product complexes where [[Sub-site nomenclature|subsite -1]] is occupied.

''Please also be aware that this is a large table with many data. Please contact the page Author or Responsible Curator with corrections.''

=== Table ===
This table can be re-sorted by clicking on the icons in the header (''javascript must be turned on in your browser''). To reset the page to be sorted by GH family, click the ''View'' tab at the very top of the page.

{| {{Prettytable}} class="sortable"
|- valign="top"
! '''Family'''
! '''Clan'''
! '''Structure fold '''
! '''Anomeric specificity'''
! '''Mechanism'''
! '''''Syn/anti'' protonator'''
! '''Example PDB ID'''
! '''Enzyme'''
! '''Organism'''
! '''Ligand'''
! '''General acid'''
! '''Nucleophile or General base'''
! '''Reference'''
|-
| [[GH1]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002cer pdb_00002cer]
| β-glycosidase S
| ''Sulfolobus solfataricus'' P2
| phenethyl glucoimidazole
| '''Glu206'''
| Glu387
| <cite>Gloster2006</cite>
|-
| [[GH2]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002vzu pdb_00002vzu]
| exo-β-glucosaminidase
| ''Amicolatopsis orientalis''
| PNP-β-{{Smallcaps|d}}-glucosamine
| '''Glu469'''
| Glu541
| <cite>van_Bueren2009</cite>
|-
| [[GH3]]
| none
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001iex pdb_00001iex]
| exo-1,3-1,4-glucanase
| ''Hordeum vulgare''
| thiocellobiose
| '''Glu491'''
| Asp285
| <cite>Hrmova2001</cite>
|-
| [[GH4]]
| none
| Rossmann + α6/β3 + β3/α4
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001u8x pdb_00001u8x]
| 6-P-α-glucosidase
| ''Bacillus subtilis''
| alpha-{{Smallcaps|d}}-glucose-6-phosphate
| '''Asp172'''
| not applicable
| <cite>Rajan2004</cite>
|-
| [[GH5]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001h2j pdb_00001h2j]
| endo-β-1,4-glucanase
| ''Bacillus agaradhaerens''
| 2',4'-DNP-2-F-cellobioside
| '''Glu129'''
| Glu228
| <cite>Varrot2003</cite>
|-
| [[GH6]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00001qjw pdb_00001qjw]
| cellobiohydrolase 2
| ''Hypocrea jecorina''
| (Glc)2-S-(Glc)2
| '''Asp221'''
| debated
| <cite>Zhou1999</cite>
|-
| [[GH7]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00001ovw pdb_00001ovw]
| endo-1,4-glucanase
| ''Fusarium oxysporum''
| thio-(Glc)5
| '''Glu202'''
| Glu197
| <cite>Sulzenbacher1999</cite>
|-
| [[GH8]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00001kwf pdb_00001kwf]
| endo-1,4-glucanase
| ''Clostridium thermocellum''
| cellopentaose
| '''Glu95'''
| Asp278
| <cite>Guerin2002</cite>
|-
| [[GH9]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00001rq5 pdb_00001rq5]
| cellobiohydrolase
| ''Clostridium thermocellum''
| cellotetraose
| '''Glu795'''
| Asp383
| <cite>Schubot2004</cite>
|-
| [[GH10]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002d24 pdb_00002d24]
| β-1,4-xylanase
| ''Streptomyces olivaceoviridis'' E-86
| xylopentaose
| '''Glu128'''
| Glu236
| <cite>Suzuki2009</cite>
|-
| [[GH11]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00004hk8 pdb_00004hk8]
| endo-β-1,4-xylanase
| ''Hypocrea jecorina''
| xylohexaose
| '''Glu177'''
| Glu86
| <cite>Wan2014</cite>
|-
| [[GH12]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00001w2u pdb_00001w2u]
| endoglucanase
| ''Humicola grisea''
| thiocellotetraose
| '''Glu205'''
| Glu120
| <cite>Sandgren2004</cite>
|-
| [[GH13]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001cxk pdb_00001cxk]
| β-cyclodextrin glucanotransferase
| ''Bacillus circulans''
| maltononaose
| '''Glu257'''
| Asp229
| <cite>Uitdehaag1999</cite>
|-
| [[GH14]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00001itc pdb_00001itc]
| β-amylase
| ''Bacillus cereus''
| maltopentaose
| '''Glu172'''
| Glu367
| <cite>Miyake2003</cite>
|-
| [[GH15]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00001dog pdb_00001dog]
| glucoamylase
| ''Aspergillus awamori''
| 1-deoxynojirimycin
| '''Glu179'''
| Glu400
| <cite>Harris1993</cite>
|-
| [[GH16]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00001urx pdb_00001urx]
| β-agarase A
| ''Zobellia galactanivorans''
| oligoagarose
| '''Glu152'''
| Glu147
| <cite>Allouch2004</cite>
|-
| [[GH17]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00004gzj pdb_00004gzj]
| endo-β-1,3-glucanase
| ''Solanum tuberosum''
| laminaratriose + laminarabiose
| '''Glu118'''
| Glu259
| <cite>Wojtkowiak2013</cite>
|-
| [[GH18]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001ffr pdb_00001ffr]
| chitinase A
| ''Serratia marcescens''
| (NAG)6
| '''Glu315'''
| internal
| <cite>Papanikolau2001</cite>
|-
| [[GH19]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00003wh1 pdb_00003wh1]
| chitinase
| ''Bryum coronatum''
| (GlcNAc)4
| '''Glu61'''
| Glu70
| <cite>Ohnuma2014</cite>
|-
| [[GH20]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001c7s pdb_00001c7s]
| chitobiase
| ''Serratia marcescens''
| chitobiose
| '''Glu540'''
| internal
| <cite>Prag2000</cite>
|-
| [[GH22]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00001h6m pdb_00001h6m]
| lysozyme C
| ''Gallus gallus''
| Chit-2-F-chitosyl
| '''Glu35'''
| Asp52
| <cite>Vocadlo2001</cite>
|-
| [[GH23]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00001lsp pdb_00001lsp]
| lysozyme G
| ''Cygnus atratus''
| Bulgecin A
| '''Glu73'''
| internal
| <cite>Karlsen1996</cite>
|-
| [[GH24]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_0000148l pdb_0000148l]
| lysozyme E
| Bacteriophage T4
| chitobiosyl
| '''Glu11'''
| Glu26
| <cite>Baldwin1993</cite>
|-
| [[GH26]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002vx6 pdb_00002vx6]
| exo-β-mannanase
| ''Cellvibrio japonicus'' Ueda107
| Gal1Man4
| '''Glu221'''
| Glu338
| <cite>Cartmell2008</cite>
|-
| [[GH27]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}} / beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00003lrm pdb_00003lrm]
| α-galactosidase
| ''Saccharomyces cerevisiae''
| raffinose
| '''Asp209'''
| Asp141
| <cite>Fernandez-Leiro2010</cite>
|-
| [[GH28]]
| N
| β-helix
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00002uvf pdb_00002uvf]
| exo-polygalacturonosidase
| ''Yersinia enterocolitica'' ATCC9610D
| digalacturonic acid
| '''Asp402'''
| Asp381 Asp403
| <cite>Abbott2007</cite>
|-
| [[GH29]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00003uet pdb_00003uet]
| α-1,3/4-fucosidase
| ''Bifidobacterium longum'' subsp. infantis
| lacto-''N''-fucopentaose II
| '''Glu217'''
| Asp172
| <cite>Sakurama2012</cite>
|-
| [[GH30]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002y24 pdb_00002y24]
| glucurono-xylanase
| ''Dickea chrysanthemi'' D1
| glucuronoxylan tetrasaccharide
| '''Glu165'''
| Glu253
| <cite>Urbanikova2011</cite>
|-
| [[GH31]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002qmj pdb_00002qmj]
| maltase-glucoamylase
| ''Homo sapiens''
| acarbose
| '''Asp542'''
| Asp443
| <cite>Sim2008</cite>
|-
| [[GH32]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002add pdb_00002add]
| fructan β-(2,1)-fructosidase
| ''Cichorium intybus''
| sucrose
| '''Glu201'''
| Asp22
| <cite>Verhaest2007</cite>
|-
| [[GH33]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001s0i pdb_00001s0i]
| transsialidase
| ''Trypanosoma cruzi''
| sialyllactose
| '''Asp59'''
| Tyr342 (with Glu230)
| <cite>Amaya2004</cite>
|-
| [[GH34]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00004gzw pdb_00004gzw]
| N2 neuraminidase
| ''Influenza'' A Tanzania/205/2010 H3N2
| α-{{Smallcaps|d}}-Neup5Ac-(2,3)-β-{{Smallcaps|d}}-Galp-(1,4)-β-{{Smallcaps|d}}-GlcpNAc
| '''Asp151'''
| Tyr406 (with Glu277)
| <cite>Zhu2012</cite>
|-
| [[GH35]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00003ogv pdb_00003ogv]
| β-galactosidase
| ''Hypocrea jecorina''
| 2-phenylethyl 1-thio-β-{{Smallcaps|d}}-galactopyranoside
| '''Glu200'''
| Glu298
| <cite>Maksimainen2011</cite>
|-
| [[GH36]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00004fnu pdb_00004fnu]
| β-galactosidase
| ''Geobacillus stearothermophilus''
| stachyose
| '''Asp584'''
| Asp478
| <cite>Merceron2012</cite>
|-
| [[GH37]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00002jf4 pdb_00002jf4]
| trehalase
| ''Escherichia coli''
| validoxylamine
| '''Asp312'''
| Glu496
| <cite>Gibson2007</cite>
|-
| [[GH38]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00003czn pdb_00003czn]
| Golgi α-mannosidase II
| ''Drosophila melanogaster''
| GlcNAcMan(5)GlcNAc(2)
| '''Asp341'''
| Asp204
| <cite>Shah2008</cite>
|-
| [[GH39]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002bfg pdb_00002bfg]
| β-xylosidase
| ''Geobacillus stearothermophilus''
| 2,5-dinitrophenyl-β-{{Smallcaps|d}}-xyloside
| '''Glu160'''
| Glu278
| <cite>Czjzek2005</cite>
|-
| [[GH42]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00004ucf pdb_00004ucf]
| β-galactosidase
| ''Bifidobacterium bifidum''
| {{Smallcaps|d}}-galactose
| '''Glu161'''
| Glu320
| <cite>Godoy2016</cite>
|-
| [[GH43]]
| F
| 5-fold β-propeller
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00003akh pdb_00003akh]
| exo-1,5-α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces avermitilis''
| α-1,5-arabinofuranotriose
| '''Glu196'''
| Asp220
| <cite>Fujimoto2010</cite>
|-
| [[GH44]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002eqd pdb_00002eqd]
| endoglucanase
| ''Clostridium thermocellum''
| cellooctaose
| '''Glu186'''
| Glu359
| <cite>Kitago2007</cite>
|-
| [[GH45]]
| none
| 6-stranded β-barrel
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00004eng pdb_00004eng]
| endo-1,4-glucanase
| ''Humicola insolens''
| cellohexaose
| '''Asp121'''
| Asp10
| <cite>Davies1996</cite>
|-
| [[GH46]]
| I
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00004olt pdb_00004olt]
| chitosanase
| ''Microbacterium sp.'' OU01
| hexa-glucosamine
| '''Glu25'''
| Asp43
| <cite>Lyu2014</cite>
|-
| [[GH47]]
| none
| (α/α)7
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00001x9d pdb_00001x9d]
| α-mannosidase I
| ''Homo sapiens''
| Me-2-S-(α-Man)-2-thio-α-Man
| '''Asp463'''
| Glu599
| <cite>Karaveg2005</cite>, <cite>Nerinckx2008</cite>
|-
| [[GH48]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH8''
|
|
|
|
|
|
|-
| [[GH49]]
| N
| β-helix
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH28''
|
|
|
|
|
|
|-
| [[GH50]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00004bq5 pdb_00004bq5]
| exo-β-agarase
| ''Saccharophagus degradans''
| neoagarotetraose
| '''Glu535'''
| Glu695
| <cite>Pluvinage2013</cite>
|-
| [[GH51]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001qw9 pdb_00001qw9]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Geobacillus stearothermophilus''
| PNP-{{Smallcaps|l}}-arabinofuranoside
| '''Glu175'''
| Glu294
| <cite>Hoevel2003</cite>
|-
| [[GH52]]
| O
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| '' predicted perpendicular by clan, see at GH116''
| [{{PDBlink}}pdb_00004c1p pdb_00004c1p]
| β-xylosidase
| ''Geobacillus thermoglucosidasius''
| xylobiose
| '''Asp517'''
| Glu537
| <cite>Espina2014</cite>
|-
| [[GH53]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002ccr pdb_00002ccr]
| β-1,4-galactanase
| ''Bacillus licheniformis''
| galactotriose
| '''Glu165'''
| Glu263
| <cite>Le_Nours2009</cite>
|-
| [[GH54]]
| none
| β-sandwich
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001wd4 pdb_00001wd4]
| α-{{Smallcaps|l}}-arabinofuranosidase B
| ''Aspergillus kawachii''
| {{Smallcaps|l}}-arabinofuranose
| '''Asp297'''
| Glu221
| <cite>Miyanaga2004</cite>
|-
| [[GH55]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00004tz5 pdb_00004tz5]
| exo-β-1,3-glucanase
| ''Streptomyces sp.'' SirexAA-E
| laminarihexaose
| '''Glu502'''
| unknown
| <cite>Bianchetti2015</cite>
|-
| [[GH56]]
| none
| (β/α)7
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001fcv pdb_00001fcv]
| hyaluronidase
| ''Apis mellifera''
| (hyaluron.)4
| '''Glu113'''
| internal
| <cite>Markovic-Housley2000</cite>
|-
| [[GH57]]
| T
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001k1y pdb_00001k1y]
| glucanotransferase
| ''Thermococcus litoralis''
| acarbose
| '''Asp214'''
| Glu123
| <cite>Imamura2003</cite>
|-
| [[GH59]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00004ccc pdb_00004ccc]
| β-galactocerebrosidase
| ''Mus musculus''
| PNP-β-{{Smallcaps|d}}-galactoside
| '''Glu182'''
| Glu258
| <cite>Hill2013</cite>
|-
| [[GH62]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00003wn0 pdb_00003wn0]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces coelicolor''
| β-{{Smallcaps|l}}-Arabinofuranose
| '''Glu361'''
| Asp202
| <cite>Maehara2014</cite>
|-
| [[GH63]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00005ca3 pdb_00005ca3]
| α-glucosidase
| ''Escherichia coli''
| glucose and lactose
| '''Asp501'''
| Glu727
| <cite>Miyazaki2016</cite>
|-
| [[GH65]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00004ktr pdb_00004ktr]
| 2-O-α-glucosylglycerol phosphorylase
| ''Bacillus selenitireducens''
| isofagomine
| '''Glu475'''
| phosphate
| <cite>Touhara2014</cite>
|-
| [[GH66]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00005axh pdb_00005axh]
| dextranase
| ''Thermoanaerobacter pseudethanolicus''
| isomaltohexaose
| '''Glu374'''
| Asp312
| <cite>Suzuki2016</cite>
|-
| [[GH67]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00001l8n pdb_00001l8n]
| α-glucuronidase
| ''Geobacillus stearothermophilus''
| 4-O-methyl-{{Smallcaps|d}}-glucuronic acid and xylotriose
| '''Glu286'''
| Asp364 Glu392
| <cite>Golan2004</cite>
|-
| [[GH68]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001pt2 pdb_00001pt2]
| levansucrase
| ''Bacillus subtilis''
| sucrose
| '''Glu342'''
| Asp86
| <cite>Meng2003</cite>
|-
| [[GH70]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00003aic pdb_00003aic]
| glucansucrase
| ''Streptococcus mutans''
| α-acarbose
| '''Glu515'''
| Asp477
| <cite>Ito2011</cite>
|-
| [[GH71]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00009fnh pdb_00009fnh]
| endo-α-1,3-glucanase
| ''Aspergillus nidulans'' FGSC A4
| nigerotetraose
| '''Glu268'''
| Asp265
| <cite>Mazurkewich2025</cite>
|-
| [[GH72]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002w62 pdb_00002w62]
| β-1,3-glucanotransferase
| ''Saccharomyces cerevisiae'' S288C
| laminaripentaose
| '''Glu176'''
| Glu275
| <cite>Hurtado-Gerrero2009</cite>
|-
| [[GH73]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| unknown
| '''''syn'''''
| [{{PDBlink}}pdb_00007pod pdb_00007pod]
| peptidoglycan endo-β-1,4-''N''-acetylglucosaminidase
| ''Streptococcus pneumoniae'' R6
| NAG-NAM-NAG-NAM tetrasaccharide
| '''Glu585'''
| unknown
| <cite>Martinez-Caballero2023</cite>
|-
| [[GH74]]
| none
| 7-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00002ebs pdb_00002ebs]
| cellobiohydrolase (OXG-RCBH)
| ''Geotrichum sp.'' m128
| xyloglucan heptasaccharide
| '''Asp465'''
| Asp35
| <cite>Yaoi2007</cite>
|-
| [[GH76]]
| none
| (α/α)6
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00005agd pdb_00005agd]
| endo-α-1,6-mannanase
| ''Bacillus circulans''
| α-1,6-mannopentaose
| '''Asp125'''
| Asp124
| <cite>Thompson2015</cite>
|-
| [[GH77]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002oww pdb_00002oww]
| 4-α-glucanotransferase
| ''Thermus thermofilus''
| acarbose + 4-deoxy-α-{{Smallcaps|d}}-glucose
| '''Glu340'''
| Asp293
| <cite>Barends2007</cite>
|-
| [[GH78]]
| H
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00003w5n pdb_00003w5n]
| α-{{Smallcaps|l}}-rhamnosidase
| ''Streptomyces avermitilis''
| {{Smallcaps|l}}-rhamnose
| '''Glu636'''
| Glu895
| <cite>Fujimoto2013</cite>
|-
| [[GH79]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00005e9c pdb_00005e9c]
| heparanase
| ''Homo sapiens''
| heparin tetrasaccharide
| '''Glu225'''
| Glu343
| <cite>Wu2015</cite>
|-
| [[GH80]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH24''
|
|
|
|
|
|
|-
| [[GH81]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00005t4g pdb_00005t4g]
| endo-β-1,3-glucanase
| ''Bacillus halodurans'' C-125
| laminarin
| '''Asp466'''
| Glu542
| <cite>Pluvinage2017</cite>
|-
| [[GH83]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001z4x pdb_00001z4x]
| hemagglutinin-neuraminidase
| Simian virus 5
| α-2,3-sialyllactose
| '''Asp187''' on flexible loop
| Tyr523 (with Glu390)
| <cite>Yuan2005</cite>
|-
| [[GH84]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002chn pdb_00002chn]
| β-''N''-acetyl-glucosaminidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| NAG-thiazoline
| '''Glu242'''
| internal
| <cite>Dennis2006</cite>
|-
| [[GH85]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002w92 pdb_00002w92]
| endo-β-''N''-acetyl-glucosaminidase D
| ''Streptococcus pneumoniae'' TIGR4
| NAG-thiazoline
| '''Glu337'''
| internal
| <cite>Abbott2009</cite>
|-
| [[GH86]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00004aw7 pdb_00004aw7]
| β-porphyranase
| ''Bacteroides plebeius''
| porphyran fragment
| '''Glu152'''
| Glu279
| <cite>Hehemann_1_2012</cite>
|-
| [[GH89]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002vcb pdb_00002vcb]
| α-''N''-acetyl-glucosaminidase
| ''Clostridium perfringens''
| PUGNAc
| '''Glu483'''
| Glu601
| <cite>Ficko-Blean2008</cite>
|-
| [[GH92]]
| none
| (α/α)6 and β-sandwich
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00002ww1 pdb_00002ww1]
| α-1,2-mannosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| thiomannobioside
| '''Glu533'''
| Asp644 Asp642
| <cite>Zhu2009</cite>
|-
| [[GH93]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00003a72 pdb_00003a72]
| exo-arabinanase
| ''Penicillium chrysogenum''
| arabinobiose
| '''Glu246'''
| Glu174
| <cite>Sogabe2011</cite>
|-
| [[GH94]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00004zli pdb_00004zli]
| cellobionic acid phosphorylase
| ''Saccharophagus degradans''
| 3-O-β-{{Smallcaps|d}}-glucopyranosyl-α-{{Smallcaps|d}}-glucopyranuronic acid
| '''Asp472'''
| phosphate
| <cite>Nam2015</cite>
|-
| [[GH95]]
| none
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00002ead pdb_00002ead]
| α-1,2-{{Smallcaps|l}}-fucosidase
| ''Bifidobacterium bifidum''
| Fuc-α-1,2-Gal
| '''Glu566'''
| Asn423 Asp766
| <cite>Nagae2007</cite>
|-
| [[GH97]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining + inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00002zq0 pdb_00002zq0]
| α-glucosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| acarbose
| '''Glu532'''
| Glu508
| <cite>Kitamura2008</cite>
|-
| [[GH98]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00002wmg pdb_00002wmg]
| endo-β-1,4-galactosidase
| ''Streptococcus pneumoniae''
| A-LewisY pentasaccharide
| '''Glu158'''
| Asp251 Glu301
| <cite>Higgins2009</cite>
|-
| [[GH99]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00004ad4 pdb_00004ad4]
| endo-α-mannosidase
| ''Bacteroides xylanisolvens''
| glucose-1,3-isofagomine and α-1,2- mannobiose
| '''Glu336'''
| debated
| <cite>Thompson2012</cite>
|-
| [[GH100]]
| G
| (α/α)6 core
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00005gop pdb_00005gop]
| invertase
| ''Anabaena (Nostoc) sp.'' pcc7120
| sucrose
| '''Asp188'''
| Glu414
| <cite>Xie2016</cite>
|-
| [[GH101]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00005a56 pdb_00005a56]
| endo-α-N-acetylgalactosaminidase
| ''Streptococcus pneumoniae'' TIGR4
| β-{{Smallcaps|d}}-Galp-(1-3)-α-{{Smallcaps|d}}-GalpNAc-(1)-methyl
| '''Glu796''' +water
| Asp764
| <cite>Gregg2015</cite>
|-
| [[GH102]]
| none
| double-ψ β-barrel
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00002pi8 pdb_00002pi8]
| lytic transglycosylase A
| ''Escherichia coli''
| chitohexaose
| '''Asp308'''
| none
| <cite>van_Straaten2007</cite>
|-
| [[GH103]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00001d0k pdb_00001d0k]
| lytic transglycosylase SLT35
| ''Escherichia coli''
| murodipeptides
| '''Glu162'''
| internal
| <cite>van_Asselt2000</cite>
|-
| [[GH106]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00005mwk pdb_00005mwk]
| α-{{Smallcaps|l}}-rhamnosidase BT_0986
| ''Bacteroides thetaiotaomicron''
| pectin heptasaccharide
| '''Glu461'''
| Glu593 or Glu561
| <cite>Ndeh2017</cite>
|-
| [[GH107]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| ''predicted syn by clan''
| ''see at GH29''
|
|
|
|
|
|
|-
| [[GH109]]
| none
| Rossmann fold
| alpha-{{Smallcaps|d}} or beta-{{Smallcaps|d}}
| resp. retaining or inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00006t2b pdb_00006t2b]
| a/β-N-acetylgalactosaminidase
| ''Akkermansia muciniphila''
| α-{{Smallcaps|d}}-GalpNAc
| '''His404''' (relay from Asp408)
| not applicable
| <cite>Teze2020</cite>
|-
| [[GH110]]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00007jwf pdb_00007jwf]
| α-1,3-galactosidase
| ''Pseudoalteromonas distincta''
| Gal-α1,3-Gal
| '''Asp344'''
| Asp321 Asp345
| <cite>McGuire2020</cite>
|-
| [[GH113]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00004cd8 pdb_00004cd8]
| β-mannanase
| ''Alicyclobacillus acidocaldarius''
| mannobioimidazole
| '''Glu151'''
| Glu231
| <cite>Williams2014</cite>
|-
| [[GH116]]
| O
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''perpendicular''''' (anomaly)
| [{{PDBlink}}pdb_00008i5u pdb_00008i5u]
| β-glucosidase
| ''Thermoanaerobacterium xylanolyticum'' LX-11
| laminaribiose
| '''Asp593'''
| Glu441
| <cite>Pengthaisong2023</cite>
|-
| [[GH117]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00004ak7 pdb_00004ak7]
| α-1,3-3,6-anhydro-{{Smallcaps|l}}-galactosidase
| ''Bacteroides plebeius''
| neoagarobiose
| '''His302''' (relay from Asp320)
| Asp90
| <cite>Hehemann_2_2012</cite>
|-
| [[GH119]]
| T
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at GH57''
|
|
|
|
|
|
|-
| [[GH120]]
| none
| parallel β-helix and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00003vsv pdb_00003vsv]
| β-xylosidase XylC
| ''Thermoanaerobacterium saccharolyticum'' JW/SL-YS485
| {{Smallcaps|d}}-xylose
| '''Glu405'''
| Asp382
| <cite>Huang2012</cite>
|-
| [[GH123]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00005fr0 pdb_00005fr0]
| exo-β-N-acetyl-galactosaminidase
| ''Clostridium perfringens''
| ''N''-difluoroacetyl-{{Smallcaps|d}}-galactosamine
| '''Glu345'''
| internal
| <cite>Noach2016</cite>
|-
| [[GH124]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00006g1i pdb_00006g1i]
| endo-β-1,4-glucanase
| ''Acetivibrio thermocellus'' ATCC 27405
| fructosylated cellopentaose
| '''Glu203'''
| unknown
| <cite>Urresti2018</cite>
|-
| [[GH125]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00005m7y pdb_00005m7y]
| exo-α-1,6-mannosidase
| ''Clostridium perfringens''
| 1,6-α-mannotriose
| '''Asp220'''
| Glu393
| <cite>Alonso-Gil2016</cite>
|-
| [[GH127]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00003wrg pdb_00003wrg]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bifidobacterium longum''
| {{Smallcaps|l}}-arabinose
| '''Glu322'''
| Cys417
| <cite>Huang2014</cite>
|-
| [[GH128]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00006ufl pdb_00006ufl]
| β-1,3-glucanase
| ''Amycolatopsis mediterranei''
| laminarihexaose
| '''Glu102'''
| Glu199
| <cite>Santos2020</cite>
|-
| [[GH129]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00005wzn pdb_00005wzn]
| exo-α-''N''-acetylgalactosaminidase (NagBb)
| ''Bifidobacterium bifidum'' JCM 1254
| GalNAc
| '''Glu478'''
| Asp435
| <cite>Sato2017</cite>
|-
| [[GH130]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00005b0s pdb_00005b0s]
| β-1,2-mannobiose phosphorylase
| ''Listeria innocua''
| β-1,2-mannotriose
| '''Asp141''' relay
| phosphate
| <cite>Tsuda2015</cite>
|-
| [[GH133]]
| none
| (α/α)6
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00005d0f pdb_00005d0f]
| glycogen-debranching enzyme
| ''Nakaseomyces glabratus'' CBS 138
| maltopentaose
| '''Glu564'''
| Asp535
| <cite>Zhai2016</cite>
|-
| [[GH134]]
| none
| β + α
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00005jug pdb_00005jug]
| β-mannanase
| ''Streptomyces sp.''
| mannopentaose
| '''Glu45'''
| Asp57
| <cite>Jin2016</cite>
|-
| [[GH135]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00005d6t pdb_00005d6t]
| α-1,4-galactosaminogalactan
| ''Aspergillus clavatus''
| β-{{Smallcaps|d}}-GalpNAc
| '''Glu222'''
| Asp166
| <cite>Bamford2015</cite>

|-

| [[GH136]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00005gqf pdb_00005gqf]
| lacto-N-biosidase
| ''Bifidobacterium longum''
| lacto-N-biose
| '''Asp411'''
| Asp418
| <cite>Yamada2017</cite>
|-
| [[GH137]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|l}}
| unknown
| '''''anti'''''
| [{{PDBlink}}pdb_00005mui pdb_00005mui]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0996
| ''Bacteroides thetaiotaomicron''
| pectin oligosaccharide
| '''Glu240'''
| Glu159
| <cite>Ndeh2017</cite>
|-
| [[GH138]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00006hzg pdb_00006hzg]
| α-1,2-{{Smallcaps|d}}-galacturonidase
| ''Bacteroides paurosaccharolyticus''
| alpha-{{Smallcaps|d}}-galactopyranuronic
| '''Glu294'''
| Glu361
| <cite>Labourel2019</cite>
|-
| [[GH140]]
| A
| (β/α)6
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH144]]
| S
| (α/α)8
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00008xul pdb_00008xul]
| beta-1,2-glucanase
| ''Xanthomonas campestris''
| beta-1,2-glucoheptasaccharide
| '''Glu239'''
| unknown
| <cite>Nakajima2024</cite>
|-
| [[GH146]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00005opj pdb_00005opj]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bacteroides thetaiotaomicron''
| {{Smallcaps|l}}-arabinose
| '''Glu320'''
| Cys416
| <cite>Luis2018</cite>
|-
| [[GH147]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH148]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH149]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH156]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00006s0e pdb_00006s0e]
| exo-α-sialidase
| uncultured bacterium pG7
| N-acetyl-2,3-dehydro-2-deoxyneuraminic acid
| '''His134''' (relay from Asp132)
| Asp14
| <cite>Bule2019</cite>
|-
| [[GH157]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH158]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH161]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH162]]
| S
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00006imw pdb_00006imw]
| endo-β-1,2-glucanase
| ''Talaromyces funiculosus''
| beta-1,2-glucan
| '''Glu262''' via C3-OH of glc at subs. +2
| Asp446
| <cite>Tanaka2019</cite>
|-
| [[GH164]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00006t75 pdb_00006t75]
| β-mannosidase
| ''Bacteroides salyersiae''
| 2-deoxy-2-F-mannosyl
| '''Glu160'''
| Glu297
| <cite>Armstrong2020</cite>
|-
| [[GH167]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|

|

|
|-
| [[GH168]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00008ya7 pdb_00008ya7]
| endo-α-1,3-{{Smallcaps|l}}-fucanase (Fun168A)
| ''Wenyingzhuangia fucanilytica'' CZ1127
| sulfated fucotetraose
| '''Glu264'''
| Asp206
| <cite>Chen2024</cite>
|-
| [[GH169]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH172]]
| none
| β-jelly roll
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00007v1w pdb_00007v1w]
| difructose-anhydride synthase
| ''Bifidobacterium dentum''
| beta-{{Smallcaps|d}}-arabinofuranose
| '''Glu270'''
| Glu291
| <cite>Kashima2021</cite>
|-
| [[GH173]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH178]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at e.g. GH15''
|
|
|
|
|
|
|-
| [[GH181]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00008axi pdb_00008axi]
| exo-α-sialidase
| ''Akkermansia muciniphila''
| 2-deoxy-2,3-dehydro-''N''-acetyl-neuraminic acid + T-antigen disaccharide
| '''Asp345'''
| Glu218
| <cite>Shuoker2023</cite>
|-
| [[GH183]]
| none
| 5-bladed β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00008ic1 pdb_00008ic1]
| endo-α-1,5-{{Smallcaps|d}}-arabinofuranosidase
| ''Microbacterium arabinogalactanolyticum'' JCM 9171
| α-{{Smallcaps|d}}-Araf-(1,5)-α-{{Smallcaps|d}}-Araf-(1,5)-α-{{Smallcaps|d}}-Araf-(1,5)-α-{{Smallcaps|d}}-Araf
| '''Asp51'''
| Asp33
| <cite>Shimokawa2023</cite>
|-
| [[GH186]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00008ip1 pdb_00008ip1]
| β-1,2-glucanase
| ''Escherechia coli''
| β-1,2-glucan
| '''Asp388'''
| Asp300 + 3 waters
| <cite>Motouchi2023</cite>
|-
| [[GH192]]
| S
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at e.g. GH144''
|
|
|
|
|
|
|-
| [[GH193]]
| S
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at e.g. GH144''
|
|
|
|
|
|
|-
| [[GH194]]
| S
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at e.g. GH144''
|
|
|
|
|
|
|-
| [http://www.cazy.org/GH0.html n.c.*]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00002vjj pdb_00002vjj]
| endo-α-N-acetylglucosaminidase
| Bacteriophage HK620
| O18A1 O-antigen hexasaccharide
| '''Asp339'''
| Glu372
| <cite>Barbirz2008</cite>
|}
<nowiki>*</nowiki> n.c.: Found among the collection of [http://www.cazy.org/GH0.html non-classified GH sequences in the CAZy Database].

== References ==

<biblio>
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# Dennis2006 pmid=16565725
# Abbott2009 pmid=19181667
# Hehemann_1_2012 pmid=23150581
# Ficko-Blean2008 pmid=18443291
# Zhu2009 pmid=20081828
# Sogabe2011 pmid=21543843
# Nam2015 pmid=26041776
# Nagae2007 pmid=17459873
# Kitamura2008 pmid=18981178
# Higgins2009 pmid=19608744
# van_Straaten2007 pmid=17502382
# van_Asselt2000 pmid=10684641
# Ndeh2017 pmid=28329766
# Labourel2019 pmid=30877196
# Nakajima2024 Nakajima M. et al. ''Extensive distribution of β-1,2-glucanases: finding of new glycoside hydrolase families of β-1,2-glucanases.'' BioRxiv preprint 2024. https://doi.org/10.1101/2024.02.06.578578
# Luis2018 pmid=29255254
# Bule2019 pmid=31645552
# Jin2016 Jin Y, Petricevic M, John A, Raich L, Jenkins H, Portela De Souza L, Cuskin F, Gilbert HJ, Rovira C, Goddard-Borger ED, Williams SJ, and Davies GJ. ''A β-Mannanase with a Lysozyme-like Fold and a Novel Molecular Catalytic Mechanism.'' ACS Cent Sci. 2016 Nov [http://dx.doi.org/10.1021/acscentsci.6b00232 DOI:10.1021/acscentsci.6b00232]
# Yamada2017 pmid=28392148

# Bamford2015 pmid=26342082

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</biblio>
[[Category:Definitions and explanations]]

Syn/anti lateral protonation

2026-04-15T12:14:50Z

Wim Nerinckx: GH192-3-4 predicted syn by clan

{{CuratorApproved}}
* [[Author]]: [[User:Wim Nerinckx|Wim Nerinckx]]
* [[Responsible Curator]]: [[User:Spencer Williams|Spencer Williams]]

----

== Overview ==

This page provides a table that summarizes the spatial positioning of the catalytic [[general acid]] residue in the active sites of [[glycoside hydrolase]]s, relative to the substrate. The table below updates those found in the seminal paper on this concept by Heightman and Vasella <cite>HeightmanVasella1999</cite>, and a following paper by Nerinckx ''et al.'' <cite>Nerinckx2005</cite>.

== Background ==

The ''"not from above, but from the side"'' concept of semi-lateral glycosidic oxygen [[General_acid/base|protonation]] by [[glycoside hydrolase]]s was introduced by Heightman and Vasella <cite>HeightmanVasella1999</cite>. It was originally only described for [[Anomeric centre (alpha and beta)|beta]]-equatorial [[glycoside hydrolase]]s, but appears to be equally applicable to enzymes acting on an [[Anomeric centre (alpha and beta)|alpha]]-axial glycosidic bond <cite>Nerinckx2005</cite>. When dividing [[Sub-site nomenclature|subsite -1]] into half-spaces by a plane defined by the glycosidic oxygen and C1' and H1' of the –1 glycoside, many ligand-complexed structures reveal that the [[General_acid/base|proton donor]] is positioned either in the ''syn'' half-space (near the ring-oxygen of the –1 glycoside), or in the ''anti'' half-space (on the opposite side of the ring-oxygen). Members of the same GH [[Families|family]] appear to share a common ''syn'' or ''anti'' [[General_acid/base|protonator]] arrangement and further, this specificity appears to be preserved within [[Clans|Clans]] of [[Families|families]]. This page's compilation of [[Sub-site nomenclature|subsite -1]] occupied complexes shows that about 70% of all GH [[Families|families]] are ''anti'' [[General_acid/base|protonators]].

Closer inspection of crystal structures of [[Sub-site nomenclature|–1/+1 subsite]]-spanning substrates, or substrate-analogue ligands, in complex with enzymes reveals a further intriguing corollary <cite>Nerinckx2005 Wu2012</cite>. In substrate-bound complexes with ''anti'' [[General_acid/base|protonating]] GH enzymes, the scissile [[Anomeric centre (alpha and beta)|anomeric bond]] (often studied using the thio-analogue) shows a dihedral angle φ (O5'-C1'-[O,S]x-Cx) that is in the lowest-energy synclinal (gauche) conformation. The rationale for this is that a minus synclinal dihedral angle φ for an equatorial glycosidic bond, or plus synclinal for an axial glycosidic bond <cite>Perez1978</cite>, allows for hyperconjugative overlap of the C1'-O5' antibonding orbital with an antiperiplanar-oriented lone pair orbital lobe of the glycosidic oxygen, thereby creating partial double bond character and stabilization of the glycosidic bond by 4–5 kcal/mol; this ground-state stabilizing phenomenon is known as the ‘exo-anomeric effect’ <cite>Cramer1997 Johnson2009 Alonso2016</cite>. ''Anti'' [[General_acid/base|protonation]] occurs on the glycosidic oxygen’s antiperiplanar lone pair, thereby removing the stabilizing exo-anomeric effect. This suggests that ''anti'' [[General_acid/base|protonation]] is an enzymic approach for lowering the activation barrier leading to the [[Transition state|transition state]] (Figure 1 centre).

''Syn'' [[General_acid/base|protonating]] [[glycoside hydrolase]]s apparently make use of a different approach <cite>Nerinckx2005 Wu2012</cite>. In many [[Sub-site nomenclature|–1/+1 subsite]]-spanning ligand complexes, the dihedral angle φ of the scissile anomeric bond has been rotated away from its lowest-energy synclinal position: clockwise to minus-anticlinal or antiperiplanar for beta-equatorial; counterclockwise to plus-anticlinal or antiperiplanar for alpha-axial [[Anomeric centre (alpha and beta)|anomeric bonds]]. This removes the hyperconjugative overlap and thus also the stabilizing exo-anomeric effect. And because of this rotation, a lone pair of the glycosidic oxygen is directed into the ''syn'' half-space, allowing it to be protonated by the ''syn''-positioned [[General_acid/base|proton donor]] (Figure 1 right).

[[File:Syn_anti.jpg|800px|thumb|center|Figure 1. Newman projections, with the glycosidic oxygen as proximal atom and the anomeric carbon as distal atom, showing ''anti'' (centre) versus ''syn'' (right) semi-lateral [[General_acid/base|protonation]] in beta-equatorial (top) and alpha-axial (bottom) [[glycoside hydrolase]]s. The indicated φ is the dihedral angle for O5'-C1'-O4-C4.]]

== Table of ''syn/anti'' protonation examples ==

This table contains only one example per GH [[Families|family]] of a ligand-complexed protein structure where the ''syn'' or ''anti'' positioning of the [[General_acid/base|proton donor]] can be clearly observed; other examples may be available on a [[Families|family-by-family]] basis. The reader is thus advised to consult the [http://www.cazy.org/fam/acc_GH.html#table CAZy database] for a current, comprehensive list of CAZyme structures. Where available, the selected examples are Michaelis-type complexes with the ligand spanning the [[Sub-site nomenclature|-1/+1 subsites]], since these have an intact glycosidic or thioglycosidic bond, or are ''N''-analogs of the substrate (''e.g.'' acarbose). In some examples, the [[General_acid/base|proton donor]] has been mutated (''e.g.'', to the corresponding amide or to an alanine), and in those cases one may wish to look at a superposition of the given PDB example with the structure of the native enzyme. If a Michaelis-type complex is not yet available, the second and third example choices, respectively, are trapped glycosyl-enzyme [[intermediate]]s and product complexes where [[Sub-site nomenclature|subsite -1]] is occupied.

''Please also be aware that this is a large table with many data. Please contact the page Author or Responsible Curator with corrections.''

=== Table ===
This table can be re-sorted by clicking on the icons in the header (''javascript must be turned on in your browser''). To reset the page to be sorted by GH family, click the ''View'' tab at the very top of the page.

{| {{Prettytable}} class="sortable"
|- valign="top"
! '''Family'''
! '''Clan'''
! '''Structure fold '''
! '''Anomeric specificity'''
! '''Mechanism'''
! '''''Syn/anti'' protonator'''
! '''Example PDB ID'''
! '''Enzyme'''
! '''Organism'''
! '''Ligand'''
! '''General acid'''
! '''Nucleophile or General base'''
! '''Reference'''
|-
| [[GH1]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002cer pdb_00002cer]
| β-glycosidase S
| ''Sulfolobus solfataricus'' P2
| phenethyl glucoimidazole
| '''Glu206'''
| Glu387
| <cite>Gloster2006</cite>
|-
| [[GH2]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002vzu pdb_00002vzu]
| exo-β-glucosaminidase
| ''Amicolatopsis orientalis''
| PNP-β-{{Smallcaps|d}}-glucosamine
| '''Glu469'''
| Glu541
| <cite>van_Bueren2009</cite>
|-
| [[GH3]]
| none
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001iex pdb_00001iex]
| exo-1,3-1,4-glucanase
| ''Hordeum vulgare''
| thiocellobiose
| '''Glu491'''
| Asp285
| <cite>Hrmova2001</cite>
|-
| [[GH4]]
| none
| Rossmann + α6/β3 + β3/α4
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001u8x pdb_00001u8x]
| 6-P-α-glucosidase
| ''Bacillus subtilis''
| alpha-{{Smallcaps|d}}-glucose-6-phosphate
| '''Asp172'''
| not applicable
| <cite>Rajan2004</cite>
|-
| [[GH5]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001h2j pdb_00001h2j]
| endo-β-1,4-glucanase
| ''Bacillus agaradhaerens''
| 2',4'-DNP-2-F-cellobioside
| '''Glu129'''
| Glu228
| <cite>Varrot2003</cite>
|-
| [[GH6]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00001qjw pdb_00001qjw]
| cellobiohydrolase 2
| ''Hypocrea jecorina''
| (Glc)2-S-(Glc)2
| '''Asp221'''
| debated
| <cite>Zhou1999</cite>
|-
| [[GH7]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00001ovw pdb_00001ovw]
| endo-1,4-glucanase
| ''Fusarium oxysporum''
| thio-(Glc)5
| '''Glu202'''
| Glu197
| <cite>Sulzenbacher1999</cite>
|-
| [[GH8]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00001kwf pdb_00001kwf]
| endo-1,4-glucanase
| ''Clostridium thermocellum''
| cellopentaose
| '''Glu95'''
| Asp278
| <cite>Guerin2002</cite>
|-
| [[GH9]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00001rq5 pdb_00001rq5]
| cellobiohydrolase
| ''Clostridium thermocellum''
| cellotetraose
| '''Glu795'''
| Asp383
| <cite>Schubot2004</cite>
|-
| [[GH10]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002d24 pdb_00002d24]
| β-1,4-xylanase
| ''Streptomyces olivaceoviridis'' E-86
| xylopentaose
| '''Glu128'''
| Glu236
| <cite>Suzuki2009</cite>
|-
| [[GH11]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00004hk8 pdb_00004hk8]
| endo-β-1,4-xylanase
| ''Hypocrea jecorina''
| xylohexaose
| '''Glu177'''
| Glu86
| <cite>Wan2014</cite>
|-
| [[GH12]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00001w2u pdb_00001w2u]
| endoglucanase
| ''Humicola grisea''
| thiocellotetraose
| '''Glu205'''
| Glu120
| <cite>Sandgren2004</cite>
|-
| [[GH13]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001cxk pdb_00001cxk]
| β-cyclodextrin glucanotransferase
| ''Bacillus circulans''
| maltononaose
| '''Glu257'''
| Asp229
| <cite>Uitdehaag1999</cite>
|-
| [[GH14]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00001itc pdb_00001itc]
| β-amylase
| ''Bacillus cereus''
| maltopentaose
| '''Glu172'''
| Glu367
| <cite>Miyake2003</cite>
|-
| [[GH15]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00001dog pdb_00001dog]
| glucoamylase
| ''Aspergillus awamori''
| 1-deoxynojirimycin
| '''Glu179'''
| Glu400
| <cite>Harris1993</cite>
|-
| [[GH16]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00001urx pdb_00001urx]
| β-agarase A
| ''Zobellia galactanivorans''
| oligoagarose
| '''Glu152'''
| Glu147
| <cite>Allouch2004</cite>
|-
| [[GH17]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00004gzj pdb_00004gzj]
| endo-β-1,3-glucanase
| ''Solanum tuberosum''
| laminaratriose + laminarabiose
| '''Glu118'''
| Glu259
| <cite>Wojtkowiak2013</cite>
|-
| [[GH18]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001ffr pdb_00001ffr]
| chitinase A
| ''Serratia marcescens''
| (NAG)6
| '''Glu315'''
| internal
| <cite>Papanikolau2001</cite>
|-
| [[GH19]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00003wh1 pdb_00003wh1]
| chitinase
| ''Bryum coronatum''
| (GlcNAc)4
| '''Glu61'''
| Glu70
| <cite>Ohnuma2014</cite>
|-
| [[GH20]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001c7s pdb_00001c7s]
| chitobiase
| ''Serratia marcescens''
| chitobiose
| '''Glu540'''
| internal
| <cite>Prag2000</cite>
|-
| [[GH22]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00001h6m pdb_00001h6m]
| lysozyme C
| ''Gallus gallus''
| Chit-2-F-chitosyl
| '''Glu35'''
| Asp52
| <cite>Vocadlo2001</cite>
|-
| [[GH23]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00001lsp pdb_00001lsp]
| lysozyme G
| ''Cygnus atratus''
| Bulgecin A
| '''Glu73'''
| internal
| <cite>Karlsen1996</cite>
|-
| [[GH24]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_0000148l pdb_0000148l]
| lysozyme E
| Bacteriophage T4
| chitobiosyl
| '''Glu11'''
| Glu26
| <cite>Baldwin1993</cite>
|-
| [[GH26]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002vx6 pdb_00002vx6]
| exo-β-mannanase
| ''Cellvibrio japonicus'' Ueda107
| Gal1Man4
| '''Glu221'''
| Glu338
| <cite>Cartmell2008</cite>
|-
| [[GH27]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}} / beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00003lrm pdb_00003lrm]
| α-galactosidase
| ''Saccharomyces cerevisiae''
| raffinose
| '''Asp209'''
| Asp141
| <cite>Fernandez-Leiro2010</cite>
|-
| [[GH28]]
| N
| β-helix
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00002uvf pdb_00002uvf]
| exo-polygalacturonosidase
| ''Yersinia enterocolitica'' ATCC9610D
| digalacturonic acid
| '''Asp402'''
| Asp381 Asp403
| <cite>Abbott2007</cite>
|-
| [[GH29]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00003uet pdb_00003uet]
| α-1,3/4-fucosidase
| ''Bifidobacterium longum'' subsp. infantis
| lacto-''N''-fucopentaose II
| '''Glu217'''
| Asp172
| <cite>Sakurama2012</cite>
|-
| [[GH30]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002y24 pdb_00002y24]
| glucurono-xylanase
| ''Dickea chrysanthemi'' D1
| glucuronoxylan tetrasaccharide
| '''Glu165'''
| Glu253
| <cite>Urbanikova2011</cite>
|-
| [[GH31]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002qmj pdb_00002qmj]
| maltase-glucoamylase
| ''Homo sapiens''
| acarbose
| '''Asp542'''
| Asp443
| <cite>Sim2008</cite>
|-
| [[GH32]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002add pdb_00002add]
| fructan β-(2,1)-fructosidase
| ''Cichorium intybus''
| sucrose
| '''Glu201'''
| Asp22
| <cite>Verhaest2007</cite>
|-
| [[GH33]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001s0i pdb_00001s0i]
| transsialidase
| ''Trypanosoma cruzi''
| sialyllactose
| '''Asp59'''
| Tyr342 (with Glu230)
| <cite>Amaya2004</cite>
|-
| [[GH34]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00004gzw pdb_00004gzw]
| N2 neuraminidase
| ''Influenza'' A Tanzania/205/2010 H3N2
| α-{{Smallcaps|d}}-Neup5Ac-(2,3)-β-{{Smallcaps|d}}-Galp-(1,4)-β-{{Smallcaps|d}}-GlcpNAc
| '''Asp151'''
| Tyr406 (with Glu277)
| <cite>Zhu2012</cite>
|-
| [[GH35]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00003ogv pdb_00003ogv]
| β-galactosidase
| ''Hypocrea jecorina''
| 2-phenylethyl 1-thio-β-{{Smallcaps|d}}-galactopyranoside
| '''Glu200'''
| Glu298
| <cite>Maksimainen2011</cite>
|-
| [[GH36]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00004fnu pdb_00004fnu]
| β-galactosidase
| ''Geobacillus stearothermophilus''
| stachyose
| '''Asp584'''
| Asp478
| <cite>Merceron2012</cite>
|-
| [[GH37]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00002jf4 pdb_00002jf4]
| trehalase
| ''Escherichia coli''
| validoxylamine
| '''Asp312'''
| Glu496
| <cite>Gibson2007</cite>
|-
| [[GH38]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00003czn pdb_00003czn]
| Golgi α-mannosidase II
| ''Drosophila melanogaster''
| GlcNAcMan(5)GlcNAc(2)
| '''Asp341'''
| Asp204
| <cite>Shah2008</cite>
|-
| [[GH39]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002bfg pdb_00002bfg]
| β-xylosidase
| ''Geobacillus stearothermophilus''
| 2,5-dinitrophenyl-β-{{Smallcaps|d}}-xyloside
| '''Glu160'''
| Glu278
| <cite>Czjzek2005</cite>
|-
| [[GH42]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00004ucf pdb_00004ucf]
| β-galactosidase
| ''Bifidobacterium bifidum''
| {{Smallcaps|d}}-galactose
| '''Glu161'''
| Glu320
| <cite>Godoy2016</cite>
|-
| [[GH43]]
| F
| 5-fold β-propeller
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00003akh pdb_00003akh]
| exo-1,5-α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces avermitilis''
| α-1,5-arabinofuranotriose
| '''Glu196'''
| Asp220
| <cite>Fujimoto2010</cite>
|-
| [[GH44]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002eqd pdb_00002eqd]
| endoglucanase
| ''Clostridium thermocellum''
| cellooctaose
| '''Glu186'''
| Glu359
| <cite>Kitago2007</cite>
|-
| [[GH45]]
| none
| 6-stranded β-barrel
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00004eng pdb_00004eng]
| endo-1,4-glucanase
| ''Humicola insolens''
| cellohexaose
| '''Asp121'''
| Asp10
| <cite>Davies1996</cite>
|-
| [[GH46]]
| I
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00004olt pdb_00004olt]
| chitosanase
| ''Microbacterium sp.'' OU01
| hexa-glucosamine
| '''Glu25'''
| Asp43
| <cite>Lyu2014</cite>
|-
| [[GH47]]
| none
| (α/α)7
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00001x9d pdb_00001x9d]
| α-mannosidase I
| ''Homo sapiens''
| Me-2-S-(α-Man)-2-thio-α-Man
| '''Asp463'''
| Glu599
| <cite>Karaveg2005</cite>, <cite>Nerinckx2008</cite>
|-
| [[GH48]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH8''
|
|
|
|
|
|
|-
| [[GH49]]
| N
| β-helix
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH28''
|
|
|
|
|
|
|-
| [[GH50]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00004bq5 pdb_00004bq5]
| exo-β-agarase
| ''Saccharophagus degradans''
| neoagarotetraose
| '''Glu535'''
| Glu695
| <cite>Pluvinage2013</cite>
|-
| [[GH51]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001qw9 pdb_00001qw9]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Geobacillus stearothermophilus''
| PNP-{{Smallcaps|l}}-arabinofuranoside
| '''Glu175'''
| Glu294
| <cite>Hoevel2003</cite>
|-
| [[GH52]]
| O
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| '' predicted perpendicular by clan, see at GH116''
| [{{PDBlink}}pdb_00004c1p pdb_00004c1p]
| β-xylosidase
| ''Geobacillus thermoglucosidasius''
| xylobiose
| '''Asp517'''
| Glu537
| <cite>Espina2014</cite>
|-
| [[GH53]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002ccr pdb_00002ccr]
| β-1,4-galactanase
| ''Bacillus licheniformis''
| galactotriose
| '''Glu165'''
| Glu263
| <cite>Le_Nours2009</cite>
|-
| [[GH54]]
| none
| β-sandwich
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001wd4 pdb_00001wd4]
| α-{{Smallcaps|l}}-arabinofuranosidase B
| ''Aspergillus kawachii''
| {{Smallcaps|l}}-arabinofuranose
| '''Asp297'''
| Glu221
| <cite>Miyanaga2004</cite>
|-
| [[GH55]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00004tz5 pdb_00004tz5]
| exo-β-1,3-glucanase
| ''Streptomyces sp.'' SirexAA-E
| laminarihexaose
| '''Glu502'''
| unknown
| <cite>Bianchetti2015</cite>
|-
| [[GH56]]
| none
| (β/α)7
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001fcv pdb_00001fcv]
| hyaluronidase
| ''Apis mellifera''
| (hyaluron.)4
| '''Glu113'''
| internal
| <cite>Markovic-Housley2000</cite>
|-
| [[GH57]]
| T
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001k1y pdb_00001k1y]
| glucanotransferase
| ''Thermococcus litoralis''
| acarbose
| '''Asp214'''
| Glu123
| <cite>Imamura2003</cite>
|-
| [[GH59]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00004ccc pdb_00004ccc]
| β-galactocerebrosidase
| ''Mus musculus''
| PNP-β-{{Smallcaps|d}}-galactoside
| '''Glu182'''
| Glu258
| <cite>Hill2013</cite>
|-
| [[GH62]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00003wn0 pdb_00003wn0]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces coelicolor''
| β-{{Smallcaps|l}}-Arabinofuranose
| '''Glu361'''
| Asp202
| <cite>Maehara2014</cite>
|-
| [[GH63]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00005ca3 pdb_00005ca3]
| α-glucosidase
| ''Escherichia coli''
| glucose and lactose
| '''Asp501'''
| Glu727
| <cite>Miyazaki2016</cite>
|-
| [[GH65]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00004ktr pdb_00004ktr]
| 2-O-α-glucosylglycerol phosphorylase
| ''Bacillus selenitireducens''
| isofagomine
| '''Glu475'''
| phosphate
| <cite>Touhara2014</cite>
|-
| [[GH66]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00005axh pdb_00005axh]
| dextranase
| ''Thermoanaerobacter pseudethanolicus''
| isomaltohexaose
| '''Glu374'''
| Asp312
| <cite>Suzuki2016</cite>
|-
| [[GH67]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00001l8n pdb_00001l8n]
| α-glucuronidase
| ''Geobacillus stearothermophilus''
| 4-O-methyl-{{Smallcaps|d}}-glucuronic acid and xylotriose
| '''Glu286'''
| Asp364 Glu392
| <cite>Golan2004</cite>
|-
| [[GH68]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001pt2 pdb_00001pt2]
| levansucrase
| ''Bacillus subtilis''
| sucrose
| '''Glu342'''
| Asp86
| <cite>Meng2003</cite>
|-
| [[GH70]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00003aic pdb_00003aic]
| glucansucrase
| ''Streptococcus mutans''
| α-acarbose
| '''Glu515'''
| Asp477
| <cite>Ito2011</cite>
|-
| [[GH72]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002w62 pdb_00002w62]
| β-1,3-glucanotransferase
| ''Saccharomyces cerevisiae'' S288C
| laminaripentaose
| '''Glu176'''
| Glu275
| <cite>Hurtado-Gerrero2009</cite>
|-
| [[GH73]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| unknown
| '''''syn'''''
| [{{PDBlink}}pdb_00007pod pdb_00007pod]
| peptidoglycan endo-β-1,4-''N''-acetylglucosaminidase
| ''Streptococcus pneumoniae'' R6
| NAG-NAM-NAG-NAM tetrasaccharide
| '''Glu585'''
| unknown
| <cite>Martinez-Caballero2023</cite>
|-
| [[GH74]]
| none
| 7-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00002ebs pdb_00002ebs]
| cellobiohydrolase (OXG-RCBH)
| ''Geotrichum sp.'' m128
| xyloglucan heptasaccharide
| '''Asp465'''
| Asp35
| <cite>Yaoi2007</cite>
|-
| [[GH76]]
| none
| (α/α)6
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00005agd pdb_00005agd]
| endo-α-1,6-mannanase
| ''Bacillus circulans''
| α-1,6-mannopentaose
| '''Asp125'''
| Asp124
| <cite>Thompson2015</cite>
|-
| [[GH77]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002oww pdb_00002oww]
| 4-α-glucanotransferase
| ''Thermus thermofilus''
| acarbose + 4-deoxy-α-{{Smallcaps|d}}-glucose
| '''Glu340'''
| Asp293
| <cite>Barends2007</cite>
|-
| [[GH78]]
| H
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00003w5n pdb_00003w5n]
| α-{{Smallcaps|l}}-rhamnosidase
| ''Streptomyces avermitilis''
| {{Smallcaps|l}}-rhamnose
| '''Glu636'''
| Glu895
| <cite>Fujimoto2013</cite>
|-
| [[GH79]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00005e9c pdb_00005e9c]
| heparanase
| ''Homo sapiens''
| heparin tetrasaccharide
| '''Glu225'''
| Glu343
| <cite>Wu2015</cite>
|-
| [[GH80]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH24''
|
|
|
|
|
|
|-
| [[GH81]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00005t4g pdb_00005t4g]
| endo-β-1,3-glucanase
| ''Bacillus halodurans'' C-125
| laminarin
| '''Asp466'''
| Glu542
| <cite>Pluvinage2017</cite>
|-
| [[GH83]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001z4x pdb_00001z4x]
| hemagglutinin-neuraminidase
| Simian virus 5
| α-2,3-sialyllactose
| '''Asp187''' on flexible loop
| Tyr523 (with Glu390)
| <cite>Yuan2005</cite>
|-
| [[GH84]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002chn pdb_00002chn]
| β-''N''-acetyl-glucosaminidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| NAG-thiazoline
| '''Glu242'''
| internal
| <cite>Dennis2006</cite>
|-
| [[GH85]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002w92 pdb_00002w92]
| endo-β-''N''-acetyl-glucosaminidase D
| ''Streptococcus pneumoniae'' TIGR4
| NAG-thiazoline
| '''Glu337'''
| internal
| <cite>Abbott2009</cite>
|-
| [[GH86]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00004aw7 pdb_00004aw7]
| β-porphyranase
| ''Bacteroides plebeius''
| porphyran fragment
| '''Glu152'''
| Glu279
| <cite>Hehemann_1_2012</cite>
|-
| [[GH89]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002vcb pdb_00002vcb]
| α-''N''-acetyl-glucosaminidase
| ''Clostridium perfringens''
| PUGNAc
| '''Glu483'''
| Glu601
| <cite>Ficko-Blean2008</cite>
|-
| [[GH92]]
| none
| (α/α)6 and β-sandwich
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00002ww1 pdb_00002ww1]
| α-1,2-mannosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| thiomannobioside
| '''Glu533'''
| Asp644 Asp642
| <cite>Zhu2009</cite>
|-
| [[GH93]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00003a72 pdb_00003a72]
| exo-arabinanase
| ''Penicillium chrysogenum''
| arabinobiose
| '''Glu246'''
| Glu174
| <cite>Sogabe2011</cite>
|-
| [[GH94]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00004zli pdb_00004zli]
| cellobionic acid phosphorylase
| ''Saccharophagus degradans''
| 3-O-β-{{Smallcaps|d}}-glucopyranosyl-α-{{Smallcaps|d}}-glucopyranuronic acid
| '''Asp472'''
| phosphate
| <cite>Nam2015</cite>
|-
| [[GH95]]
| none
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00002ead pdb_00002ead]
| α-1,2-{{Smallcaps|l}}-fucosidase
| ''Bifidobacterium bifidum''
| Fuc-α-1,2-Gal
| '''Glu566'''
| Asn423 Asp766
| <cite>Nagae2007</cite>
|-
| [[GH97]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining + inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00002zq0 pdb_00002zq0]
| α-glucosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| acarbose
| '''Glu532'''
| Glu508
| <cite>Kitamura2008</cite>
|-
| [[GH98]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00002wmg pdb_00002wmg]
| endo-β-1,4-galactosidase
| ''Streptococcus pneumoniae''
| A-LewisY pentasaccharide
| '''Glu158'''
| Asp251 Glu301
| <cite>Higgins2009</cite>
|-
| [[GH99]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00004ad4 pdb_00004ad4]
| endo-α-mannosidase
| ''Bacteroides xylanisolvens''
| glucose-1,3-isofagomine and α-1,2- mannobiose
| '''Glu336'''
| debated
| <cite>Thompson2012</cite>
|-
| [[GH100]]
| G
| (α/α)6 core
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00005gop pdb_00005gop]
| invertase
| ''Anabaena (Nostoc) sp.'' pcc7120
| sucrose
| '''Asp188'''
| Glu414
| <cite>Xie2016</cite>
|-
| [[GH101]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00005a56 pdb_00005a56]
| endo-α-N-acetylgalactosaminidase
| ''Streptococcus pneumoniae'' TIGR4
| β-{{Smallcaps|d}}-Galp-(1-3)-α-{{Smallcaps|d}}-GalpNAc-(1)-methyl
| '''Glu796''' +water
| Asp764
| <cite>Gregg2015</cite>
|-
| [[GH102]]
| none
| double-ψ β-barrel
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00002pi8 pdb_00002pi8]
| lytic transglycosylase A
| ''Escherichia coli''
| chitohexaose
| '''Asp308'''
| none
| <cite>van_Straaten2007</cite>
|-
| [[GH103]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00001d0k pdb_00001d0k]
| lytic transglycosylase SLT35
| ''Escherichia coli''
| murodipeptides
| '''Glu162'''
| internal
| <cite>van_Asselt2000</cite>
|-
| [[GH106]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00005mwk pdb_00005mwk]
| α-{{Smallcaps|l}}-rhamnosidase BT_0986
| ''Bacteroides thetaiotaomicron''
| pectin heptasaccharide
| '''Glu461'''
| Glu593 or Glu561
| <cite>Ndeh2017</cite>
|-
| [[GH107]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| ''predicted syn by clan''
| ''see at GH29''
|
|
|
|
|
|
|-
| [[GH110]]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00007jwf pdb_00007jwf]
| α-1,3-galactosidase
| ''Pseudoalteromonas distincta''
| Gal-α1,3-Gal
| '''Asp344'''
| Asp321 Asp345
| <cite>McGuire2020</cite>
|-
| [[GH113]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00004cd8 pdb_00004cd8]
| β-mannanase
| ''Alicyclobacillus acidocaldarius''
| mannobioimidazole
| '''Glu151'''
| Glu231
| <cite>Williams2014</cite>
|-
| [[GH116]]
| O
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''perpendicular''''' (anomaly)
| [{{PDBlink}}pdb_00008i5u pdb_00008i5u]
| β-glucosidase
| ''Thermoanaerobacterium xylanolyticum'' LX-11
| laminaribiose
| '''Asp593'''
| Glu441
| <cite>Pengthaisong2023</cite>
|-
| [[GH117]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00004ak7 pdb_00004ak7]
| α-1,3-3,6-anhydro-{{Smallcaps|l}}-galactosidase
| ''Bacteroides plebeius''
| neoagarobiose
| '''His302''' (relay from Asp320)
| Asp90
| <cite>Hehemann_2_2012</cite>
|-
| [[GH119]]
| T
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at GH57''
|
|
|
|
|
|
|-
| [[GH120]]
| none
| parallel β-helix and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00003vsv pdb_00003vsv]
| β-xylosidase XylC
| ''Thermoanaerobacterium saccharolyticum'' JW/SL-YS485
| {{Smallcaps|d}}-xylose
| '''Glu405'''
| Asp382
| <cite>Huang2012</cite>
|-
| [[GH123]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00005fr0 pdb_00005fr0]
| exo-β-N-acetyl-galactosaminidase
| ''Clostridium perfringens''
| ''N''-difluoroacetyl-{{Smallcaps|d}}-galactosamine
| '''Glu345'''
| internal
| <cite>Noach2016</cite>
|-
| [[GH124]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00006g1i pdb_00006g1i]
| endo-β-1,4-glucanase
| ''Acetivibrio thermocellus'' ATCC 27405
| fructosylated cellopentaose
| '''Glu203'''
| unknown
| <cite>Urresti2018</cite>
|-
| [[GH125]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00005m7y pdb_00005m7y]
| exo-α-1,6-mannosidase
| ''Clostridium perfringens''
| 1,6-α-mannotriose
| '''Asp220'''
| Glu393
| <cite>Alonso-Gil2016</cite>
|-
| [[GH127]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00003wrg pdb_00003wrg]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bifidobacterium longum''
| {{Smallcaps|l}}-arabinose
| '''Glu322'''
| Cys417
| <cite>Huang2014</cite>
|-
| [[GH128]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00006ufl pdb_00006ufl]
| β-1,3-glucanase
| ''Amycolatopsis mediterranei''
| laminarihexaose
| '''Glu102'''
| Glu199
| <cite>Santos2020</cite>
|-
| [[GH129]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00005wzn pdb_00005wzn]
| exo-α-''N''-acetylgalactosaminidase (NagBb)
| ''Bifidobacterium bifidum'' JCM 1254
| GalNAc
| '''Glu478'''
| Asp435
| <cite>Sato2017</cite>
|-
| [[GH130]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00005b0s pdb_00005b0s]
| β-1,2-mannobiose phosphorylase
| ''Listeria innocua''
| β-1,2-mannotriose
| '''Asp141''' relay
| phosphate
| <cite>Tsuda2015</cite>
|-
| [[GH133]]
| none
| (α/α)6
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00005d0f pdb_00005d0f]
| glycogen-debranching enzyme
| ''Nakaseomyces glabratus'' CBS 138
| maltopentaose
| '''Glu564'''
| Asp535
| <cite>Zhai2016</cite>
|-
| [[GH134]]
| none
| β + α
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00005jug pdb_00005jug]
| β-mannanase
| ''Streptomyces sp.''
| mannopentaose
| '''Glu45'''
| Asp57
| <cite>Jin2016</cite>
|-
| [[GH136]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00005gqf pdb_00005gqf]
| lacto-N-biosidase
| ''Bifidobacterium longum''
| lacto-N-biose
| '''Asp411'''
| Asp418
| <cite>Yamada2017</cite>
|-
| [[GH137]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|l}}
| unknown
| '''''anti'''''
| [{{PDBlink}}pdb_00005mui pdb_00005mui]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0996
| ''Bacteroides thetaiotaomicron''
| pectin oligosaccharide
| '''Glu240'''
| Glu159
| <cite>Ndeh2017</cite>
|-
| [[GH138]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00006hzg pdb_00006hzg]
| α-1,2-{{Smallcaps|d}}-galacturonidase
| ''Bacteroides paurosaccharolyticus''
| alpha-{{Smallcaps|d}}-galactopyranuronic
| '''Glu294'''
| Glu361
| <cite>Labourel2019</cite>
|-
| [[GH140]]
| A
| (β/α)6
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH144]]
| S
| (α/α)8
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00008xul pdb_00008xul]
| beta-1,2-glucanase
| ''Xanthomonas campestris''
| beta-1,2-glucoheptasaccharide
| '''Glu239'''
| unknown
| <cite>Nakajima2024</cite>
|-
| [[GH146]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00005opj pdb_00005opj]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bacteroides thetaiotaomicron''
| {{Smallcaps|l}}-arabinose
| '''Glu320'''
| Cys416
| <cite>Luis2018</cite>
|-
| [[GH147]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH148]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH149]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH156]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00006s0e pdb_00006s0e]
| exo-α-sialidase
| uncultured bacterium pG7
| N-acetyl-2,3-dehydro-2-deoxyneuraminic acid
| '''His134''' (relay from Asp132)
| Asp14
| <cite>Bule2019</cite>
|-
| [[GH157]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH158]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH161]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH162]]
| S
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00006imw pdb_00006imw]
| endo-β-1,2-glucanase
| ''Talaromyces funiculosus''
| beta-1,2-glucan
| '''Glu262''' via C3-OH of glc at subs. +2
| Asp446
| <cite>Tanaka2019</cite>
|-
| [[GH164]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00006t75 pdb_00006t75]
| β-mannosidase
| ''Bacteroides salyersiae''
| 2-deoxy-2-F-mannosyl
| '''Glu160'''
| Glu297
| <cite>Armstrong2020</cite>
|-
| [[GH167]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
| |

|

|-
| [[GH168]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00008ya7 pdb_00008ya7]
| endo-α-1,3-{{Smallcaps|l}}-fucanase (Fun168A)
| ''Wenyingzhuangia fucanilytica'' CZ1127
| sulfated fucotetraose
| '''Glu264'''
| Asp206
| <cite>Chen2024</cite>
|-
| [[GH169]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH172]]
| none
| β-jelly roll
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00007v1w pdb_00007v1w]
| difructose-anhydride synthase
| ''Bifidobacterium dentum''
| beta-{{Smallcaps|d}}-arabinofuranose
| '''Glu270'''
| Glu291
| <cite>Kashima2021</cite>
|-
| [[GH173]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH178]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at e.g. GH15''
|
|
|
|
|
|
|-
| [[GH181]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00008axi pdb_00008axi]
| exo-α-sialidase
| ''Akkermansia muciniphila''
| 2-deoxy-2,3-dehydro-''N''-acetyl-neuraminic acid + T-antigen disaccharide
| '''Asp345'''
| Glu218
| <cite>Shuoker2023</cite>
|-
| [[GH183]]
| none
| 5-bladed β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00008ic1 pdb_00008ic1]
| endo-α-1,5-{{Smallcaps|d}}-arabinofuranosidase
| ''Microbacterium arabinogalactanolyticum'' JCM 9171
| α-{{Smallcaps|d}}-Araf-(1,5)-α-{{Smallcaps|d}}-Araf-(1,5)-α-{{Smallcaps|d}}-Araf-(1,5)-α-{{Smallcaps|d}}-Araf
| '''Asp51'''
| Asp33
| <cite>Shimokawa2023</cite>
|-
| [[GH186]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00008ip1 pdb_00008ip1]
| β-1,2-glucanase
| ''Escherechia coli''
| β-1,2-glucan
| '''Asp388'''
| Asp300 + 3 waters
| <cite>Motouchi2023</cite>
|-
| [[GH192]]
| S
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at e.g. GH144''
|
|
|
|
|
|
|-
| [[GH193]]
| S
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at e.g. GH144''
|
|
|
|
|
|
|-
| [[GH194]]
| S
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at e.g. GH144''
|
|
|
|
|
|
|-
| [http://www.cazy.org/GH0.html n.c.*]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00002vjj pdb_00002vjj]
| endo-α-N-acetylglucosaminidase
| Bacteriophage HK620
| O18A1 O-antigen hexasaccharide
| '''Asp339'''
| Glu372
| <cite>Barbirz2008</cite>
|}
<nowiki>*</nowiki> n.c.: Found among the collection of [http://www.cazy.org/GH0.html non-classified GH sequences in the CAZy Database].

== References ==

<biblio>
# HeightmanVasella1999 Heightman TD and Vasella AT. ''Recent Insights into Inhibition, Structure, and Mechanism of Configuration-Retaining Glycosidases.'' Angew Chem Int Ed. 1999 38(6):750-770. [http://www3.interscience.wiley.com/journal/55000581/abstract Article online].
# Nerinckx2005 pmid=15642336
# Wu2012 pmid=23137336
# Perez1978 Pérez S and Marchessault RH. ''The exo-anomeric effect: experimental evidence from crystal structures.'' Carbohydr res. 1978 65:114-120. [http://dx.doi.org/10.1016/S0008-6215(00)84218-4 DOI:10.1016/S0008-6215(00)84218-4]
# Cramer1997 Cramer CJ, Truhlar DG, and French AD. ''Exo-anomeric effects on energies and geometries of different conformations of glucose and related systems in the gas phase and aqueous solution.'' Carbohydr res. 1997 298:1-14. [http://dx.doi.org/10.1016/S0008-6215(96)00297-2 DOI:10.1016/S0008-6215(96)00297-2]
# Johnson2009 pmid=19733839
# Alonso2016 pmid=26889578
# Gloster2006 pmid=17002288
# van_Bueren2009 pmid=18976664
# Hrmova2001 pmid=11709165
# Rajan2004 pmid=15341727
# Varrot2003 pmid=12595701
# Zhou1999 pmid=10508787
# Sulzenbacher1999 pmid=10200171
# Urbanikova2011 pmid=21501386
# Guerin2002 pmid=11884144
# Schubot2004 pmid=14756552
# Suzuki2009 pmid=19279191
# Wan2014 pmid=24419374
# Sandgren2004 pmid=15364577
# Uitdehaag1999 pmid=10331869
# Miyake2003 pmid=12741813
# Harris1993 pmid=8431441
# Allouch2004 pmid=15062085
# Wojtkowiak2013 pmid=23275163
# Papanikolau2001 pmid=11560481
# Prag2000 pmid=10884356
# Vocadlo2001 pmid=11518970
# Karlsen1996 pmid=15299731
# Baldwin1993 pmid=8259514
# Cartmell2008 pmid=18799462
# Fernandez-Leiro2010 pmid=20592022
# Abbott2007 pmid=17397864
# Sakurama2012 pmid=22451675
# Sim2008 pmid=18036614
# Verhaest2007 pmid=17335500
# Amaya2004 pmid=15130470
# Zhu2012 pmid=23015718
# Maksimainen2011 pmid=21130883
# Merceron2012 pmid=23012371
# Gibson2007 pmid=17455176
# Shah2008 pmid=18599462
# Czjzek2005 pmid=16212978
# Godoy2016 pmid=27685756
# Fujimoto2010 pmid=20739278
# Kitago2007 pmid=17905739
# Davies1996 pmid=15299721
# Lyu2014 pmid=24766439
# Karaveg2005 pmid=15713668
# Nerinckx2008 pmid=18619586
# Pluvinage2013 pmid=23921382
# Yuan2005 pmid=15893670
# Hoevel2003 pmid=14517232
# Espina2014 pmid=24816105
# Le_Nours2009 pmid=19089956
# Miyanaga2004 pmid=15292273
# Bianchetti2015 pmid=25752603
# Markovic-Housley2000 pmid=11080624
# Imamura2003 pmid=12618437
# Hill2013 pmid=24297913
# Maehara2014 pmid=24482228
# Miyazaki2016 pmid=27688023
# Touhara2014 pmid=24828502
# Suzuki2016 pmid=26494689
# Golan2004 pmid=14573597
# Meng2003 pmid=14517548
# Ito2011 pmid=21354427
# Hurtado-Gerrero2009 pmid=19097997
# Yaoi2007 pmid=17498741
# Martinez-Caballero2023 pmid=37418323
# Thompson2015 pmid=25772148
# Barends2007 pmid=17420245
# Fujimoto2013 pmid=23486481
# Wu2015 pmid=26575439
# Pluvinage2017 pmid=28781080
# Dennis2006 pmid=16565725
# Abbott2009 pmid=19181667
# Hehemann_1_2012 pmid=23150581
# Ficko-Blean2008 pmid=18443291
# Zhu2009 pmid=20081828
# Sogabe2011 pmid=21543843
# Nam2015 pmid=26041776
# Nagae2007 pmid=17459873
# Kitamura2008 pmid=18981178
# Higgins2009 pmid=19608744
# van_Straaten2007 pmid=17502382
# van_Asselt2000 pmid=10684641
# Ndeh2017 pmid=28329766
# Labourel2019 pmid=30877196
# Nakajima2024 Nakajima M. et al. ''Extensive distribution of β-1,2-glucanases: finding of new glycoside hydrolase families of β-1,2-glucanases.'' BioRxiv preprint 2024. https://doi.org/10.1101/2024.02.06.578578
# Luis2018 pmid=29255254
# Bule2019 pmid=31645552
# Jin2016 Jin Y, Petricevic M, John A, Raich L, Jenkins H, Portela De Souza L, Cuskin F, Gilbert HJ, Rovira C, Goddard-Borger ED, Williams SJ, and Davies GJ. ''A β-Mannanase with a Lysozyme-like Fold and a Novel Molecular Catalytic Mechanism.'' ACS Cent Sci. 2016 Nov [http://dx.doi.org/10.1021/acscentsci.6b00232 DOI:10.1021/acscentsci.6b00232]
# Yamada2017 pmid=28392148
# Ohnuma2014 pmid=24582745
# Thompson2012 pmid=22219371
# Xie2016 pmid=27777307
# Gregg2015 pmid=26304114
# Williams2014 pmid=24339341
# Pengthaisong2023 pmid=37180965
# Hehemann_2_2012 pmid=22393053
# Huang2012 pmid=22992047
# Noach2016 pmid=27038508
# Urresti2018 pmid=30084399
# Alonso-Gil2016 pmid=28026180
# Huang2014 Huang CH, Zhu Z, Cheng YS, Chan HC, Ko TP, Chen CC, Wang I, Ho MR, Hsu ST, Zeng YF, Huang YN, Liu JR, Guo RT. ''Structure and Catalytic Mechanism of a Glycoside Hydrolase Family-127 β-L-Arabinofuranosidase (HypBA1).'' J Bioprocess Biotech. 2014 4:171 [http://dx.doi.org/10.4172/2155-9821.1000171 DOI:10.4172/2155-9821.1000171]
# Tsuda2015 pmid=26632508
# Zhai2016 pmid=27088557
# Barbirz2008 pmid=18547389
# Tanaka2019 pmid=30926603
# Armstrong2020 pmid=31871050
# Chen2024 pmid=38795894
# Santos2020 pmid=32451508
# Sato2017 pmid=28546425
# Kashima2021 pmid=34688653
# McGuire2020 pmid=33127644
# Shuoker2023 pmid=37005422
# Shimokawa2023 pmid=37726269
# Motouchi2023 pmid=37735577
</biblio>
[[Category:Definitions and explanations]]

Syn/anti lateral protonation

2025-10-08T18:18:10Z

Wim Nerinckx: proton donor residue number correction in GH30: Glu165 (not 163)

{{CuratorApproved}}
* [[Author]]: [[User:Wim Nerinckx|Wim Nerinckx]]
* [[Responsible Curator]]: [[User:Spencer Williams|Spencer Williams]]

----

== Overview ==

This page provides a table that summarizes the spatial positioning of the catalytic [[general acid]] residue in the active sites of [[glycoside hydrolase]]s, relative to the substrate. The table below updates those found in the seminal paper on this concept by Heightman and Vasella <cite>HeightmanVasella1999</cite>, and a following paper by Nerinckx ''et al.'' <cite>Nerinckx2005</cite>.

== Background ==

The ''"not from above, but from the side"'' concept of semi-lateral glycosidic oxygen [[General_acid/base|protonation]] by [[glycoside hydrolase]]s was introduced by Heightman and Vasella <cite>HeightmanVasella1999</cite>. It was originally only described for [[Anomeric centre (alpha and beta)|beta]]-equatorial [[glycoside hydrolase]]s, but appears to be equally applicable to enzymes acting on an [[Anomeric centre (alpha and beta)|alpha]]-axial glycosidic bond <cite>Nerinckx2005</cite>. When dividing [[Sub-site nomenclature|subsite -1]] into half-spaces by a plane defined by the glycosidic oxygen and C1' and H1' of the –1 glycoside, many ligand-complexed structures reveal that the [[General_acid/base|proton donor]] is positioned either in the ''syn'' half-space (near the ring-oxygen of the –1 glycoside), or in the ''anti'' half-space (on the opposite side of the ring-oxygen). Members of the same GH [[Families|family]] appear to share a common ''syn'' or ''anti'' [[General_acid/base|protonator]] arrangement and further, this specificity appears to be preserved within [[Clans|Clans]] of [[Families|families]]. This page's compilation of [[Sub-site nomenclature|subsite -1]] occupied complexes shows that about 70% of all GH [[Families|families]] are ''anti'' [[General_acid/base|protonators]].

Closer inspection of crystal structures of [[Sub-site nomenclature|–1/+1 subsite]]-spanning substrates, or substrate-analogue ligands, in complex with enzymes reveals a further intriguing corollary <cite>Nerinckx2005 Wu2012</cite>. In substrate-bound complexes with ''anti'' [[General_acid/base|protonating]] GH enzymes, the scissile [[Anomeric centre (alpha and beta)|anomeric bond]] (often studied using the thio-analogue) shows a dihedral angle φ (O5'-C1'-[O,S]x-Cx) that is in the lowest-energy synclinal (gauche) conformation. The rationale for this is that a minus synclinal dihedral angle φ for an equatorial glycosidic bond, or plus synclinal for an axial glycosidic bond <cite>Perez1978</cite>, allows for hyperconjugative overlap of the C1'-O5' antibonding orbital with an antiperiplanar-oriented lone pair orbital lobe of the glycosidic oxygen, thereby creating partial double bond character and stabilization of the glycosidic bond by 4–5 kcal/mol; this ground-state stabilizing phenomenon is known as the ‘exo-anomeric effect’ <cite>Cramer1997 Johnson2009 Alonso2016</cite>. ''Anti'' [[General_acid/base|protonation]] occurs on the glycosidic oxygen’s antiperiplanar lone pair, thereby removing the stabilizing exo-anomeric effect. This suggests that ''anti'' [[General_acid/base|protonation]] is an enzymic approach for lowering the activation barrier leading to the [[Transition state|transition state]] (Figure 1 centre).

''Syn'' [[General_acid/base|protonating]] [[glycoside hydrolase]]s apparently make use of a different approach <cite>Nerinckx2005 Wu2012</cite>. In many [[Sub-site nomenclature|–1/+1 subsite]]-spanning ligand complexes, the dihedral angle φ of the scissile anomeric bond has been rotated away from its lowest-energy synclinal position: clockwise to minus-anticlinal or antiperiplanar for beta-equatorial; counterclockwise to plus-anticlinal or antiperiplanar for alpha-axial [[Anomeric centre (alpha and beta)|anomeric bonds]]. This removes the hyperconjugative overlap and thus also the stabilizing exo-anomeric effect. And because of this rotation, a lone pair of the glycosidic oxygen is directed into the ''syn'' half-space, allowing it to be protonated by the ''syn''-positioned [[General_acid/base|proton donor]] (Figure 1 right).

[[File:Syn_anti.jpg|800px|thumb|center|Figure 1. Newman projections, with the glycosidic oxygen as proximal atom and the anomeric carbon as distal atom, showing ''anti'' (centre) versus ''syn'' (right) semi-lateral [[General_acid/base|protonation]] in beta-equatorial (top) and alpha-axial (bottom) [[glycoside hydrolase]]s. The indicated φ is the dihedral angle for O5'-C1'-O4-C4.]]

== Table of ''syn/anti'' protonation examples ==

This table contains only one example per GH [[Families|family]] of a ligand-complexed protein structure where the ''syn'' or ''anti'' positioning of the [[General_acid/base|proton donor]] can be clearly observed; other examples may be available on a [[Families|family-by-family]] basis. The reader is thus advised to consult the [http://www.cazy.org/fam/acc_GH.html#table CAZy database] for a current, comprehensive list of CAZyme structures. Where available, the selected examples are Michaelis-type complexes with the ligand spanning the [[Sub-site nomenclature|-1/+1 subsites]], since these have an intact glycosidic or thioglycosidic bond, or are ''N''-analogs of the substrate (''e.g.'' acarbose). In some examples, the [[General_acid/base|proton donor]] has been mutated (''e.g.'', to the corresponding amide or to an alanine), and in those cases one may wish to look at a superposition of the given PDB example with the structure of the native enzyme. If a Michaelis-type complex is not yet available, the second and third example choices, respectively, are trapped glycosyl-enzyme [[intermediate]]s and product complexes where [[Sub-site nomenclature|subsite -1]] is occupied.

''Please also be aware that this is a large table with many data. Please contact the page Author or Responsible Curator with corrections.''

=== Table ===
This table can be re-sorted by clicking on the icons in the header (''javascript must be turned on in your browser''). To reset the page to be sorted by GH family, click the ''View'' tab at the very top of the page.

{| {{Prettytable}} class="sortable"
|- valign="top"
! '''Family'''
! '''Clan'''
! '''Structure fold '''
! '''Anomeric specificity'''
! '''Mechanism'''
! '''''Syn/anti'' protonator'''
! '''Example PDB ID'''
! '''Enzyme'''
! '''Organism'''
! '''Ligand'''
! '''General acid'''
! '''Nucleophile or General base'''
! '''Reference'''
|-
| [[GH1]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002cer pdb_00002cer]
| β-glycosidase S
| ''Sulfolobus solfataricus'' P2
| phenethyl glucoimidazole
| '''Glu206'''
| Glu387
| <cite>Gloster2006</cite>
|-
| [[GH2]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002vzu pdb_00002vzu]
| exo-β-glucosaminidase
| ''Amicolatopsis orientalis''
| PNP-β-{{Smallcaps|d}}-glucosamine
| '''Glu469'''
| Glu541
| <cite>van_Bueren2009</cite>
|-
| [[GH3]]
| none
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001iex pdb_00001iex]
| exo-1,3-1,4-glucanase
| ''Hordeum vulgare''
| thiocellobiose
| '''Glu491'''
| Asp285
| <cite>Hrmova2001</cite>
|-
| [[GH4]]
| none
| Rossmann + α6/β3 + β3/α4
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001u8x pdb_00001u8x]
| 6-P-α-glucosidase
| ''Bacillus subtilis''
| alpha-{{Smallcaps|d}}-glucose-6-phosphate
| '''Asp172'''
| not applicable
| <cite>Rajan2004</cite>
|-
| [[GH5]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001h2j pdb_00001h2j]
| endo-β-1,4-glucanase
| ''Bacillus agaradhaerens''
| 2',4'-DNP-2-F-cellobioside
| '''Glu129'''
| Glu228
| <cite>Varrot2003</cite>
|-
| [[GH6]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00001qjw pdb_00001qjw]
| cellobiohydrolase 2
| ''Hypocrea jecorina''
| (Glc)2-S-(Glc)2
| '''Asp221'''
| debated
| <cite>Zhou1999</cite>
|-
| [[GH7]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00001ovw pdb_00001ovw]
| endo-1,4-glucanase
| ''Fusarium oxysporum''
| thio-(Glc)5
| '''Glu202'''
| Glu197
| <cite>Sulzenbacher1999</cite>
|-
| [[GH8]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00001kwf pdb_00001kwf]
| endo-1,4-glucanase
| ''Clostridium thermocellum''
| cellopentaose
| '''Glu95'''
| Asp278
| <cite>Guerin2002</cite>
|-
| [[GH9]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00001rq5 pdb_00001rq5]
| cellobiohydrolase
| ''Clostridium thermocellum''
| cellotetraose
| '''Glu795'''
| Asp383
| <cite>Schubot2004</cite>
|-
| [[GH10]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002d24 pdb_00002d24]
| β-1,4-xylanase
| ''Streptomyces olivaceoviridis'' E-86
| xylopentaose
| '''Glu128'''
| Glu236
| <cite>Suzuki2009</cite>
|-
| [[GH11]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00004hk8 pdb_00004hk8]
| endo-β-1,4-xylanase
| ''Hypocrea jecorina''
| xylohexaose
| '''Glu177'''
| Glu86
| <cite>Wan2014</cite>
|-
| [[GH12]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00001w2u pdb_00001w2u]
| endoglucanase
| ''Humicola grisea''
| thiocellotetraose
| '''Glu205'''
| Glu120
| <cite>Sandgren2004</cite>
|-
| [[GH13]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001cxk pdb_00001cxk]
| β-cyclodextrin glucanotransferase
| ''Bacillus circulans''
| maltononaose
| '''Glu257'''
| Asp229
| <cite>Uitdehaag1999</cite>
|-
| [[GH14]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00001itc pdb_00001itc]
| β-amylase
| ''Bacillus cereus''
| maltopentaose
| '''Glu172'''
| Glu367
| <cite>Miyake2003</cite>
|-
| [[GH15]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00001dog pdb_00001dog]
| glucoamylase
| ''Aspergillus awamori''
| 1-deoxynojirimycin
| '''Glu179'''
| Glu400
| <cite>Harris1993</cite>
|-
| [[GH16]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00001urx pdb_00001urx]
| β-agarase A
| ''Zobellia galactanivorans''
| oligoagarose
| '''Glu152'''
| Glu147
| <cite>Allouch2004</cite>
|-
| [[GH17]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00004gzj pdb_00004gzj]
| endo-β-1,3-glucanase
| ''Solanum tuberosum''
| laminaratriose + laminarabiose
| '''Glu118'''
| Glu259
| <cite>Wojtkowiak2013</cite>
|-
| [[GH18]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001ffr pdb_00001ffr]
| chitinase A
| ''Serratia marcescens''
| (NAG)6
| '''Glu315'''
| internal
| <cite>Papanikolau2001</cite>
|-
| [[GH19]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00003wh1 pdb_00003wh1]
| chitinase
| ''Bryum coronatum''
| (GlcNAc)4
| '''Glu61'''
| Glu70
| <cite>Ohnuma2014</cite>
|-
| [[GH20]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001c7s pdb_00001c7s]
| chitobiase
| ''Serratia marcescens''
| chitobiose
| '''Glu540'''
| internal
| <cite>Prag2000</cite>
|-
| [[GH22]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00001h6m pdb_00001h6m]
| lysozyme C
| ''Gallus gallus''
| Chit-2-F-chitosyl
| '''Glu35'''
| Asp52
| <cite>Vocadlo2001</cite>
|-
| [[GH23]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00001lsp pdb_00001lsp]
| lysozyme G
| ''Cygnus atratus''
| Bulgecin A
| '''Glu73'''
| internal
| <cite>Karlsen1996</cite>
|-
| [[GH24]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_0000148l pdb_0000148l]
| lysozyme E
| Bacteriophage T4
| chitobiosyl
| '''Glu11'''
| Glu26
| <cite>Baldwin1993</cite>
|-
| [[GH26]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002vx6 pdb_00002vx6]
| exo-β-mannanase
| ''Cellvibrio japonicus'' Ueda107
| Gal1Man4
| '''Glu221'''
| Glu338
| <cite>Cartmell2008</cite>
|-
| [[GH27]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}} / beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00003lrm pdb_00003lrm]
| α-galactosidase
| ''Saccharomyces cerevisiae''
| raffinose
| '''Asp209'''
| Asp141
| <cite>Fernandez-Leiro2010</cite>
|-
| [[GH28]]
| N
| β-helix
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00002uvf pdb_00002uvf]
| exo-polygalacturonosidase
| ''Yersinia enterocolitica'' ATCC9610D
| digalacturonic acid
| '''Asp402'''
| Asp381 Asp403
| <cite>Abbott2007</cite>
|-
| [[GH29]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00003uet pdb_00003uet]
| α-1,3/4-fucosidase
| ''Bifidobacterium longum'' subsp. infantis
| lacto-''N''-fucopentaose II
| '''Glu217'''
| Asp172
| <cite>Sakurama2012</cite>
|-
| [[GH30]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002y24 pdb_00002y24]
| glucurono-xylanase
| ''Dickea chrysanthemi'' D1
| glucuronoxylan tetrasaccharide
| '''Glu165'''
| Glu253
| <cite>Urbanikova2011</cite>
|-
| [[GH31]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002qmj pdb_00002qmj]
| maltase-glucoamylase
| ''Homo sapiens''
| acarbose
| '''Asp542'''
| Asp443
| <cite>Sim2008</cite>
|-
| [[GH32]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002add pdb_00002add]
| fructan β-(2,1)-fructosidase
| ''Cichorium intybus''
| sucrose
| '''Glu201'''
| Asp22
| <cite>Verhaest2007</cite>
|-
| [[GH33]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001s0i pdb_00001s0i]
| transsialidase
| ''Trypanosoma cruzi''
| sialyllactose
| '''Asp59'''
| Tyr342 (with Glu230)
| <cite>Amaya2004</cite>
|-
| [[GH34]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00004gzw pdb_00004gzw]
| N2 neuraminidase
| ''Influenza'' A Tanzania/205/2010 H3N2
| α-{{Smallcaps|d}}-Neup5Ac-(2,3)-β-{{Smallcaps|d}}-Galp-(1,4)-β-{{Smallcaps|d}}-GlcpNAc
| '''Asp151'''
| Tyr406 (with Glu277)
| <cite>Zhu2012</cite>
|-
| [[GH35]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00003ogv pdb_00003ogv]
| β-galactosidase
| ''Hypocrea jecorina''
| 2-phenylethyl 1-thio-β-{{Smallcaps|d}}-galactopyranoside
| '''Glu200'''
| Glu298
| <cite>Maksimainen2011</cite>
|-
| [[GH36]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00004fnu pdb_00004fnu]
| β-galactosidase
| ''Geobacillus stearothermophilus''
| stachyose
| '''Asp584'''
| Asp478
| <cite>Merceron2012</cite>
|-
| [[GH37]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00002jf4 pdb_00002jf4]
| trehalase
| ''Escherichia coli''
| validoxylamine
| '''Asp312'''
| Glu496
| <cite>Gibson2007</cite>
|-
| [[GH38]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00003czn pdb_00003czn]
| Golgi α-mannosidase II
| ''Drosophila melanogaster''
| GlcNAcMan(5)GlcNAc(2)
| '''Asp341'''
| Asp204
| <cite>Shah2008</cite>
|-
| [[GH39]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002bfg pdb_00002bfg]
| β-xylosidase
| ''Geobacillus stearothermophilus''
| 2,5-dinitrophenyl-β-{{Smallcaps|d}}-xyloside
| '''Glu160'''
| Glu278
| <cite>Czjzek2005</cite>
|-
| [[GH42]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00004ucf pdb_00004ucf]
| β-galactosidase
| ''Bifidobacterium bifidum''
| {{Smallcaps|d}}-galactose
| '''Glu161'''
| Glu320
| <cite>Godoy2016</cite>
|-
| [[GH43]]
| F
| 5-fold β-propeller
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00003akh pdb_00003akh]
| exo-1,5-α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces avermitilis''
| α-1,5-arabinofuranotriose
| '''Glu196'''
| Asp220
| <cite>Fujimoto2010</cite>
|-
| [[GH44]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002eqd pdb_00002eqd]
| endoglucanase
| ''Clostridium thermocellum''
| cellooctaose
| '''Glu186'''
| Glu359
| <cite>Kitago2007</cite>
|-
| [[GH45]]
| none
| 6-stranded β-barrel
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00004eng pdb_00004eng]
| endo-1,4-glucanase
| ''Humicola insolens''
| cellohexaose
| '''Asp121'''
| Asp10
| <cite>Davies1996</cite>
|-
| [[GH46]]
| I
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00004olt pdb_00004olt]
| chitosanase
| ''Microbacterium sp.'' OU01
| hexa-glucosamine
| '''Glu25'''
| Asp43
| <cite>Lyu2014</cite>
|-
| [[GH47]]
| none
| (α/α)7
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00001x9d pdb_00001x9d]
| α-mannosidase I
| ''Homo sapiens''
| Me-2-S-(α-Man)-2-thio-α-Man
| '''Asp463'''
| Glu599
| <cite>Karaveg2005</cite>, <cite>Nerinckx2008</cite>
|-
| [[GH48]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH8''
|
|
|
|
|
|
|-
| [[GH49]]
| N
| β-helix
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH28''
|
|
|
|
|
|
|-
| [[GH50]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00004bq5 pdb_00004bq5]
| exo-β-agarase
| ''Saccharophagus degradans''
| neoagarotetraose
| '''Glu535'''
| Glu695
| <cite>Pluvinage2013</cite>
|-
| [[GH51]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001qw9 pdb_00001qw9]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Geobacillus stearothermophilus''
| PNP-{{Smallcaps|l}}-arabinofuranoside
| '''Glu175'''
| Glu294
| <cite>Hoevel2003</cite>
|-
| [[GH52]]
| O
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| '' predicted perpendicular by clan, see at GH116''
| [{{PDBlink}}pdb_00004c1p pdb_00004c1p]
| β-xylosidase
| ''Geobacillus thermoglucosidasius''
| xylobiose
| '''Asp517'''
| Glu537
| <cite>Espina2014</cite>
|-
| [[GH53]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002ccr pdb_00002ccr]
| β-1,4-galactanase
| ''Bacillus licheniformis''
| galactotriose
| '''Glu165'''
| Glu263
| <cite>Le_Nours2009</cite>
|-
| [[GH54]]
| none
| β-sandwich
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001wd4 pdb_00001wd4]
| α-{{Smallcaps|l}}-arabinofuranosidase B
| ''Aspergillus kawachii''
| {{Smallcaps|l}}-arabinofuranose
| '''Asp297'''
| Glu221
| <cite>Miyanaga2004</cite>
|-
| [[GH55]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00004tz5 pdb_00004tz5]
| exo-β-1,3-glucanase
| ''Streptomyces sp.'' SirexAA-E
| laminarihexaose
| '''Glu502'''
| unknown
| <cite>Bianchetti2015</cite>
|-
| [[GH56]]
| none
| (β/α)7
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001fcv pdb_00001fcv]
| hyaluronidase
| ''Apis mellifera''
| (hyaluron.)4
| '''Glu113'''
| internal
| <cite>Markovic-Housley2000</cite>
|-
| [[GH57]]
| T
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001k1y pdb_00001k1y]
| glucanotransferase
| ''Thermococcus litoralis''
| acarbose
| '''Asp214'''
| Glu123
| <cite>Imamura2003</cite>
|-
| [[GH59]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00004ccc pdb_00004ccc]
| β-galactocerebrosidase
| ''Mus musculus''
| PNP-β-{{Smallcaps|d}}-galactoside
| '''Glu182'''
| Glu258
| <cite>Hill2013</cite>
|-
| [[GH62]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00003wn0 pdb_00003wn0]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces coelicolor''
| β-{{Smallcaps|l}}-Arabinofuranose
| '''Glu361'''
| Asp202
| <cite>Maehara2014</cite>
|-
| [[GH63]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00005ca3 pdb_00005ca3]
| α-glucosidase
| ''Escherichia coli''
| glucose and lactose
| '''Asp501'''
| Glu727
| <cite>Miyazaki2016</cite>
|-
| [[GH65]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00004ktr pdb_00004ktr]
| 2-O-α-glucosylglycerol phosphorylase
| ''Bacillus selenitireducens''
| isofagomine
| '''Glu475'''
| phosphate
| <cite>Touhara2014</cite>
|-
| [[GH66]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00005axh pdb_00005axh]
| dextranase
| ''Thermoanaerobacter pseudethanolicus''
| isomaltohexaose
| '''Glu374'''
| Asp312
| <cite>Suzuki2016</cite>
|-
| [[GH67]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00001l8n pdb_00001l8n]
| α-glucuronidase
| ''Geobacillus stearothermophilus''
| 4-O-methyl-{{Smallcaps|d}}-glucuronic acid and xylotriose
| '''Glu286'''
| Asp364 Glu392
| <cite>Golan2004</cite>
|-
| [[GH68]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001pt2 pdb_00001pt2]
| levansucrase
| ''Bacillus subtilis''
| sucrose
| '''Glu342'''
| Asp86
| <cite>Meng2003</cite>
|-
| [[GH70]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00003aic pdb_00003aic]
| glucansucrase
| ''Streptococcus mutans''
| α-acarbose
| '''Glu515'''
| Asp477
| <cite>Ito2011</cite>
|-
| [[GH72]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002w62 pdb_00002w62]
| β-1,3-glucanotransferase
| ''Saccharomyces cerevisiae'' S288C
| laminaripentaose
| '''Glu176'''
| Glu275
| <cite>Hurtado-Gerrero2009</cite>
|-
| [[GH73]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| unknown
| '''''syn'''''
| [{{PDBlink}}pdb_00007pod pdb_00007pod]
| peptidoglycan endo-β-1,4-''N''-acetylglucosaminidase
| ''Streptococcus pneumoniae'' R6
| NAG-NAM-NAG-NAM tetrasaccharide
| '''Glu585'''
| unknown
| <cite>Martinez-Caballero2023</cite>
|-
| [[GH74]]
| none
| 7-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00002ebs pdb_00002ebs]
| cellobiohydrolase (OXG-RCBH)
| ''Geotrichum sp.'' m128
| xyloglucan heptasaccharide
| '''Asp465'''
| Asp35
| <cite>Yaoi2007</cite>
|-
| [[GH76]]
| none
| (α/α)6
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00005agd pdb_00005agd]
| endo-α-1,6-mannanase
| ''Bacillus circulans''
| α-1,6-mannopentaose
| '''Asp125'''
| Asp124
| <cite>Thompson2015</cite>
|-
| [[GH77]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002oww pdb_00002oww]
| 4-α-glucanotransferase
| ''Thermus thermofilus''
| acarbose + 4-deoxy-α-{{Smallcaps|d}}-glucose
| '''Glu340'''
| Asp293
| <cite>Barends2007</cite>
|-
| [[GH78]]
| H
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00003w5n pdb_00003w5n]
| α-{{Smallcaps|l}}-rhamnosidase
| ''Streptomyces avermitilis''
| {{Smallcaps|l}}-rhamnose
| '''Glu636'''
| Glu895
| <cite>Fujimoto2013</cite>
|-
| [[GH79]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00005e9c pdb_00005e9c]
| heparanase
| ''Homo sapiens''
| heparin tetrasaccharide
| '''Glu225'''
| Glu343
| <cite>Wu2015</cite>
|-
| [[GH80]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH24''
|
|
|
|
|
|
|-
| [[GH81]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00005t4g pdb_00005t4g]
| endo-β-1,3-glucanase
| ''Bacillus halodurans'' C-125
| laminarin
| '''Asp466'''
| Glu542
| <cite>Pluvinage2017</cite>
|-
| [[GH83]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001z4x pdb_00001z4x]
| hemagglutinin-neuraminidase
| Simian virus 5
| α-2,3-sialyllactose
| '''Asp187''' on flexible loop
| Tyr523 (with Glu390)
| <cite>Yuan2005</cite>
|-
| [[GH84]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002chn pdb_00002chn]
| β-''N''-acetyl-glucosaminidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| NAG-thiazoline
| '''Glu242'''
| internal
| <cite>Dennis2006</cite>
|-
| [[GH85]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002w92 pdb_00002w92]
| endo-β-''N''-acetyl-glucosaminidase D
| ''Streptococcus pneumoniae'' TIGR4
| NAG-thiazoline
| '''Glu337'''
| internal
| <cite>Abbott2009</cite>
|-
| [[GH86]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00004aw7 pdb_00004aw7]
| β-porphyranase
| ''Bacteroides plebeius''
| porphyran fragment
| '''Glu152'''
| Glu279
| <cite>Hehemann_1_2012</cite>
|-
| [[GH89]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002vcb pdb_00002vcb]
| α-''N''-acetyl-glucosaminidase
| ''Clostridium perfringens''
| PUGNAc
| '''Glu483'''
| Glu601
| <cite>Ficko-Blean2008</cite>
|-
| [[GH92]]
| none
| (α/α)6 and β-sandwich
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00002ww1 pdb_00002ww1]
| α-1,2-mannosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| thiomannobioside
| '''Glu533'''
| Asp644 Asp642
| <cite>Zhu2009</cite>
|-
| [[GH93]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00003a72 pdb_00003a72]
| exo-arabinanase
| ''Penicillium chrysogenum''
| arabinobiose
| '''Glu246'''
| Glu174
| <cite>Sogabe2011</cite>
|-
| [[GH94]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00004zli pdb_00004zli]
| cellobionic acid phosphorylase
| ''Saccharophagus degradans''
| 3-O-β-{{Smallcaps|d}}-glucopyranosyl-α-{{Smallcaps|d}}-glucopyranuronic acid
| '''Asp472'''
| phosphate
| <cite>Nam2015</cite>
|-
| [[GH95]]
| none
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00002ead pdb_00002ead]
| α-1,2-{{Smallcaps|l}}-fucosidase
| ''Bifidobacterium bifidum''
| Fuc-α-1,2-Gal
| '''Glu566'''
| Asn423 Asp766
| <cite>Nagae2007</cite>
|-
| [[GH97]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining + inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00002zq0 pdb_00002zq0]
| α-glucosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| acarbose
| '''Glu532'''
| Glu508
| <cite>Kitamura2008</cite>
|-
| [[GH98]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00002wmg pdb_00002wmg]
| endo-β-1,4-galactosidase
| ''Streptococcus pneumoniae''
| A-LewisY pentasaccharide
| '''Glu158'''
| Asp251 Glu301
| <cite>Higgins2009</cite>
|-
| [[GH99]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00004ad4 pdb_00004ad4]
| endo-α-mannosidase
| ''Bacteroides xylanisolvens''
| glucose-1,3-isofagomine and α-1,2- mannobiose
| '''Glu336'''
| debated
| <cite>Thompson2012</cite>
|-
| [[GH100]]
| G
| (α/α)6 core
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00005gop pdb_00005gop]
| invertase
| ''Anabaena (Nostoc) sp.'' pcc7120
| sucrose
| '''Asp188'''
| Glu414
| <cite>Xie2016</cite>
|-
| [[GH101]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00005a56 pdb_00005a56]
| endo-α-N-acetylgalactosaminidase
| ''Streptococcus pneumoniae'' TIGR4
| β-{{Smallcaps|d}}-Galp-(1-3)-α-{{Smallcaps|d}}-GalpNAc-(1)-methyl
| '''Glu796''' +water
| Asp764
| <cite>Gregg2015</cite>
|-
| [[GH102]]
| none
| double-ψ β-barrel
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00002pi8 pdb_00002pi8]
| lytic transglycosylase A
| ''Escherichia coli''
| chitohexaose
| '''Asp308'''
| none
| <cite>van_Straaten2007</cite>
|-
| [[GH103]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00001d0k pdb_00001d0k]
| lytic transglycosylase SLT35
| ''Escherichia coli''
| murodipeptides
| '''Glu162'''
| internal
| <cite>van_Asselt2000</cite>
|-
| [[GH106]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00005mwk pdb_00005mwk]
| α-{{Smallcaps|l}}-rhamnosidase BT_0986
| ''Bacteroides thetaiotaomicron''
| pectin heptasaccharide
| '''Glu461'''
| Glu593 or Glu561
| <cite>Ndeh2017</cite>
|-
| [[GH107]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| ''predicted syn by clan''
| ''see at GH29''
|
|
|
|
|
|
|-
| [[GH110]]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00007jwf pdb_00007jwf]
| α-1,3-galactosidase
| ''Pseudoalteromonas distincta''
| Gal-α1,3-Gal
| '''Asp344'''
| Asp321 Asp345
| <cite>McGuire2020</cite>
|-
| [[GH113]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00004cd8 pdb_00004cd8]
| β-mannanase
| ''Alicyclobacillus acidocaldarius''
| mannobioimidazole
| '''Glu151'''
| Glu231
| <cite>Williams2014</cite>
|-
| [[GH116]]
| O
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''perpendicular''''' (anomaly)
| [{{PDBlink}}pdb_00008i5u pdb_00008i5u]
| β-glucosidase
| ''Thermoanaerobacterium xylanolyticum'' LX-11
| laminaribiose
| '''Asp593'''
| Glu441
| <cite>Pengthaisong2023</cite>
|-
| [[GH117]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00004ak7 pdb_00004ak7]
| α-1,3-3,6-anhydro-{{Smallcaps|l}}-galactosidase
| ''Bacteroides plebeius''
| neoagarobiose
| '''His302''' (relay from Asp320)
| Asp90
| <cite>Hehemann_2_2012</cite>
|-
| [[GH119]]
| T
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at GH57''
|
|
|
|
|
|
|-
| [[GH120]]
| none
| parallel β-helix and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00003vsv pdb_00003vsv]
| β-xylosidase XylC
| ''Thermoanaerobacterium saccharolyticum'' JW/SL-YS485
| {{Smallcaps|d}}-xylose
| '''Glu405'''
| Asp382
| <cite>Huang2012</cite>
|-
| [[GH123]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00005fr0 pdb_00005fr0]
| exo-β-N-acetyl-galactosaminidase
| ''Clostridium perfringens''
| ''N''-difluoroacetyl-{{Smallcaps|d}}-galactosamine
| '''Glu345'''
| internal
| <cite>Noach2016</cite>
|-
| [[GH124]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00006g1i pdb_00006g1i]
| endo-β-1,4-glucanase
| ''Acetivibrio thermocellus'' ATCC 27405
| fructosylated cellopentaose
| '''Glu203'''
| unknown
| <cite>Urresti2018</cite>
|-
| [[GH125]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00005m7y pdb_00005m7y]
| exo-α-1,6-mannosidase
| ''Clostridium perfringens''
| 1,6-α-mannotriose
| '''Asp220'''
| Glu393
| <cite>Alonso-Gil2016</cite>
|-
| [[GH127]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00003wrg pdb_00003wrg]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bifidobacterium longum''
| {{Smallcaps|l}}-arabinose
| '''Glu322'''
| Cys417
| <cite>Huang2014</cite>
|-
| [[GH128]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00006ufl pdb_00006ufl]
| β-1,3-glucanase
| ''Amycolatopsis mediterranei''
| laminarihexaose
| '''Glu102'''
| Glu199
| <cite>Santos2020</cite>
|-
| [[GH129]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00005wzn pdb_00005wzn]
| exo-α-''N''-acetylgalactosaminidase (NagBb)
| ''Bifidobacterium bifidum'' JCM 1254
| GalNAc
| '''Glu478'''
| Asp435
| <cite>Sato2017</cite>
|-
| [[GH130]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00005b0s pdb_00005b0s]
| β-1,2-mannobiose phosphorylase
| ''Listeria innocua''
| β-1,2-mannotriose
| '''Asp141''' relay
| phosphate
| <cite>Tsuda2015</cite>
|-
| [[GH133]]
| none
| (α/α)6
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00005d0f pdb_00005d0f]
| glycogen-debranching enzyme
| ''Nakaseomyces glabratus'' CBS 138
| maltopentaose
| '''Glu564'''
| Asp535
| <cite>Zhai2016</cite>
|-
| [[GH134]]
| none
| β + α
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00005jug pdb_00005jug]
| β-mannanase
| ''Streptomyces sp.''
| mannopentaose
| '''Glu45'''
| Asp57
| <cite>Jin2016</cite>
|-
| [[GH136]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00005gqf pdb_00005gqf]
| lacto-N-biosidase
| ''Bifidobacterium longum''
| lacto-N-biose
| '''Asp411'''
| Asp418
| <cite>Yamada2017</cite>
|-
| [[GH137]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|l}}
| unknown
| '''''anti'''''
| [{{PDBlink}}pdb_00005mui pdb_00005mui]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0996
| ''Bacteroides thetaiotaomicron''
| pectin oligosaccharide
| '''Glu240'''
| Glu159
| <cite>Ndeh2017</cite>
|-
| [[GH138]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00006hzg pdb_00006hzg]
| α-1,2-{{Smallcaps|d}}-galacturonidase
| ''Bacteroides paurosaccharolyticus''
| alpha-{{Smallcaps|d}}-galactopyranuronic
| '''Glu294'''
| Glu361
| <cite>Labourel2019</cite>
|-
| [[GH140]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH144]]
| S
| (α/α)8
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00008xul pdb_00008xul]
| beta-1,2-glucanase
| ''Xanthomonas campestris''
| beta-1,2-glucoheptasaccharide
| '''Glu239'''
| unknown
| <cite>Nakajima2024</cite>
|-
| [[GH146]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00005opj pdb_00005opj]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bacteroides thetaiotaomicron''
| {{Smallcaps|l}}-arabinose
| '''Glu320'''
| Cys416
| <cite>Luis2018</cite>
|-
| [[GH147]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH148]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH149]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH156]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00006s0e pdb_00006s0e]
| exo-α-sialidase
| uncultured bacterium pG7
| N-acetyl-2,3-dehydro-2-deoxyneuraminic acid
| '''His134''' (relay from Asp132)
| Asp14
| <cite>Bule2019</cite>
|-
| [[GH157]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH158]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH161]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH162]]
| S
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00006imw pdb_00006imw]
| endo-β-1,2-glucanase
| ''Talaromyces funiculosus''
| beta-1,2-glucan
| '''Glu262''' via C3-OH of glc at subs. +2
| Asp446
| <cite>Tanaka2019</cite>
|-
| [[GH164]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00006t75 pdb_00006t75]
| β-mannosidase
| ''Bacteroides salyersiae''
| 2-deoxy-2-F-mannosyl
| '''Glu160'''
| Glu297
| <cite>Armstrong2020</cite>
|-
| [[GH167]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|-
| [[GH168]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00008ya7 pdb_00008ya7]
| endo-α-1,3-{{Smallcaps|l}}-fucanase (Fun168A)
| ''Wenyingzhuangia fucanilytica'' CZ1127
| sulfated fucotetraose
| '''Glu264'''
| Asp206
| <cite>Chen2024</cite>
|-
| [[GH169]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH172]]
| none
| β-jelly roll
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00007v1w pdb_00007v1w]
| difructose-anhydride synthase
| ''Bifidobacterium dentum''
| beta-{{Smallcaps|d}}-arabinofuranose
| '''Glu270'''
| Glu291
| <cite>Kashima2021</cite>
|-
| [[GH173]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH178]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at e.g. GH15''
|
|
|
|
|
|-
| [[GH181]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00008axi pdb_00008axi]
| exo-α-sialidase
| ''Akkermansia muciniphila''
| 2-deoxy-2,3-dehydro-''N''-acetyl-neuraminic acid + T-antigen disaccharide
| '''Asp345'''
| Glu218
| <cite>Shuoker2023</cite>
|-
| [[GH183]]
| none
| 5-bladed β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00008ic1 pdb_00008ic1]
| endo-α-1,5-{{Smallcaps|d}}-arabinofuranosidase
| ''Microbacterium arabinogalactanolyticum'' JCM 9171
| α-{{Smallcaps|d}}-Araf-(1,5)-α-{{Smallcaps|d}}-Araf-(1,5)-α-{{Smallcaps|d}}-Araf-(1,5)-α-{{Smallcaps|d}}-Araf
| '''Asp51'''
| Asp33
| <cite>Shimokawa2023</cite>
|-
| [[GH186]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00008ip1 pdb_00008ip1]
| β-1,2-glucanase
| ''Escherechia coli''
| β-1,2-glucan
| '''Asp388'''
| Asp300 + 3 waters
| <cite>Motouchi2023</cite>
|-
| [http://www.cazy.org/GH0.html n.c.*]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00002vjj pdb_00002vjj]
| endo-α-N-acetylglucosaminidase
| Bacteriophage HK620
| O18A1 O-antigen hexasaccharide
| '''Asp339'''
| Glu372
| <cite>Barbirz2008</cite>
|}
<nowiki>*</nowiki> n.c.: Found among the collection of [http://www.cazy.org/GH0.html non-classified GH sequences in the CAZy Database].

== References ==

<biblio>
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# Ndeh2017 pmid=28329766
# Labourel2019 pmid=30877196
# Nakajima2024 Nakajima M. et al. ''Extensive distribution of β-1,2-glucanases: finding of new glycoside hydrolase families of β-1,2-glucanases.'' BioRxiv preprint 2024. https://doi.org/10.1101/2024.02.06.578578
# Luis2018 pmid=29255254
# Bule2019 pmid=31645552
# Jin2016 Jin Y, Petricevic M, John A, Raich L, Jenkins H, Portela De Souza L, Cuskin F, Gilbert HJ, Rovira C, Goddard-Borger ED, Williams SJ, and Davies GJ. ''A β-Mannanase with a Lysozyme-like Fold and a Novel Molecular Catalytic Mechanism.'' ACS Cent Sci. 2016 Nov [http://dx.doi.org/10.1021/acscentsci.6b00232 DOI:10.1021/acscentsci.6b00232]
# Yamada2017 pmid=28392148
# Ohnuma2014 pmid=24582745
# Thompson2012 pmid=22219371
# Xie2016 pmid=27777307
# Gregg2015 pmid=26304114
# Williams2014 pmid=24339341
# Pengthaisong2023 pmid=37180965
# Hehemann_2_2012 pmid=22393053
# Huang2012 pmid=22992047
# Noach2016 pmid=27038508
# Urresti2018 pmid=30084399
# Alonso-Gil2016 pmid=28026180
# Huang2014 Huang CH, Zhu Z, Cheng YS, Chan HC, Ko TP, Chen CC, Wang I, Ho MR, Hsu ST, Zeng YF, Huang YN, Liu JR, Guo RT. ''Structure and Catalytic Mechanism of a Glycoside Hydrolase Family-127 β-L-Arabinofuranosidase (HypBA1).'' J Bioprocess Biotech. 2014 4:171 [http://dx.doi.org/10.4172/2155-9821.1000171 DOI:10.4172/2155-9821.1000171]
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</biblio>
[[Category:Definitions and explanations]]

Syn/anti lateral protonation

2025-08-22T12:10:23Z

Wim Nerinckx: All pdb IDs in the new 12-character format

{{CuratorApproved}}
* [[Author]]: [[User:Wim Nerinckx|Wim Nerinckx]]
* [[Responsible Curator]]: [[User:Spencer Williams|Spencer Williams]]

----

== Overview ==

This page provides a table that summarizes the spatial positioning of the catalytic [[general acid]] residue in the active sites of [[glycoside hydrolase]]s, relative to the substrate. The table below updates those found in the seminal paper on this concept by Heightman and Vasella <cite>HeightmanVasella1999</cite>, and a following paper by Nerinckx ''et al.'' <cite>Nerinckx2005</cite>.

== Background ==

The ''"not from above, but from the side"'' concept of semi-lateral glycosidic oxygen [[General_acid/base|protonation]] by [[glycoside hydrolase]]s was introduced by Heightman and Vasella <cite>HeightmanVasella1999</cite>. It was originally only described for [[Anomeric centre (alpha and beta)|beta]]-equatorial [[glycoside hydrolase]]s, but appears to be equally applicable to enzymes acting on an [[Anomeric centre (alpha and beta)|alpha]]-axial glycosidic bond <cite>Nerinckx2005</cite>. When dividing [[Sub-site nomenclature|subsite -1]] into half-spaces by a plane defined by the glycosidic oxygen and C1' and H1' of the –1 glycoside, many ligand-complexed structures reveal that the [[General_acid/base|proton donor]] is positioned either in the ''syn'' half-space (near the ring-oxygen of the –1 glycoside), or in the ''anti'' half-space (on the opposite side of the ring-oxygen). Members of the same GH [[Families|family]] appear to share a common ''syn'' or ''anti'' [[General_acid/base|protonator]] arrangement and further, this specificity appears to be preserved within [[Clans|Clans]] of [[Families|families]]. This page's compilation of [[Sub-site nomenclature|subsite -1]] occupied complexes shows that about 70% of all GH [[Families|families]] are ''anti'' [[General_acid/base|protonators]].

Closer inspection of crystal structures of [[Sub-site nomenclature|–1/+1 subsite]]-spanning substrates, or substrate-analogue ligands, in complex with enzymes reveals a further intriguing corollary <cite>Nerinckx2005 Wu2012</cite>. In substrate-bound complexes with ''anti'' [[General_acid/base|protonating]] GH enzymes, the scissile [[Anomeric centre (alpha and beta)|anomeric bond]] (often studied using the thio-analogue) shows a dihedral angle φ (O5'-C1'-[O,S]x-Cx) that is in the lowest-energy synclinal (gauche) conformation. The rationale for this is that a minus synclinal dihedral angle φ for an equatorial glycosidic bond, or plus synclinal for an axial glycosidic bond <cite>Perez1978</cite>, allows for hyperconjugative overlap of the C1'-O5' antibonding orbital with an antiperiplanar-oriented lone pair orbital lobe of the glycosidic oxygen, thereby creating partial double bond character and stabilization of the glycosidic bond by 4–5 kcal/mol; this ground-state stabilizing phenomenon is known as the ‘exo-anomeric effect’ <cite>Cramer1997 Johnson2009 Alonso2016</cite>. ''Anti'' [[General_acid/base|protonation]] occurs on the glycosidic oxygen’s antiperiplanar lone pair, thereby removing the stabilizing exo-anomeric effect. This suggests that ''anti'' [[General_acid/base|protonation]] is an enzymic approach for lowering the activation barrier leading to the [[Transition state|transition state]] (Figure 1 centre).

''Syn'' [[General_acid/base|protonating]] [[glycoside hydrolase]]s apparently make use of a different approach <cite>Nerinckx2005 Wu2012</cite>. In many [[Sub-site nomenclature|–1/+1 subsite]]-spanning ligand complexes, the dihedral angle φ of the scissile anomeric bond has been rotated away from its lowest-energy synclinal position: clockwise to minus-anticlinal or antiperiplanar for beta-equatorial; counterclockwise to plus-anticlinal or antiperiplanar for alpha-axial [[Anomeric centre (alpha and beta)|anomeric bonds]]. This removes the hyperconjugative overlap and thus also the stabilizing exo-anomeric effect. And because of this rotation, a lone pair of the glycosidic oxygen is directed into the ''syn'' half-space, allowing it to be protonated by the ''syn''-positioned [[General_acid/base|proton donor]] (Figure 1 right).

[[File:Syn_anti.jpg|800px|thumb|center|Figure 1. Newman projections, with the glycosidic oxygen as proximal atom and the anomeric carbon as distal atom, showing ''anti'' (centre) versus ''syn'' (right) semi-lateral [[General_acid/base|protonation]] in beta-equatorial (top) and alpha-axial (bottom) [[glycoside hydrolase]]s. The indicated φ is the dihedral angle for O5'-C1'-O4-C4.]]

== Table of ''syn/anti'' protonation examples ==

This table contains only one example per GH [[Families|family]] of a ligand-complexed protein structure where the ''syn'' or ''anti'' positioning of the [[General_acid/base|proton donor]] can be clearly observed; other examples may be available on a [[Families|family-by-family]] basis. The reader is thus advised to consult the [http://www.cazy.org/fam/acc_GH.html#table CAZy database] for a current, comprehensive list of CAZyme structures. Where available, the selected examples are Michaelis-type complexes with the ligand spanning the [[Sub-site nomenclature|-1/+1 subsites]], since these have an intact glycosidic or thioglycosidic bond, or are ''N''-analogs of the substrate (''e.g.'' acarbose). In some examples, the [[General_acid/base|proton donor]] has been mutated (''e.g.'', to the corresponding amide or to an alanine), and in those cases one may wish to look at a superposition of the given PDB example with the structure of the native enzyme. If a Michaelis-type complex is not yet available, the second and third example choices, respectively, are trapped glycosyl-enzyme [[intermediate]]s and product complexes where [[Sub-site nomenclature|subsite -1]] is occupied.

''Please also be aware that this is a large table with many data. Please contact the page Author or Responsible Curator with corrections.''

=== Table ===
This table can be re-sorted by clicking on the icons in the header (''javascript must be turned on in your browser''). To reset the page to be sorted by GH family, click the ''View'' tab at the very top of the page.

{| {{Prettytable}} class="sortable"
|- valign="top"
! '''Family'''
! '''Clan'''
! '''Structure fold '''
! '''Anomeric specificity'''
! '''Mechanism'''
! '''''Syn/anti'' protonator'''
! '''Example PDB ID'''
! '''Enzyme'''
! '''Organism'''
! '''Ligand'''
! '''General acid'''
! '''Nucleophile or General base'''
! '''Reference'''
|-
| [[GH1]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002cer pdb_00002cer]
| β-glycosidase S
| ''Sulfolobus solfataricus'' P2
| phenethyl glucoimidazole
| '''Glu206'''
| Glu387
| <cite>Gloster2006</cite>
|-
| [[GH2]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002vzu pdb_00002vzu]
| exo-β-glucosaminidase
| ''Amicolatopsis orientalis''
| PNP-β-{{Smallcaps|d}}-glucosamine
| '''Glu469'''
| Glu541
| <cite>van_Bueren2009</cite>
|-
| [[GH3]]
| none
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001iex pdb_00001iex]
| exo-1,3-1,4-glucanase
| ''Hordeum vulgare''
| thiocellobiose
| '''Glu491'''
| Asp285
| <cite>Hrmova2001</cite>
|-
| [[GH4]]
| none
| Rossmann + α6/β3 + β3/α4
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001u8x pdb_00001u8x]
| 6-P-α-glucosidase
| ''Bacillus subtilis''
| alpha-{{Smallcaps|d}}-glucose-6-phosphate
| '''Asp172'''
| not applicable
| <cite>Rajan2004</cite>
|-
| [[GH5]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001h2j pdb_00001h2j]
| endo-β-1,4-glucanase
| ''Bacillus agaradhaerens''
| 2',4'-DNP-2-F-cellobioside
| '''Glu129'''
| Glu228
| <cite>Varrot2003</cite>
|-
| [[GH6]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00001qjw pdb_00001qjw]
| cellobiohydrolase 2
| ''Hypocrea jecorina''
| (Glc)2-S-(Glc)2
| '''Asp221'''
| debated
| <cite>Zhou1999</cite>
|-
| [[GH7]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00001ovw pdb_00001ovw]
| endo-1,4-glucanase
| ''Fusarium oxysporum''
| thio-(Glc)5
| '''Glu202'''
| Glu197
| <cite>Sulzenbacher1999</cite>
|-
| [[GH8]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00001kwf pdb_00001kwf]
| endo-1,4-glucanase
| ''Clostridium thermocellum''
| cellopentaose
| '''Glu95'''
| Asp278
| <cite>Guerin2002</cite>
|-
| [[GH9]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00001rq5 pdb_00001rq5]
| cellobiohydrolase
| ''Clostridium thermocellum''
| cellotetraose
| '''Glu795'''
| Asp383
| <cite>Schubot2004</cite>
|-
| [[GH10]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002d24 pdb_00002d24]
| β-1,4-xylanase
| ''Streptomyces olivaceoviridis'' E-86
| xylopentaose
| '''Glu128'''
| Glu236
| <cite>Suzuki2009</cite>
|-
| [[GH11]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00004hk8 pdb_00004hk8]
| endo-β-1,4-xylanase
| ''Hypocrea jecorina''
| xylohexaose
| '''Glu177'''
| Glu86
| <cite>Wan2014</cite>
|-
| [[GH12]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00001w2u pdb_00001w2u]
| endoglucanase
| ''Humicola grisea''
| thiocellotetraose
| '''Glu205'''
| Glu120
| <cite>Sandgren2004</cite>
|-
| [[GH13]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001cxk pdb_00001cxk]
| β-cyclodextrin glucanotransferase
| ''Bacillus circulans''
| maltononaose
| '''Glu257'''
| Asp229
| <cite>Uitdehaag1999</cite>
|-
| [[GH14]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00001itc pdb_00001itc]
| β-amylase
| ''Bacillus cereus''
| maltopentaose
| '''Glu172'''
| Glu367
| <cite>Miyake2003</cite>
|-
| [[GH15]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00001dog pdb_00001dog]
| glucoamylase
| ''Aspergillus awamori''
| 1-deoxynojirimycin
| '''Glu179'''
| Glu400
| <cite>Harris1993</cite>
|-
| [[GH16]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00001urx pdb_00001urx]
| β-agarase A
| ''Zobellia galactanivorans''
| oligoagarose
| '''Glu152'''
| Glu147
| <cite>Allouch2004</cite>
|-
| [[GH17]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00004gzj pdb_00004gzj]
| endo-β-1,3-glucanase
| ''Solanum tuberosum''
| laminaratriose + laminarabiose
| '''Glu118'''
| Glu259
| <cite>Wojtkowiak2013</cite>
|-
| [[GH18]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001ffr pdb_00001ffr]
| chitinase A
| ''Serratia marcescens''
| (NAG)6
| '''Glu315'''
| internal
| <cite>Papanikolau2001</cite>
|-
| [[GH19]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00003wh1 pdb_00003wh1]
| chitinase
| ''Bryum coronatum''
| (GlcNAc)4
| '''Glu61'''
| Glu70
| <cite>Ohnuma2014</cite>
|-
| [[GH20]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001c7s pdb_00001c7s]
| chitobiase
| ''Serratia marcescens''
| chitobiose
| '''Glu540'''
| internal
| <cite>Prag2000</cite>
|-
| [[GH22]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00001h6m pdb_00001h6m]
| lysozyme C
| ''Gallus gallus''
| Chit-2-F-chitosyl
| '''Glu35'''
| Asp52
| <cite>Vocadlo2001</cite>
|-
| [[GH23]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00001lsp pdb_00001lsp]
| lysozyme G
| ''Cygnus atratus''
| Bulgecin A
| '''Glu73'''
| internal
| <cite>Karlsen1996</cite>
|-
| [[GH24]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_0000148l pdb_0000148l]
| lysozyme E
| Bacteriophage T4
| chitobiosyl
| '''Glu11'''
| Glu26
| <cite>Baldwin1993</cite>
|-
| [[GH26]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002vx6 pdb_00002vx6]
| exo-β-mannanase
| ''Cellvibrio japonicus'' Ueda107
| Gal1Man4
| '''Glu221'''
| Glu338
| <cite>Cartmell2008</cite>
|-
| [[GH27]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}} / beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00003lrm pdb_00003lrm]
| α-galactosidase
| ''Saccharomyces cerevisiae''
| raffinose
| '''Asp209'''
| Asp141
| <cite>Fernandez-Leiro2010</cite>
|-
| [[GH28]]
| N
| β-helix
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00002uvf pdb_00002uvf]
| exo-polygalacturonosidase
| ''Yersinia enterocolitica'' ATCC9610D
| digalacturonic acid
| '''Asp402'''
| Asp381 Asp403
| <cite>Abbott2007</cite>
|-
| [[GH29]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00003uet pdb_00003uet]
| α-1,3/4-fucosidase
| ''Bifidobacterium longum'' subsp. infantis
| lacto-''N''-fucopentaose II
| '''Glu217'''
| Asp172
| <cite>Sakurama2012</cite>
|-
| [[GH30]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002y24 pdb_00002y24]
| glucurono-xylanase
| ''Dickea chrysanthemi'' D1
| glucuronoxylan tetrasaccharide
| '''Glu163'''
| Glu253
| <cite>Urbanikova2011</cite>
|-
| [[GH31]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002qmj pdb_00002qmj]
| maltase-glucoamylase
| ''Homo sapiens''
| acarbose
| '''Asp542'''
| Asp443
| <cite>Sim2008</cite>
|-
| [[GH32]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002add pdb_00002add]
| fructan β-(2,1)-fructosidase
| ''Cichorium intybus''
| sucrose
| '''Glu201'''
| Asp22
| <cite>Verhaest2007</cite>
|-
| [[GH33]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001s0i pdb_00001s0i]
| transsialidase
| ''Trypanosoma cruzi''
| sialyllactose
| '''Asp59'''
| Tyr342 (with Glu230)
| <cite>Amaya2004</cite>
|-
| [[GH34]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00004gzw pdb_00004gzw]
| N2 neuraminidase
| ''Influenza'' A Tanzania/205/2010 H3N2
| α-{{Smallcaps|d}}-Neup5Ac-(2,3)-β-{{Smallcaps|d}}-Galp-(1,4)-β-{{Smallcaps|d}}-GlcpNAc
| '''Asp151'''
| Tyr406 (with Glu277)
| <cite>Zhu2012</cite>
|-
| [[GH35]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00003ogv pdb_00003ogv]
| β-galactosidase
| ''Hypocrea jecorina''
| 2-phenylethyl 1-thio-β-{{Smallcaps|d}}-galactopyranoside
| '''Glu200'''
| Glu298
| <cite>Maksimainen2011</cite>
|-
| [[GH36]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00004fnu pdb_00004fnu]
| β-galactosidase
| ''Geobacillus stearothermophilus''
| stachyose
| '''Asp584'''
| Asp478
| <cite>Merceron2012</cite>
|-
| [[GH37]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00002jf4 pdb_00002jf4]
| trehalase
| ''Escherichia coli''
| validoxylamine
| '''Asp312'''
| Glu496
| <cite>Gibson2007</cite>
|-
| [[GH38]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00003czn pdb_00003czn]
| Golgi α-mannosidase II
| ''Drosophila melanogaster''
| GlcNAcMan(5)GlcNAc(2)
| '''Asp341'''
| Asp204
| <cite>Shah2008</cite>
|-
| [[GH39]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002bfg pdb_00002bfg]
| β-xylosidase
| ''Geobacillus stearothermophilus''
| 2,5-dinitrophenyl-β-{{Smallcaps|d}}-xyloside
| '''Glu160'''
| Glu278
| <cite>Czjzek2005</cite>
|-
| [[GH42]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00004ucf pdb_00004ucf]
| β-galactosidase
| ''Bifidobacterium bifidum''
| {{Smallcaps|d}}-galactose
| '''Glu161'''
| Glu320
| <cite>Godoy2016</cite>
|-
| [[GH43]]
| F
| 5-fold β-propeller
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00003akh pdb_00003akh]
| exo-1,5-α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces avermitilis''
| α-1,5-arabinofuranotriose
| '''Glu196'''
| Asp220
| <cite>Fujimoto2010</cite>
|-
| [[GH44]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002eqd pdb_00002eqd]
| endoglucanase
| ''Clostridium thermocellum''
| cellooctaose
| '''Glu186'''
| Glu359
| <cite>Kitago2007</cite>
|-
| [[GH45]]
| none
| 6-stranded β-barrel
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00004eng pdb_00004eng]
| endo-1,4-glucanase
| ''Humicola insolens''
| cellohexaose
| '''Asp121'''
| Asp10
| <cite>Davies1996</cite>
|-
| [[GH46]]
| I
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00004olt pdb_00004olt]
| chitosanase
| ''Microbacterium sp.'' OU01
| hexa-glucosamine
| '''Glu25'''
| Asp43
| <cite>Lyu2014</cite>
|-
| [[GH47]]
| none
| (α/α)7
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00001x9d pdb_00001x9d]
| α-mannosidase I
| ''Homo sapiens''
| Me-2-S-(α-Man)-2-thio-α-Man
| '''Asp463'''
| Glu599
| <cite>Karaveg2005</cite>, <cite>Nerinckx2008</cite>
|-
| [[GH48]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH8''
|
|
|
|
|
|
|-
| [[GH49]]
| N
| β-helix
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH28''
|
|
|
|
|
|
|-
| [[GH50]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00004bq5 pdb_00004bq5]
| exo-β-agarase
| ''Saccharophagus degradans''
| neoagarotetraose
| '''Glu535'''
| Glu695
| <cite>Pluvinage2013</cite>
|-
| [[GH51]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001qw9 pdb_00001qw9]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Geobacillus stearothermophilus''
| PNP-{{Smallcaps|l}}-arabinofuranoside
| '''Glu175'''
| Glu294
| <cite>Hoevel2003</cite>
|-
| [[GH52]]
| O
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| '' predicted perpendicular by clan, see at GH116''
| [{{PDBlink}}pdb_00004c1p pdb_00004c1p]
| β-xylosidase
| ''Geobacillus thermoglucosidasius''
| xylobiose
| '''Asp517'''
| Glu537
| <cite>Espina2014</cite>
|-
| [[GH53]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002ccr pdb_00002ccr]
| β-1,4-galactanase
| ''Bacillus licheniformis''
| galactotriose
| '''Glu165'''
| Glu263
| <cite>Le_Nours2009</cite>
|-
| [[GH54]]
| none
| β-sandwich
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001wd4 pdb_00001wd4]
| α-{{Smallcaps|l}}-arabinofuranosidase B
| ''Aspergillus kawachii''
| {{Smallcaps|l}}-arabinofuranose
| '''Asp297'''
| Glu221
| <cite>Miyanaga2004</cite>
|-
| [[GH55]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00004tz5 pdb_00004tz5]
| exo-β-1,3-glucanase
| ''Streptomyces sp.'' SirexAA-E
| laminarihexaose
| '''Glu502'''
| unknown
| <cite>Bianchetti2015</cite>
|-
| [[GH56]]
| none
| (β/α)7
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001fcv pdb_00001fcv]
| hyaluronidase
| ''Apis mellifera''
| (hyaluron.)4
| '''Glu113'''
| internal
| <cite>Markovic-Housley2000</cite>
|-
| [[GH57]]
| T
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001k1y pdb_00001k1y]
| glucanotransferase
| ''Thermococcus litoralis''
| acarbose
| '''Asp214'''
| Glu123
| <cite>Imamura2003</cite>
|-
| [[GH59]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00004ccc pdb_00004ccc]
| β-galactocerebrosidase
| ''Mus musculus''
| PNP-β-{{Smallcaps|d}}-galactoside
| '''Glu182'''
| Glu258
| <cite>Hill2013</cite>
|-
| [[GH62]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00003wn0 pdb_00003wn0]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces coelicolor''
| β-{{Smallcaps|l}}-Arabinofuranose
| '''Glu361'''
| Asp202
| <cite>Maehara2014</cite>
|-
| [[GH63]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00005ca3 pdb_00005ca3]
| α-glucosidase
| ''Escherichia coli''
| glucose and lactose
| '''Asp501'''
| Glu727
| <cite>Miyazaki2016</cite>
|-
| [[GH65]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00004ktr pdb_00004ktr]
| 2-O-α-glucosylglycerol phosphorylase
| ''Bacillus selenitireducens''
| isofagomine
| '''Glu475'''
| phosphate
| <cite>Touhara2014</cite>
|-
| [[GH66]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00005axh pdb_00005axh]
| dextranase
| ''Thermoanaerobacter pseudethanolicus''
| isomaltohexaose
| '''Glu374'''
| Asp312
| <cite>Suzuki2016</cite>
|-
| [[GH67]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00001l8n pdb_00001l8n]
| α-glucuronidase
| ''Geobacillus stearothermophilus''
| 4-O-methyl-{{Smallcaps|d}}-glucuronic acid and xylotriose
| '''Glu286'''
| Asp364 Glu392
| <cite>Golan2004</cite>
|-
| [[GH68]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001pt2 pdb_00001pt2]
| levansucrase
| ''Bacillus subtilis''
| sucrose
| '''Glu342'''
| Asp86
| <cite>Meng2003</cite>
|-
| [[GH70]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00003aic pdb_00003aic]
| glucansucrase
| ''Streptococcus mutans''
| α-acarbose
| '''Glu515'''
| Asp477
| <cite>Ito2011</cite>
|-
| [[GH72]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002w62 pdb_00002w62]
| β-1,3-glucanotransferase
| ''Saccharomyces cerevisiae'' S288C
| laminaripentaose
| '''Glu176'''
| Glu275
| <cite>Hurtado-Gerrero2009</cite>
|-
| [[GH73]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| unknown
| '''''syn'''''
| [{{PDBlink}}pdb_00007pod pdb_00007pod]
| peptidoglycan endo-β-1,4-''N''-acetylglucosaminidase
| ''Streptococcus pneumoniae'' R6
| NAG-NAM-NAG-NAM tetrasaccharide
| '''Glu585'''
| unknown
| <cite>Martinez-Caballero2023</cite>
|-
| [[GH74]]
| none
| 7-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00002ebs pdb_00002ebs]
| cellobiohydrolase (OXG-RCBH)
| ''Geotrichum sp.'' m128
| xyloglucan heptasaccharide
| '''Asp465'''
| Asp35
| <cite>Yaoi2007</cite>
|-
| [[GH76]]
| none
| (α/α)6
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00005agd pdb_00005agd]
| endo-α-1,6-mannanase
| ''Bacillus circulans''
| α-1,6-mannopentaose
| '''Asp125'''
| Asp124
| <cite>Thompson2015</cite>
|-
| [[GH77]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002oww pdb_00002oww]
| 4-α-glucanotransferase
| ''Thermus thermofilus''
| acarbose + 4-deoxy-α-{{Smallcaps|d}}-glucose
| '''Glu340'''
| Asp293
| <cite>Barends2007</cite>
|-
| [[GH78]]
| H
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00003w5n pdb_00003w5n]
| α-{{Smallcaps|l}}-rhamnosidase
| ''Streptomyces avermitilis''
| {{Smallcaps|l}}-rhamnose
| '''Glu636'''
| Glu895
| <cite>Fujimoto2013</cite>
|-
| [[GH79]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00005e9c pdb_00005e9c]
| heparanase
| ''Homo sapiens''
| heparin tetrasaccharide
| '''Glu225'''
| Glu343
| <cite>Wu2015</cite>
|-
| [[GH80]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH24''
|
|
|
|
|
|
|-
| [[GH81]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00005t4g pdb_00005t4g]
| endo-β-1,3-glucanase
| ''Bacillus halodurans'' C-125
| laminarin
| '''Asp466'''
| Glu542
| <cite>Pluvinage2017</cite>
|-
| [[GH83]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00001z4x pdb_00001z4x]
| hemagglutinin-neuraminidase
| Simian virus 5
| α-2,3-sialyllactose
| '''Asp187''' on flexible loop
| Tyr523 (with Glu390)
| <cite>Yuan2005</cite>
|-
| [[GH84]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002chn pdb_00002chn]
| β-''N''-acetyl-glucosaminidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| NAG-thiazoline
| '''Glu242'''
| internal
| <cite>Dennis2006</cite>
|-
| [[GH85]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002w92 pdb_00002w92]
| endo-β-''N''-acetyl-glucosaminidase D
| ''Streptococcus pneumoniae'' TIGR4
| NAG-thiazoline
| '''Glu337'''
| internal
| <cite>Abbott2009</cite>
|-
| [[GH86]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00004aw7 pdb_00004aw7]
| β-porphyranase
| ''Bacteroides plebeius''
| porphyran fragment
| '''Glu152'''
| Glu279
| <cite>Hehemann_1_2012</cite>
|-
| [[GH89]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00002vcb pdb_00002vcb]
| α-''N''-acetyl-glucosaminidase
| ''Clostridium perfringens''
| PUGNAc
| '''Glu483'''
| Glu601
| <cite>Ficko-Blean2008</cite>
|-
| [[GH92]]
| none
| (α/α)6 and β-sandwich
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00002ww1 pdb_00002ww1]
| α-1,2-mannosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| thiomannobioside
| '''Glu533'''
| Asp644 Asp642
| <cite>Zhu2009</cite>
|-
| [[GH93]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00003a72 pdb_00003a72]
| exo-arabinanase
| ''Penicillium chrysogenum''
| arabinobiose
| '''Glu246'''
| Glu174
| <cite>Sogabe2011</cite>
|-
| [[GH94]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00004zli pdb_00004zli]
| cellobionic acid phosphorylase
| ''Saccharophagus degradans''
| 3-O-β-{{Smallcaps|d}}-glucopyranosyl-α-{{Smallcaps|d}}-glucopyranuronic acid
| '''Asp472'''
| phosphate
| <cite>Nam2015</cite>
|-
| [[GH95]]
| none
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00002ead pdb_00002ead]
| α-1,2-{{Smallcaps|l}}-fucosidase
| ''Bifidobacterium bifidum''
| Fuc-α-1,2-Gal
| '''Glu566'''
| Asn423 Asp766
| <cite>Nagae2007</cite>
|-
| [[GH97]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining + inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00002zq0 pdb_00002zq0]
| α-glucosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| acarbose
| '''Glu532'''
| Glu508
| <cite>Kitamura2008</cite>
|-
| [[GH98]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00002wmg pdb_00002wmg]
| endo-β-1,4-galactosidase
| ''Streptococcus pneumoniae''
| A-LewisY pentasaccharide
| '''Glu158'''
| Asp251 Glu301
| <cite>Higgins2009</cite>
|-
| [[GH99]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00004ad4 pdb_00004ad4]
| endo-α-mannosidase
| ''Bacteroides xylanisolvens''
| glucose-1,3-isofagomine and α-1,2- mannobiose
| '''Glu336'''
| debated
| <cite>Thompson2012</cite>
|-
| [[GH100]]
| G
| (α/α)6 core
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00005gop pdb_00005gop]
| invertase
| ''Anabaena (Nostoc) sp.'' pcc7120
| sucrose
| '''Asp188'''
| Glu414
| <cite>Xie2016</cite>
|-
| [[GH101]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00005a56 pdb_00005a56]
| endo-α-N-acetylgalactosaminidase
| ''Streptococcus pneumoniae'' TIGR4
| β-{{Smallcaps|d}}-Galp-(1-3)-α-{{Smallcaps|d}}-GalpNAc-(1)-methyl
| '''Glu796''' +water
| Asp764
| <cite>Gregg2015</cite>
|-
| [[GH102]]
| none
| double-ψ β-barrel
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00002pi8 pdb_00002pi8]
| lytic transglycosylase A
| ''Escherichia coli''
| chitohexaose
| '''Asp308'''
| none
| <cite>van_Straaten2007</cite>
|-
| [[GH103]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00001d0k pdb_00001d0k]
| lytic transglycosylase SLT35
| ''Escherichia coli''
| murodipeptides
| '''Glu162'''
| internal
| <cite>van_Asselt2000</cite>
|-
| [[GH106]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00005mwk pdb_00005mwk]
| α-{{Smallcaps|l}}-rhamnosidase BT_0986
| ''Bacteroides thetaiotaomicron''
| pectin heptasaccharide
| '''Glu461'''
| Glu593 or Glu561
| <cite>Ndeh2017</cite>
|-
| [[GH107]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| ''predicted syn by clan''
| ''see at GH29''
|
|
|
|
|
|
|-
| [[GH110]]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00007jwf pdb_00007jwf]
| α-1,3-galactosidase
| ''Pseudoalteromonas distincta''
| Gal-α1,3-Gal
| '''Asp344'''
| Asp321 Asp345
| <cite>McGuire2020</cite>
|-
| [[GH113]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00004cd8 pdb_00004cd8]
| β-mannanase
| ''Alicyclobacillus acidocaldarius''
| mannobioimidazole
| '''Glu151'''
| Glu231
| <cite>Williams2014</cite>
|-
| [[GH116]]
| O
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''perpendicular''''' (anomaly)
| [{{PDBlink}}pdb_00008i5u pdb_00008i5u]
| β-glucosidase
| ''Thermoanaerobacterium xylanolyticum'' LX-11
| laminaribiose
| '''Asp593'''
| Glu441
| <cite>Pengthaisong2023</cite>
|-
| [[GH117]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00004ak7 pdb_00004ak7]
| α-1,3-3,6-anhydro-{{Smallcaps|l}}-galactosidase
| ''Bacteroides plebeius''
| neoagarobiose
| '''His302''' (relay from Asp320)
| Asp90
| <cite>Hehemann_2_2012</cite>
|-
| [[GH119]]
| T
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at GH57''
|
|
|
|
|
|
|-
| [[GH120]]
| none
| parallel β-helix and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00003vsv pdb_00003vsv]
| β-xylosidase XylC
| ''Thermoanaerobacterium saccharolyticum'' JW/SL-YS485
| {{Smallcaps|d}}-xylose
| '''Glu405'''
| Asp382
| <cite>Huang2012</cite>
|-
| [[GH123]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00005fr0 pdb_00005fr0]
| exo-β-N-acetyl-galactosaminidase
| ''Clostridium perfringens''
| ''N''-difluoroacetyl-{{Smallcaps|d}}-galactosamine
| '''Glu345'''
| internal
| <cite>Noach2016</cite>
|-
| [[GH124]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00006g1i pdb_00006g1i]
| endo-β-1,4-glucanase
| ''Acetivibrio thermocellus'' ATCC 27405
| fructosylated cellopentaose
| '''Glu203'''
| unknown
| <cite>Urresti2018</cite>
|-
| [[GH125]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00005m7y pdb_00005m7y]
| exo-α-1,6-mannosidase
| ''Clostridium perfringens''
| 1,6-α-mannotriose
| '''Asp220'''
| Glu393
| <cite>Alonso-Gil2016</cite>
|-
| [[GH127]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00003wrg pdb_00003wrg]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bifidobacterium longum''
| {{Smallcaps|l}}-arabinose
| '''Glu322'''
| Cys417
| <cite>Huang2014</cite>
|-
| [[GH128]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00006ufl pdb_00006ufl]
| β-1,3-glucanase
| ''Amycolatopsis mediterranei''
| laminarihexaose
| '''Glu102'''
| Glu199
| <cite>Santos2020</cite>
|-
| [[GH129]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00005wzn pdb_00005wzn]
| exo-α-''N''-acetylgalactosaminidase (NagBb)
| ''Bifidobacterium bifidum'' JCM 1254
| GalNAc
| '''Glu478'''
| Asp435
| <cite>Sato2017</cite>
|-
| [[GH130]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00005b0s pdb_00005b0s]
| β-1,2-mannobiose phosphorylase
| ''Listeria innocua''
| β-1,2-mannotriose
| '''Asp141''' relay
| phosphate
| <cite>Tsuda2015</cite>
|-
| [[GH133]]
| none
| (α/α)6
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00005d0f pdb_00005d0f]
| glycogen-debranching enzyme
| ''Nakaseomyces glabratus'' CBS 138
| maltopentaose
| '''Glu564'''
| Asp535
| <cite>Zhai2016</cite>
|-
| [[GH134]]
| none
| β + α
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00005jug pdb_00005jug]
| β-mannanase
| ''Streptomyces sp.''
| mannopentaose
| '''Glu45'''
| Asp57
| <cite>Jin2016</cite>
|-
| [[GH136]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00005gqf pdb_00005gqf]
| lacto-N-biosidase
| ''Bifidobacterium longum''
| lacto-N-biose
| '''Asp411'''
| Asp418
| <cite>Yamada2017</cite>
|-
| [[GH137]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|l}}
| unknown
| '''''anti'''''
| [{{PDBlink}}pdb_00005mui pdb_00005mui]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0996
| ''Bacteroides thetaiotaomicron''
| pectin oligosaccharide
| '''Glu240'''
| Glu159
| <cite>Ndeh2017</cite>
|-
| [[GH138]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00006hzg pdb_00006hzg]
| α-1,2-{{Smallcaps|d}}-galacturonidase
| ''Bacteroides paurosaccharolyticus''
| alpha-{{Smallcaps|d}}-galactopyranuronic
| '''Glu294'''
| Glu361
| <cite>Labourel2019</cite>
|-
| [[GH140]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH144]]
| S
| (α/α)8
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00008xul pdb_00008xul]
| beta-1,2-glucanase
| ''Xanthomonas campestris''
| beta-1,2-glucoheptasaccharide
| '''Glu239'''
| unknown
| <cite>Nakajima2024</cite>
|-
| [[GH146]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00005opj pdb_00005opj]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bacteroides thetaiotaomicron''
| {{Smallcaps|l}}-arabinose
| '''Glu320'''
| Cys416
| <cite>Luis2018</cite>
|-
| [[GH147]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH148]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH149]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH156]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00006s0e pdb_00006s0e]
| exo-α-sialidase
| uncultured bacterium pG7
| N-acetyl-2,3-dehydro-2-deoxyneuraminic acid
| '''His134''' (relay from Asp132)
| Asp14
| <cite>Bule2019</cite>
|-
| [[GH157]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH158]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH161]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH162]]
| S
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00006imw pdb_00006imw]
| endo-β-1,2-glucanase
| ''Talaromyces funiculosus''
| beta-1,2-glucan
| '''Glu262''' via C3-OH of glc at subs. +2
| Asp446
| <cite>Tanaka2019</cite>
|-
| [[GH164]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00006t75 pdb_00006t75]
| β-mannosidase
| ''Bacteroides salyersiae''
| 2-deoxy-2-F-mannosyl
| '''Glu160'''
| Glu297
| <cite>Armstrong2020</cite>
|-
| [[GH167]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|-
| [[GH168]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| '''''syn'''''
| [{{PDBlink}}pdb_00008ya7 pdb_00008ya7]
| endo-α-1,3-{{Smallcaps|l}}-fucanase (Fun168A)
| ''Wenyingzhuangia fucanilytica'' CZ1127
| sulfated fucotetraose
| '''Glu264'''
| Asp206
| <cite>Chen2024</cite>
|-
| [[GH169]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH172]]
| none
| β-jelly roll
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00007v1w pdb_00007v1w]
| difructose-anhydride synthase
| ''Bifidobacterium dentum''
| beta-{{Smallcaps|d}}-arabinofuranose
| '''Glu270'''
| Glu291
| <cite>Kashima2021</cite>
|-
| [[GH173]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH178]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at e.g. GH15''
|
|
|
|
|
|-
| [[GH181]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00008axi pdb_00008axi]
| exo-α-sialidase
| ''Akkermansia muciniphila''
| 2-deoxy-2,3-dehydro-''N''-acetyl-neuraminic acid + T-antigen disaccharide
| '''Asp345'''
| Glu218
| <cite>Shuoker2023</cite>
|-
| [[GH183]]
| none
| 5-bladed β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}pdb_00008ic1 pdb_00008ic1]
| endo-α-1,5-{{Smallcaps|d}}-arabinofuranosidase
| ''Microbacterium arabinogalactanolyticum'' JCM 9171
| α-{{Smallcaps|d}}-Araf-(1,5)-α-{{Smallcaps|d}}-Araf-(1,5)-α-{{Smallcaps|d}}-Araf-(1,5)-α-{{Smallcaps|d}}-Araf
| '''Asp51'''
| Asp33
| <cite>Shimokawa2023</cite>
|-
| [[GH186]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}pdb_00008ip1 pdb_00008ip1]
| β-1,2-glucanase
| ''Escherechia coli''
| β-1,2-glucan
| '''Asp388'''
| Asp300 + 3 waters
| <cite>Motouchi2023</cite>
|-
| [http://www.cazy.org/GH0.html n.c.*]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}pdb_00002vjj pdb_00002vjj]
| endo-α-N-acetylglucosaminidase
| Bacteriophage HK620
| O18A1 O-antigen hexasaccharide
| '''Asp339'''
| Glu372
| <cite>Barbirz2008</cite>
|}
<nowiki>*</nowiki> n.c.: Found among the collection of [http://www.cazy.org/GH0.html non-classified GH sequences in the CAZy Database].

== References ==

<biblio>
# HeightmanVasella1999 Heightman TD and Vasella AT. ''Recent Insights into Inhibition, Structure, and Mechanism of Configuration-Retaining Glycosidases.'' Angew Chem Int Ed. 1999 38(6):750-770. [http://www3.interscience.wiley.com/journal/55000581/abstract Article online].
# Nerinckx2005 pmid=15642336
# Wu2012 pmid=23137336
# Perez1978 Pérez S and Marchessault RH. ''The exo-anomeric effect: experimental evidence from crystal structures.'' Carbohydr res. 1978 65:114-120. [http://dx.doi.org/10.1016/S0008-6215(00)84218-4 DOI:10.1016/S0008-6215(00)84218-4]
# Cramer1997 Cramer CJ, Truhlar DG, and French AD. ''Exo-anomeric effects on energies and geometries of different conformations of glucose and related systems in the gas phase and aqueous solution.'' Carbohydr res. 1997 298:1-14. [http://dx.doi.org/10.1016/S0008-6215(96)00297-2 DOI:10.1016/S0008-6215(96)00297-2]
# Johnson2009 pmid=19733839
# Alonso2016 pmid=26889578
# Gloster2006 pmid=17002288
# van_Bueren2009 pmid=18976664
# Hrmova2001 pmid=11709165
# Rajan2004 pmid=15341727
# Varrot2003 pmid=12595701
# Zhou1999 pmid=10508787
# Sulzenbacher1999 pmid=10200171
# Urbanikova2011 pmid=21501386
# Guerin2002 pmid=11884144
# Schubot2004 pmid=14756552
# Suzuki2009 pmid=19279191
# Wan2014 pmid=24419374
# Sandgren2004 pmid=15364577
# Uitdehaag1999 pmid=10331869
# Miyake2003 pmid=12741813
# Harris1993 pmid=8431441
# Allouch2004 pmid=15062085
# Wojtkowiak2013 pmid=23275163
# Papanikolau2001 pmid=11560481
# Prag2000 pmid=10884356
# Vocadlo2001 pmid=11518970
# Karlsen1996 pmid=15299731
# Baldwin1993 pmid=8259514
# Cartmell2008 pmid=18799462
# Fernandez-Leiro2010 pmid=20592022
# Abbott2007 pmid=17397864
# Sakurama2012 pmid=22451675
# Sim2008 pmid=18036614
# Verhaest2007 pmid=17335500
# Amaya2004 pmid=15130470
# Zhu2012 pmid=23015718
# Maksimainen2011 pmid=21130883
# Merceron2012 pmid=23012371
# Gibson2007 pmid=17455176
# Shah2008 pmid=18599462
# Czjzek2005 pmid=16212978
# Godoy2016 pmid=27685756
# Fujimoto2010 pmid=20739278
# Kitago2007 pmid=17905739
# Davies1996 pmid=15299721
# Lyu2014 pmid=24766439
# Karaveg2005 pmid=15713668
# Nerinckx2008 pmid=18619586
# Pluvinage2013 pmid=23921382
# Yuan2005 pmid=15893670
# Hoevel2003 pmid=14517232
# Espina2014 pmid=24816105
# Le_Nours2009 pmid=19089956
# Miyanaga2004 pmid=15292273
# Bianchetti2015 pmid=25752603
# Markovic-Housley2000 pmid=11080624
# Imamura2003 pmid=12618437
# Hill2013 pmid=24297913
# Maehara2014 pmid=24482228
# Miyazaki2016 pmid=27688023
# Touhara2014 pmid=24828502
# Suzuki2016 pmid=26494689
# Golan2004 pmid=14573597
# Meng2003 pmid=14517548
# Ito2011 pmid=21354427
# Hurtado-Gerrero2009 pmid=19097997
# Yaoi2007 pmid=17498741
# Martinez-Caballero2023 pmid=37418323
# Thompson2015 pmid=25772148
# Barends2007 pmid=17420245
# Fujimoto2013 pmid=23486481
# Wu2015 pmid=26575439
# Pluvinage2017 pmid=28781080
# Dennis2006 pmid=16565725
# Abbott2009 pmid=19181667
# Hehemann_1_2012 pmid=23150581
# Ficko-Blean2008 pmid=18443291
# Zhu2009 pmid=20081828
# Sogabe2011 pmid=21543843
# Nam2015 pmid=26041776
# Nagae2007 pmid=17459873
# Kitamura2008 pmid=18981178
# Higgins2009 pmid=19608744
# van_Straaten2007 pmid=17502382
# van_Asselt2000 pmid=10684641
# Ndeh2017 pmid=28329766
# Labourel2019 pmid=30877196
# Nakajima2024 Nakajima M. et al. ''Extensive distribution of β-1,2-glucanases: finding of new glycoside hydrolase families of β-1,2-glucanases.'' BioRxiv preprint 2024. https://doi.org/10.1101/2024.02.06.578578
# Luis2018 pmid=29255254
# Bule2019 pmid=31645552
# Jin2016 Jin Y, Petricevic M, John A, Raich L, Jenkins H, Portela De Souza L, Cuskin F, Gilbert HJ, Rovira C, Goddard-Borger ED, Williams SJ, and Davies GJ. ''A β-Mannanase with a Lysozyme-like Fold and a Novel Molecular Catalytic Mechanism.'' ACS Cent Sci. 2016 Nov [http://dx.doi.org/10.1021/acscentsci.6b00232 DOI:10.1021/acscentsci.6b00232]
# Yamada2017 pmid=28392148
# Ohnuma2014 pmid=24582745
# Thompson2012 pmid=22219371
# Xie2016 pmid=27777307
# Gregg2015 pmid=26304114
# Williams2014 pmid=24339341
# Pengthaisong2023 pmid=37180965
# Hehemann_2_2012 pmid=22393053
# Huang2012 pmid=22992047
# Noach2016 pmid=27038508
# Urresti2018 pmid=30084399
# Alonso-Gil2016 pmid=28026180
# Huang2014 Huang CH, Zhu Z, Cheng YS, Chan HC, Ko TP, Chen CC, Wang I, Ho MR, Hsu ST, Zeng YF, Huang YN, Liu JR, Guo RT. ''Structure and Catalytic Mechanism of a Glycoside Hydrolase Family-127 β-L-Arabinofuranosidase (HypBA1).'' J Bioprocess Biotech. 2014 4:171 [http://dx.doi.org/10.4172/2155-9821.1000171 DOI:10.4172/2155-9821.1000171]
# Tsuda2015 pmid=26632508
# Zhai2016 pmid=27088557
# Barbirz2008 pmid=18547389
# Tanaka2019 pmid=30926603
# Armstrong2020 pmid=31871050
# Chen2024 pmid=38795894
# Santos2020 pmid=32451508
# Sato2017 pmid=28546425
# Kashima2021 pmid=34688653
# McGuire2020 pmid=33127644
# Shuoker2023 pmid=37005422
# Shimokawa2023 pmid=37726269
# Motouchi2023 pmid=37735577
</biblio>
[[Category:Definitions and explanations]]

Syn/anti lateral protonation

2025-04-15T12:36:52Z

Wim Nerinckx:

{{CuratorApproved}}
* [[Author]]: [[User:Wim Nerinckx|Wim Nerinckx]]
* [[Responsible Curator]]: [[User:Spencer Williams|Spencer Williams]]

----

== Overview ==

This page provides a table that summarizes the spatial positioning of the catalytic [[general acid]] residue in the active sites of [[glycoside hydrolase]]s, relative to the substrate. The table below updates those found in the seminal paper on this concept by Heightman and Vasella <cite>HeightmanVasella1999</cite>, and a following paper by Nerinckx ''et al.'' <cite>Nerinckx2005</cite>.

== Background ==

The ''"not from above, but from the side"'' concept of semi-lateral glycosidic oxygen [[General_acid/base|protonation]] by [[glycoside hydrolase]]s was introduced by Heightman and Vasella <cite>HeightmanVasella1999</cite>. It was originally only described for [[Anomeric centre (alpha and beta)|beta]]-equatorial [[glycoside hydrolase]]s, but appears to be equally applicable to enzymes acting on an [[Anomeric centre (alpha and beta)|alpha]]-axial glycosidic bond <cite>Nerinckx2005</cite>. When dividing [[Sub-site nomenclature|subsite -1]] into half-spaces by a plane defined by the glycosidic oxygen and C1' and H1' of the –1 glycoside, many ligand-complexed structures reveal that the [[General_acid/base|proton donor]] is positioned either in the ''syn'' half-space (near the ring-oxygen of the –1 glycoside), or in the ''anti'' half-space (on the opposite side of the ring-oxygen). Members of the same GH [[Families|family]] appear to share a common ''syn'' or ''anti'' [[General_acid/base|protonator]] arrangement and further, this specificity appears to be preserved within [[Clans|Clans]] of [[Families|families]]. This page's compilation of [[Sub-site nomenclature|subsite -1]] occupied complexes shows that about 70% of all GH [[Families|families]] are ''anti'' [[General_acid/base|protonators]].

Closer inspection of crystal structures of [[Sub-site nomenclature|–1/+1 subsite]]-spanning substrates, or substrate-analogue ligands, in complex with enzymes reveals a further intriguing corollary <cite>Nerinckx2005 Wu2012</cite>. In substrate-bound complexes with ''anti'' [[General_acid/base|protonating]] GH enzymes, the scissile [[Anomeric centre (alpha and beta)|anomeric bond]] (often studied using the thio-analogue) shows a dihedral angle φ (O5'-C1'-[O,S]x-Cx) that is in the lowest-energy synclinal (gauche) conformation. The rationale for this is that a minus synclinal dihedral angle φ for an equatorial glycosidic bond, or plus synclinal for an axial glycosidic bond <cite>Perez1978</cite>, allows for hyperconjugative overlap of the C1'-O5' antibonding orbital with an antiperiplanar-oriented lone pair orbital lobe of the glycosidic oxygen, thereby creating partial double bond character and stabilization of the glycosidic bond by 4–5 kcal/mol; this ground-state stabilizing phenomenon is known as the ‘exo-anomeric effect’ <cite>Cramer1997 Johnson2009 Alonso2016</cite>. ''Anti'' [[General_acid/base|protonation]] occurs on the glycosidic oxygen’s antiperiplanar lone pair, thereby removing the stabilizing exo-anomeric effect. This suggests that ''anti'' [[General_acid/base|protonation]] is an enzymic approach for lowering the activation barrier leading to the [[Transition state|transition state]] (Figure 1 centre).

''Syn'' [[General_acid/base|protonating]] [[glycoside hydrolase]]s apparently make use of a different approach <cite>Nerinckx2005 Wu2012</cite>. In many [[Sub-site nomenclature|–1/+1 subsite]]-spanning ligand complexes, the dihedral angle φ of the scissile anomeric bond has been rotated away from its lowest-energy synclinal position: clockwise to minus-anticlinal or antiperiplanar for beta-equatorial; counterclockwise to plus-anticlinal or antiperiplanar for alpha-axial [[Anomeric centre (alpha and beta)|anomeric bonds]]. This removes the hyperconjugative overlap and thus also the stabilizing exo-anomeric effect. And because of this rotation, a lone pair of the glycosidic oxygen is directed into the ''syn'' half-space, allowing it to be protonated by the ''syn''-positioned [[General_acid/base|proton donor]] (Figure 1 right).

[[File:Syn_anti.jpg|800px|thumb|center|Figure 1. Newman projections, with the glycosidic oxygen as proximal atom and the anomeric carbon as distal atom, showing ''anti'' (centre) versus ''syn'' (right) semi-lateral [[General_acid/base|protonation]] in beta-equatorial (top) and alpha-axial (bottom) [[glycoside hydrolase]]s. The indicated φ is the dihedral angle for O5'-C1'-O4-C4.]]

== Table of ''syn/anti'' protonation examples ==

This table contains only one example per GH [[Families|family]] of a ligand-complexed protein structure where the ''syn'' or ''anti'' positioning of the [[General_acid/base|proton donor]] can be clearly observed; other examples may be available on a [[Families|family-by-family]] basis. The reader is thus advised to consult the [http://www.cazy.org/fam/acc_GH.html#table CAZy database] for a current, comprehensive list of CAZyme structures. Where available, the selected examples are Michaelis-type complexes with the ligand spanning the [[Sub-site nomenclature|-1/+1 subsites]], since these have an intact glycosidic or thioglycosidic bond, or are ''N''-analogs of the substrate (''e.g.'' acarbose). In some examples, the [[General_acid/base|proton donor]] has been mutated (''e.g.'', to the corresponding amide or to an alanine), and in those cases one may wish to look at a superposition of the given PDB example with the structure of the native enzyme. If a Michaelis-type complex is not yet available, the second and third example choices, respectively, are trapped glycosyl-enzyme [[intermediate]]s and product complexes where [[Sub-site nomenclature|subsite -1]] is occupied.

''Please also be aware that this is a large table with many data. Please contact the page Author or Responsible Curator with corrections.''

=== Table ===
This table can be re-sorted by clicking on the icons in the header (''javascript must be turned on in your browser''). To reset the page to be sorted by GH family, click the ''View'' tab at the very top of the page.

{| {{Prettytable}} class="sortable"
|- valign="top"
! '''Family'''
! '''Clan'''
! '''Structure fold '''
! '''Anomeric specificity'''
! '''Mechanism'''
! '''''Syn/anti'' protonator'''
! '''Example PDB ID'''
! '''Enzyme'''
! '''Organism'''
! '''Ligand'''
! '''General acid'''
! '''Nucleophile or General base'''
! '''Reference'''
|-
| [[GH1]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2cer 2cer]
| β-glycosidase S
| ''Sulfolobus solfataricus'' P2
| phenethyl glucoimidazole
| '''Glu206'''
| Glu387
| <cite>Gloster2006</cite>
|-
| [[GH2]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vzu 2vzu]
| exo-β-glucosaminidase
| ''Amicolatopsis orientalis''
| PNP-β-{{Smallcaps|d}}-glucosamine
| '''Glu469'''
| Glu541
| <cite>van_Bueren2009</cite>
|-
| [[GH3]]
| none
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1iex 1iex]
| exo-1,3-1,4-glucanase
| ''Hordeum vulgare''
| thiocellobiose
| '''Glu491'''
| Asp285
| <cite>Hrmova2001</cite>
|-
| [[GH4]]
| none
| Rossmann + α6/β3 + β3/α4
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1u8x 1u8x]
| 6-P-α-glucosidase
| ''Bacillus subtilis''
| alpha-{{Smallcaps|d}}-glucose-6-phosphate
| '''Asp172'''
| not applicable
| <cite>Rajan2004</cite>
|-
| [[GH5]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1h2j 1h2j]
| endo-β-1,4-glucanase
| ''Bacillus agaradhaerens''
| 2',4'-DNP-2-F-cellobioside
| '''Glu129'''
| Glu228
| <cite>Varrot2003</cite>
|-
| [[GH6]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1qjw 1qjw]
| cellobiohydrolase 2
| ''Hypocrea jecorina''
| (Glc)2-S-(Glc)2
| '''Asp221'''
| debated
| <cite>Zhou1999</cite>
|-
| [[GH7]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1ovw 1ovw]
| endo-1,4-glucanase
| ''Fusarium oxysporum''
| thio-(Glc)5
| '''Glu202'''
| Glu197
| <cite>Sulzenbacher1999</cite>
|-
| [[GH8]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1kwf 1kwf]
| endo-1,4-glucanase
| ''Clostridium thermocellum''
| cellopentaose
| '''Glu95'''
| Asp278
| <cite>Guerin2002</cite>
|-
| [[GH9]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1rq5 1rq5]
| cellobiohydrolase
| ''Clostridium thermocellum''
| cellotetraose
| '''Glu795'''
| Asp383
| <cite>Schubot2004</cite>
|-
| [[GH10]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2d24 2d24]
| β-1,4-xylanase
| ''Streptomyces olivaceoviridis'' E-86
| xylopentaose
| '''Glu128'''
| Glu236
| <cite>Suzuki2009</cite>
|-
| [[GH11]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}4hk8 4hk8]
| endo-β-1,4-xylanase
| ''Hypocrea jecorina''
| xylohexaose
| '''Glu177'''
| Glu86
| <cite>Wan2014</cite>
|-
| [[GH12]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1w2u 1w2u]
| endoglucanase
| ''Humicola grisea''
| thiocellotetraose
| '''Glu205'''
| Glu120
| <cite>Sandgren2004</cite>
|-
| [[GH13]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1cxk 1cxk]
| β-cyclodextrin glucanotransferase
| ''Bacillus circulans''
| maltononaose
| '''Glu257'''
| Asp229
| <cite>Uitdehaag1999</cite>
|-
| [[GH14]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1itc 1itc]
| β-amylase
| ''Bacillus cereus''
| maltopentaose
| '''Glu172'''
| Glu367
| <cite>Miyake2003</cite>
|-
| [[GH15]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1dog 1dog]
| glucoamylase
| ''Aspergillus awamori''
| 1-deoxynojirimycin
| '''Glu179'''
| Glu400
| <cite>Harris1993</cite>
|-
| [[GH16]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1urx 1urx]
| β-agarase A
| ''Zobellia galactanivorans''
| oligoagarose
| '''Glu152'''
| Glu147
| <cite>Allouch2004</cite>
|-
| [[GH17]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzj 4gzj]
| endo-β-1,3-glucanase
| ''Solanum tuberosum''
| laminaratriose + laminarabiose
| '''Glu118'''
| Glu259
| <cite>Wojtkowiak2013</cite>
|-
| [[GH18]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1ffr 1ffr]
| chitinase A
| ''Serratia marcescens''
| (NAG)6
| '''Glu315'''
| internal
| <cite>Papanikolau2001</cite>
|-
| [[GH19]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}3wh1 3wh1]
| chitinase
| ''Bryum coronatum''
| (GlcNAc)4
| '''Glu61'''
| Glu70
| <cite>Ohnuma2014</cite>
|-
| [[GH20]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1c7s 1c7s]
| chitobiase
| ''Serratia marcescens''
| chitobiose
| '''Glu540'''
| internal
| <cite>Prag2000</cite>
|-
| [[GH22]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1h6m 1h6m]
| lysozyme C
| ''Gallus gallus''
| Chit-2-F-chitosyl
| '''Glu35'''
| Asp52
| <cite>Vocadlo2001</cite>
|-
| [[GH23]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1lsp 1lsp]
| lysozyme G
| ''Cygnus atratus''
| Bulgecin A
| '''Glu73'''
| internal
| <cite>Karlsen1996</cite>
|-
| [[GH24]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}148l 148l]
| lysozyme E
| Bacteriophage T4
| chitobiosyl
| '''Glu11'''
| Glu26
| <cite>Baldwin1993</cite>
|-
| [[GH26]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vx6 2vx6]
| exo-β-mannanase
| ''Cellvibrio japonicus'' Ueda107
| Gal1Man4
| '''Glu221'''
| Glu338
| <cite>Cartmell2008</cite>
|-
| [[GH27]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}} / beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3lrm 3lrm]
| α-galactosidase
| ''Saccharomyces cerevisiae''
| raffinose
| '''Asp209'''
| Asp141
| <cite>Fernandez-Leiro2010</cite>
|-
| [[GH28]]
| N
| β-helix
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}2uvf 2uvf]
| exo-polygalacturonosidase
| ''Yersinia enterocolitica'' ATCC9610D
| digalacturonic acid
| '''Asp402'''
| Asp381 Asp403
| <cite>Abbott2007</cite>
|-
| [[GH29]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| '''''syn'''''
| [{{PDBlink}}3uet 3uet]
| α-1,3/4-fucosidase
| ''Bifidobacterium longum'' subsp. infantis
| lacto-''N''-fucopentaose II
| '''Glu217'''
| Asp172
| <cite>Sakurama2012</cite>
|-
| [[GH30]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2y24 2y24]
| glucurono-xylanase
| ''Dickea chrysanthemi'' D1
| glucuronoxylan tetrasaccharide
| '''Glu163'''
| Glu253
| <cite>Urbanikova2011</cite>
|-
| [[GH31]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2qmj 2qmj]
| maltase-glucoamylase
| ''Homo sapiens''
| acarbose
| '''Asp542'''
| Asp443
| <cite>Sim2008</cite>
|-
| [[GH32]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2add 2add]
| fructan β-(2,1)-fructosidase
| ''Cichorium intybus''
| sucrose
| '''Glu201'''
| Asp22
| <cite>Verhaest2007</cite>
|-
| [[GH33]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1s0i 1s0i]
| transsialidase
| ''Trypanosoma cruzi''
| sialyllactose
| '''Asp59'''
| Tyr342 (with Glu230)
| <cite>Amaya2004</cite>
|-
| [[GH34]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzw 4gzw]
| N2 neuraminidase
| ''Influenza'' A Tanzania/205/2010 H3N2
| α-{{Smallcaps|d}}-Neup5Ac-(2,3)-β-{{Smallcaps|d}}-Galp-(1,4)-β-{{Smallcaps|d}}-GlcpNAc
| '''Asp151'''
| Tyr406 (with Glu277)
| <cite>Zhu2012</cite>
|-
| [[GH35]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3ogv 3ogv]
| β-galactosidase
| ''Hypocrea jecorina''
| 2-phenylethyl 1-thio-β-{{Smallcaps|d}}-galactopyranoside
| '''Glu200'''
| Glu298
| <cite>Maksimainen2011</cite>
|-
| [[GH36]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4fnu 4fnu]
| β-galactosidase
| ''Geobacillus stearothermophilus''
| stachyose
| '''Asp584'''
| Asp478
| <cite>Merceron2012</cite>
|-
| [[GH37]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2jf4 2jf4]
| trehalase
| ''Escherichia coli''
| validoxylamine
| '''Asp312'''
| Glu496
| <cite>Gibson2007</cite>
|-
| [[GH38]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3czn 3czn]
| Golgi α-mannosidase II
| ''Drosophila melanogaster''
| GlcNAcMan(5)GlcNAc(2)
| '''Asp341'''
| Asp204
| <cite>Shah2008</cite>
|-
| [[GH39]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2bfg 2bfg]
| β-xylosidase
| ''Geobacillus stearothermophilus''
| 2,5-dinitrophenyl-β-{{Smallcaps|d}}-xyloside
| '''Glu160'''
| Glu278
| <cite>Czjzek2005</cite>
|-
| [[GH42]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ucf 4ucf]
| β-galactosidase
| ''Bifidobacterium bifidum''
| {{Smallcaps|d}}-galactose
| '''Glu161'''
| Glu320
| <cite>Godoy2016</cite>
|-
| [[GH43]]
| F
| 5-fold β-propeller
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3akh 3akh]
| exo-1,5-α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces avermitilis''
| α-1,5-arabinofuranotriose
| '''Glu196'''
| Asp220
| <cite>Fujimoto2010</cite>
|-
| [[GH44]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2eqd 2eqd]
| endoglucanase
| ''Clostridium thermocellum''
| cellooctaose
| '''Glu186'''
| Glu359
| <cite>Kitago2007</cite>
|-
| [[GH45]]
| none
| 6-stranded β-barrel
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4eng 4eng]
| endo-1,4-glucanase
| ''Humicola insolens''
| cellohexaose
| '''Asp121'''
| Asp10
| <cite>Davies1996</cite>
|-
| [[GH46]]
| I
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4olt 4olt]
| chitosanase
| ''Microbacterium sp.'' OU01
| hexa-glucosamine
| '''Glu25'''
| Asp43
| <cite>Lyu2014</cite>
|-
| [[GH47]]
| none
| (α/α)7
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1x9d 1x9d]
| α-mannosidase I
| ''Homo sapiens''
| Me-2-S-(α-Man)-2-thio-α-Man
| '''Asp463'''
| Glu599
| <cite>Karaveg2005</cite>, <cite>Nerinckx2008</cite>
|-
| [[GH48]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH8''
|
|
|
|
|
|
|-
| [[GH49]]
| N
| β-helix
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH28''
|
|
|
|
|
|
|-
| [[GH50]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4bq5 4bq5]
| exo-β-agarase
| ''Saccharophagus degradans''
| neoagarotetraose
| '''Glu535'''
| Glu695
| <cite>Pluvinage2013</cite>
|-
| [[GH51]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1qw9 1qw9]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Geobacillus stearothermophilus''
| PNP-{{Smallcaps|l}}-arabinofuranoside
| '''Glu175'''
| Glu294
| <cite>Hoevel2003</cite>
|-
| [[GH52]]
| O
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| '' predicted perpendicular by clan, see at GH116''
| [{{PDBlink}}4c1p 4c1p]
| β-xylosidase
| ''Geobacillus thermoglucosidasius''
| xylobiose
| '''Asp517'''
| Glu537
| <cite>Espina2014</cite>
|-
| [[GH53]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2ccr 2ccr]
| β-1,4-galactanase
| ''Bacillus licheniformis''
| galactotriose
| '''Glu165'''
| Glu263
| <cite>Le_Nours2009</cite>
|-
| [[GH54]]
| none
| β-sandwich
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1wd4 1wd4]
| α-{{Smallcaps|l}}-arabinofuranosidase B
| ''Aspergillus kawachii''
| {{Smallcaps|l}}-arabinofuranose
| '''Asp297'''
| Glu221
| <cite>Miyanaga2004</cite>
|-
| [[GH55]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4tz5 4tz5]
| exo-β-1,3-glucanase
| ''Streptomyces sp.'' SirexAA-E
| laminarihexaose
| '''Glu502'''
| unknown
| <cite>Bianchetti2015</cite>
|-
| [[GH56]]
| none
| (β/α)7
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1fcv 1fcv]
| hyaluronidase
| ''Apis mellifera''
| (hyaluron.)4
| '''Glu113'''
| internal
| <cite>Markovic-Housley2000</cite>
|-
| [[GH57]]
| T
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1k1y 1k1y]
| glucanotransferase
| ''Thermococcus litoralis''
| acarbose
| '''Asp214'''
| Glu123
| <cite>Imamura2003</cite>
|-
| [[GH59]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ccc 4ccc]
| β-galactocerebrosidase
| ''Mus musculus''
| PNP-β-{{Smallcaps|d}}-galactoside
| '''Glu182'''
| Glu258
| <cite>Hill2013</cite>
|-
| [[GH62]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3wn0 3wn0]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces coelicolor''
| β-{{Smallcaps|l}}-Arabinofuranose
| '''Glu361'''
| Asp202
| <cite>Maehara2014</cite>
|-
| [[GH63]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5ca3 5ca3]
| α-glucosidase
| ''Escherichia coli''
| glucose and lactose
| '''Asp501'''
| Glu727
| <cite>Miyazaki2016</cite>
|-
| [[GH65]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}4ktr 4ktr]
| 2-O-α-glucosylglycerol phosphorylase
| ''Bacillus selenitireducens''
| isofagomine
| '''Glu475'''
| phosphate
| <cite>Touhara2014</cite>
|-
| [[GH66]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5axh 5axh]
| dextranase
| ''Thermoanaerobacter pseudethanolicus''
| isomaltohexaose
| '''Glu374'''
| Asp312
| <cite>Suzuki2016</cite>
|-
| [[GH67]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1l8n 1l8n]
| α-glucuronidase
| ''Geobacillus stearothermophilus''
| 4-O-methyl-{{Smallcaps|d}}-glucuronic acid and xylotriose
| '''Glu286'''
| Asp364 Glu392
| <cite>Golan2004</cite>
|-
| [[GH68]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1pt2 1pt2]
| levansucrase
| ''Bacillus subtilis''
| sucrose
| '''Glu342'''
| Asp86
| <cite>Meng2003</cite>
|-
| [[GH70]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3aic 3aic]
| glucansucrase
| ''Streptococcus mutans''
| α-acarbose
| '''Glu515'''
| Asp477
| <cite>Ito2011</cite>
|-
| [[GH72]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w62 2w62]
| β-1,3-glucanotransferase
| ''Saccharomyces cerevisiae'' S288C
| laminaripentaose
| '''Glu176'''
| Glu275
| <cite>Hurtado-Gerrero2009</cite>
|-
| [[GH73]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| unknown
| '''''syn'''''
| [{{PDBlink}}7pod 7pod]
| peptidoglycan endo-β-1,4-''N''-acetylglucosaminidase
| ''Streptococcus pneumoniae'' R6
| NAG-NAM-NAG-NAM tetrasaccharide
| '''Glu585'''
| unknown
| <cite>Martinez-Caballero2023</cite>
|-
| [[GH74]]
| none
| 7-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}2ebs 2ebs]
| cellobiohydrolase (OXG-RCBH)
| ''Geotrichum sp.'' m128
| xyloglucan heptasaccharide
| '''Asp465'''
| Asp35
| <cite>Yaoi2007</cite>
|-
| [[GH76]]
| none
| (α/α)6
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5agd 5agd]
| endo-α-1,6-mannanase
| ''Bacillus circulans''
| α-1,6-mannopentaose
| '''Asp125'''
| Asp124
| <cite>Thompson2015</cite>
|-
| [[GH77]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2oww 2oww]
| 4-α-glucanotransferase
| ''Thermus thermofilus''
| acarbose + 4-deoxy-α-{{Smallcaps|d}}-glucose
| '''Glu340'''
| Asp293
| <cite>Barends2007</cite>
|-
| [[GH78]]
| H
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3w5n 3w5n]
| α-{{Smallcaps|l}}-rhamnosidase
| ''Streptomyces avermitilis''
| {{Smallcaps|l}}-rhamnose
| '''Glu636'''
| Glu895
| <cite>Fujimoto2013</cite>
|-
| [[GH79]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5e9c 5e9c]
| heparanase
| ''Homo sapiens''
| heparin tetrasaccharide
| '''Glu225'''
| Glu343
| <cite>Wu2015</cite>
|-
| [[GH80]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH24''
|
|
|
|
|
|
|-
| [[GH81]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5t4g 5t4g]
| endo-β-1,3-glucanase
| ''Bacillus halodurans'' C-125
| laminarin
| '''Asp466'''
| Glu542
| <cite>Pluvinage2017</cite>
|-
| [[GH83]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1z4x 1z4x]
| hemagglutinin-neuraminidase
| Simian virus 5
| α-2,3-sialyllactose
| '''Asp187''' on flexible loop
| Tyr523 (with Glu390)
| <cite>Yuan2005</cite>
|-
| [[GH84]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2chn 2chn]
| β-''N''-acetyl-glucosaminidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| NAG-thiazoline
| '''Glu242'''
| internal
| <cite>Dennis2006</cite>
|-
| [[GH85]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w92 2w92]
| endo-β-''N''-acetyl-glucosaminidase D
| ''Streptococcus pneumoniae'' TIGR4
| NAG-thiazoline
| '''Glu337'''
| internal
| <cite>Abbott2009</cite>
|-
| [[GH86]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4aw7 4aw7]
| β-porphyranase
| ''Bacteroides plebeius''
| porphyran fragment
| '''Glu152'''
| Glu279
| <cite>Hehemann_1_2012</cite>
|-
| [[GH89]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vcb 2vcb]
| α-''N''-acetyl-glucosaminidase
| ''Clostridium perfringens''
| PUGNAc
| '''Glu483'''
| Glu601
| <cite>Ficko-Blean2008</cite>
|-
| [[GH92]]
| none
| (α/α)6 and β-sandwich
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ww1 2ww1]
| α-1,2-mannosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| thiomannobioside
| '''Glu533'''
| Asp644 Asp642
| <cite>Zhu2009</cite>
|-
| [[GH93]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3a72 3a72]
| exo-arabinanase
| ''Penicillium chrysogenum''
| arabinobiose
| '''Glu246'''
| Glu174
| <cite>Sogabe2011</cite>
|-
| [[GH94]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4zli 4zli]
| cellobionic acid phosphorylase
| ''Saccharophagus degradans''
| 3-O-β-{{Smallcaps|d}}-glucopyranosyl-α-{{Smallcaps|d}}-glucopyranuronic acid
| '''Asp472'''
| phosphate
| <cite>Nam2015</cite>
|-
| [[GH95]]
| none
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ead 2ead]
| α-1,2-{{Smallcaps|l}}-fucosidase
| ''Bifidobacterium bifidum''
| Fuc-α-1,2-Gal
| '''Glu566'''
| Asn423 Asp766
| <cite>Nagae2007</cite>
|-
| [[GH97]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining + inverting
| '''''anti'''''
| [{{PDBlink}}2zq0 2zq0]
| α-glucosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| acarbose
| '''Glu532'''
| Glu508
| <cite>Kitamura2008</cite>
|-
| [[GH98]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2wmg 2wmg]
| endo-β-1,4-galactosidase
| ''Streptococcus pneumoniae''
| A-LewisY pentasaccharide
| '''Glu158'''
| Asp251 Glu301
| <cite>Higgins2009</cite>
|-
| [[GH99]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ad4 4ad4]
| endo-α-mannosidase
| ''Bacteroides xylanisolvens''
| glucose-1,3-isofagomine and α-1,2- mannobiose
| '''Glu336'''
| debated
| <cite>Thompson2012</cite>
|-
| [[GH100]]
| G
| (α/α)6 core
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5gop 5gop]
| invertase
| ''Anabaena (Nostoc) sp.'' pcc7120
| sucrose
| '''Asp188'''
| Glu414
| <cite>Xie2016</cite>
|-
| [[GH101]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5a56 5a56]
| endo-α-N-acetylgalactosaminidase
| ''Streptococcus pneumoniae'' TIGR4
| β-{{Smallcaps|d}}-Galp-(1-3)-α-{{Smallcaps|d}}-GalpNAc-(1)-methyl
| '''Glu796''' +water
| Asp764
| <cite>Gregg2015</cite>
|-
| [[GH102]]
| none
| double-ψ β-barrel
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}2pi8 2pi8]
| lytic transglycosylase A
| ''Escherichia coli''
| chitohexaose
| '''Asp308'''
| none
| <cite>van_Straaten2007</cite>
|-
| [[GH103]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1d0k 1d0k]
| lytic transglycosylase SLT35
| ''Escherichia coli''
| murodipeptides
| '''Glu162'''
| internal
| <cite>van_Asselt2000</cite>
|-
| [[GH106]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5mwk 5mwk]
| α-{{Smallcaps|l}}-rhamnosidase BT_0986
| ''Bacteroides thetaiotaomicron''
| pectin heptasaccharide
| '''Glu461'''
| Glu593 or Glu561
| <cite>Ndeh2017</cite>
|-
| [[GH107]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| ''predicted syn by clan''
| ''see at GH29''
|
|
|
|
|
|
|-
| [[GH110]]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}7jwf 7jwf]
| α-1,3-galactosidase
| ''Pseudoalteromonas distincta''
| Gal-α1,3-Gal
| '''Asp344'''
| Asp321 Asp345
| <cite>McGuire2020</cite>
|-
| [[GH113]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4cd8 4cd8]
| β-mannanase
| ''Alicyclobacillus acidocaldarius''
| mannobioimidazole
| '''Glu151'''
| Glu231
| <cite>Williams2014</cite>
|-
| [[GH116]]
| O
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''perpendicular''''' (anomaly)
| [{{PDBlink}}8i5u 8i5u]
| β-glucosidase
| ''Thermoanaerobacterium xylanolyticum'' LX-11
| laminaribiose
| '''Asp593'''
| Glu441
| <cite>Pengthaisong2023</cite>
|-
| [[GH117]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}4ak7 4ak7]
| α-1,3-3,6-anhydro-{{Smallcaps|l}}-galactosidase
| ''Bacteroides plebeius''
| neoagarobiose
| '''His302''' (relay from Asp320)
| Asp90
| <cite>Hehemann_2_2012</cite>
|-
| [[GH119]]
| T
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at GH57''
|
|
|
|
|
|
|-
| [[GH120]]
| none
| parallel β-helix and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3vsv 3vsv]
| β-xylosidase XylC
| ''Thermoanaerobacterium saccharolyticum'' JW/SL-YS485
| {{Smallcaps|d}}-xylose
| '''Glu405'''
| Asp382
| <cite>Huang2012</cite>
|-
| [[GH123]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5fr0 5fr0]
| exo-β-N-acetyl-galactosaminidase
| ''Clostridium perfringens''
| ''N''-difluoroacetyl-{{Smallcaps|d}}-galactosamine
| '''Glu345'''
| internal
| <cite>Noach2016</cite>
|-
| [[GH124]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}6g1i 6g1i]
| endo-β-1,4-glucanase
| ''Acetivibrio thermocellus'' ATCC 27405
| fructosylated cellopentaose
| '''Glu203'''
| unknown
| <cite>Urresti2018</cite>
|-
| [[GH125]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5m7y 5m7y]
| exo-α-1,6-mannosidase
| ''Clostridium perfringens''
| 1,6-α-mannotriose
| '''Asp220'''
| Glu393
| <cite>Alonso-Gil2016</cite>
|-
| [[GH127]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3wrg 3wrg]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bifidobacterium longum''
| {{Smallcaps|l}}-arabinose
| '''Glu322'''
| Cys417
| <cite>Huang2014</cite>
|-
| [[GH128]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}6ufl 6ufl]
| β-1,3-glucanase
| ''Amycolatopsis mediterranei''
| laminarihexaose
| '''Glu102'''
| Glu199
| <cite>Santos2020</cite>
|-
| [[GH129]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5wzn 5wzn]
| exo-α-''N''-acetylgalactosaminidase (NagBb)
| ''Bifidobacterium bifidum'' JCM 1254
| GalNAc
| '''Glu478'''
| Asp435
| <cite>Sato2017</cite>
|-
| [[GH130]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5b0s 5b0s]
| β-1,2-mannobiose phosphorylase
| ''Listeria innocua''
| β-1,2-mannotriose
| '''Asp141''' relay
| phosphate
| <cite>Tsuda2015</cite>
|-
| [[GH133]]
| none
| (α/α)6
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5d0f 5d0f]
| glycogen-debranching enzyme
| ''Nakaseomyces glabratus'' CBS 138
| maltopentaose
| '''Glu564'''
| Asp535
| <cite>Zhai2016</cite>
|-
| [[GH134]]
| none
| β + α
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5jug 5jug]
| β-mannanase
| ''Streptomyces sp.''
| mannopentaose
| '''Glu45'''
| Asp57
| <cite>Jin2016</cite>
|-
| [[GH136]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}5gqf 5gqf]
| lacto-N-biosidase
| ''Bifidobacterium longum''
| lacto-N-biose
| '''Asp411'''
| Asp418
| <cite>Yamada2017</cite>
|-
| [[GH137]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|l}}
| unknown
| '''''anti'''''
| [{{PDBlink}}5mui 5mui]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0996
| ''Bacteroides thetaiotaomicron''
| pectin oligosaccharide
| '''Glu240'''
| Glu159
| <cite>Ndeh2017</cite>
|-
| [[GH138]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}6hzg 6hzg]
| α-1,2-{{Smallcaps|d}}-galacturonidase
| ''Bacteroides paurosaccharolyticus''
| alpha-{{Smallcaps|d}}-galactopyranuronic
| '''Glu294'''
| Glu361
| <cite>Labourel2019</cite>
|-
| [[GH140]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH144]]
| S
| (α/α)8
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}8xul 8xul]
| beta-1,2-glucanase
| ''Xanthomonas campestris''
| beta-1,2-glucoheptasaccharide
| '''Glu239'''
| unknown
| <cite>Nakajima2024</cite>
|-
| [[GH146]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5opj 5opj]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bacteroides thetaiotaomicron''
| {{Smallcaps|l}}-arabinose
| '''Glu320'''
| Cys416
| <cite>Luis2018</cite>
|-
| [[GH147]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH148]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH149]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH156]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}6s0e 6s0e]
| exo-α-sialidase
| uncultured bacterium pG7
| N-acetyl-2,3-dehydro-2-deoxyneuraminic acid
| '''His134''' (relay from Asp132)
| Asp14
| <cite>Bule2019</cite>
|-
| [[GH157]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH158]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH161]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH162]]
| S
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}6imw 6imw]
| endo-β-1,2-glucanase
| ''Talaromyces funiculosus''
| beta-1,2-glucan
| '''Glu262''' via C3-OH of glc at subs. +2
| Asp446
| <cite>Tanaka2019</cite>
|-
| [[GH164]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}6t75 6t75]
| β-mannosidase
| ''Bacteroides salyersiae''
| 2-deoxy-2-F-mannosyl
| '''Glu160'''
| Glu297
| <cite>Armstrong2020</cite>
|-
| [[GH167]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|-
| [[GH168]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| '''''syn'''''
| [{{PDBlink}}8ya7 8ya7]
| endo-α-1,3-{{Smallcaps|l}}-fucanase (Fun168A)
| ''Wenyingzhuangia fucanilytica'' CZ1127
| sulfated fucotetraose
| '''Glu264'''
| Asp206
| <cite>Chen2024</cite>
|-
| [[GH169]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH172]]
| none
| β-jelly roll
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}7v1w 7v1w]
| difructose-anhydride synthase
| ''Bifidobacterium dentum''
| beta-{{Smallcaps|d}}-arabinofuranose
| '''Glu270'''
| Glu291
| <cite>Kashima2021</cite>
|-
| [[GH173]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH178]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at e.g. GH15''
|
|
|
|
|
|-
| [[GH181]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}8axi 8axi]
| exo-α-sialidase
| ''Akkermansia muciniphila''
| 2-deoxy-2,3-dehydro-''N''-acetyl-neuraminic acid + T-antigen disaccharide
| '''Asp345'''
| Glu218
| <cite>Shuoker2023</cite>
|-
| [[GH183]]
| none
| 5-bladed β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}8ic1 8ic1]
| endo-α-1,5-{{Smallcaps|d}}-arabinofuranosidase
| ''Microbacterium arabinogalactanolyticum'' JCM 9171
| α-{{Smallcaps|d}}-Araf-(1,5)-α-{{Smallcaps|d}}-Araf-(1,5)-α-{{Smallcaps|d}}-Araf-(1,5)-α-{{Smallcaps|d}}-Araf
| '''Asp51'''
| Asp33
| <cite>Shimokawa2023</cite>
|-
| [[GH186]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}8ip1 8ip1]
| β-1,2-glucanase
| ''Escherechia coli''
| β-1,2-glucan
| '''Asp388'''
| Asp300 + 3 waters
| <cite>Motouchi2023</cite>
|-
| [http://www.cazy.org/GH0.html n.c.*]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2vjj 2vjj]
| endo-α-N-acetylglucosaminidase
| Bacteriophage HK620
| O18A1 O-antigen hexasaccharide
| '''Asp339'''
| Glu372
| <cite>Barbirz2008</cite>
|}
<nowiki>*</nowiki> n.c.: Found among the collection of [http://www.cazy.org/GH0.html non-classified GH sequences in the CAZy Database].

== References ==

<biblio>
# HeightmanVasella1999 Heightman TD and Vasella AT. ''Recent Insights into Inhibition, Structure, and Mechanism of Configuration-Retaining Glycosidases.'' Angew Chem Int Ed. 1999 38(6):750-770. [http://www3.interscience.wiley.com/journal/55000581/abstract Article online].
# Nerinckx2005 pmid=15642336
# Wu2012 pmid=23137336
# Perez1978 Pérez S and Marchessault RH. ''The exo-anomeric effect: experimental evidence from crystal structures.'' Carbohydr res. 1978 65:114-120. [http://dx.doi.org/10.1016/S0008-6215(00)84218-4 DOI:10.1016/S0008-6215(00)84218-4]
# Cramer1997 Cramer CJ, Truhlar DG, and French AD. ''Exo-anomeric effects on energies and geometries of different conformations of glucose and related systems in the gas phase and aqueous solution.'' Carbohydr res. 1997 298:1-14. [http://dx.doi.org/10.1016/S0008-6215(96)00297-2 DOI:10.1016/S0008-6215(96)00297-2]
# Johnson2009 pmid=19733839
# Alonso2016 pmid=26889578
# Gloster2006 pmid=17002288
# van_Bueren2009 pmid=18976664
# Hrmova2001 pmid=11709165
# Rajan2004 pmid=15341727
# Varrot2003 pmid=12595701
# Zhou1999 pmid=10508787
# Sulzenbacher1999 pmid=10200171
# Urbanikova2011 pmid=21501386
# Guerin2002 pmid=11884144
# Schubot2004 pmid=14756552
# Suzuki2009 pmid=19279191
# Wan2014 pmid=24419374
# Sandgren2004 pmid=15364577
# Uitdehaag1999 pmid=10331869
# Miyake2003 pmid=12741813
# Harris1993 pmid=8431441
# Allouch2004 pmid=15062085
# Wojtkowiak2013 pmid=23275163
# Papanikolau2001 pmid=11560481
# Prag2000 pmid=10884356
# Vocadlo2001 pmid=11518970
# Karlsen1996 pmid=15299731
# Baldwin1993 pmid=8259514
# Cartmell2008 pmid=18799462
# Fernandez-Leiro2010 pmid=20592022
# Abbott2007 pmid=17397864
# Sakurama2012 pmid=22451675
# Sim2008 pmid=18036614
# Verhaest2007 pmid=17335500
# Amaya2004 pmid=15130470
# Zhu2012 pmid=23015718
# Maksimainen2011 pmid=21130883
# Merceron2012 pmid=23012371
# Gibson2007 pmid=17455176
# Shah2008 pmid=18599462
# Czjzek2005 pmid=16212978
# Godoy2016 pmid=27685756
# Fujimoto2010 pmid=20739278
# Kitago2007 pmid=17905739
# Davies1996 pmid=15299721
# Lyu2014 pmid=24766439
# Karaveg2005 pmid=15713668
# Nerinckx2008 pmid=18619586
# Pluvinage2013 pmid=23921382
# Yuan2005 pmid=15893670
# Hoevel2003 pmid=14517232
# Espina2014 pmid=24816105
# Le_Nours2009 pmid=19089956
# Miyanaga2004 pmid=15292273
# Bianchetti2015 pmid=25752603
# Markovic-Housley2000 pmid=11080624
# Imamura2003 pmid=12618437
# Hill2013 pmid=24297913
# Maehara2014 pmid=24482228
# Miyazaki2016 pmid=27688023
# Touhara2014 pmid=24828502
# Suzuki2016 pmid=26494689
# Golan2004 pmid=14573597
# Meng2003 pmid=14517548
# Ito2011 pmid=21354427
# Hurtado-Gerrero2009 pmid=19097997
# Yaoi2007 pmid=17498741
# Martinez-Caballero2023 pmid=37418323
# Thompson2015 pmid=25772148
# Barends2007 pmid=17420245
# Fujimoto2013 pmid=23486481
# Wu2015 pmid=26575439
# Pluvinage2017 pmid=28781080
# Dennis2006 pmid=16565725
# Abbott2009 pmid=19181667
# Hehemann_1_2012 pmid=23150581
# Ficko-Blean2008 pmid=18443291
# Zhu2009 pmid=20081828
# Sogabe2011 pmid=21543843
# Nam2015 pmid=26041776
# Nagae2007 pmid=17459873
# Kitamura2008 pmid=18981178
# Higgins2009 pmid=19608744
# van_Straaten2007 pmid=17502382
# van_Asselt2000 pmid=10684641
# Ndeh2017 pmid=28329766
# Labourel2019 pmid=30877196
# Nakajima2024 Nakajima M. et al. ''Extensive distribution of β-1,2-glucanases: finding of new glycoside hydrolase families of β-1,2-glucanases.'' BioRxiv preprint 2024. https://doi.org/10.1101/2024.02.06.578578
# Luis2018 pmid=29255254
# Bule2019 pmid=31645552
# Jin2016 Jin Y, Petricevic M, John A, Raich L, Jenkins H, Portela De Souza L, Cuskin F, Gilbert HJ, Rovira C, Goddard-Borger ED, Williams SJ, and Davies GJ. ''A β-Mannanase with a Lysozyme-like Fold and a Novel Molecular Catalytic Mechanism.'' ACS Cent Sci. 2016 Nov [http://dx.doi.org/10.1021/acscentsci.6b00232 DOI:10.1021/acscentsci.6b00232]
# Yamada2017 pmid=28392148
# Ohnuma2014 pmid=24582745
# Thompson2012 pmid=22219371
# Xie2016 pmid=27777307
# Gregg2015 pmid=26304114
# Williams2014 pmid=24339341
# Pengthaisong2023 pmid=37180965
# Hehemann_2_2012 pmid=22393053
# Huang2012 pmid=22992047
# Noach2016 pmid=27038508
# Urresti2018 pmid=30084399
# Alonso-Gil2016 pmid=28026180
# Huang2014 Huang CH, Zhu Z, Cheng YS, Chan HC, Ko TP, Chen CC, Wang I, Ho MR, Hsu ST, Zeng YF, Huang YN, Liu JR, Guo RT. ''Structure and Catalytic Mechanism of a Glycoside Hydrolase Family-127 β-L-Arabinofuranosidase (HypBA1).'' J Bioprocess Biotech. 2014 4:171 [http://dx.doi.org/10.4172/2155-9821.1000171 DOI:10.4172/2155-9821.1000171]
# Tsuda2015 pmid=26632508
# Zhai2016 pmid=27088557
# Barbirz2008 pmid=18547389
# Tanaka2019 pmid=30926603
# Armstrong2020 pmid=31871050
# Chen2024 pmid=38795894
# Santos2020 pmid=32451508
# Sato2017 pmid=28546425
# Kashima2021 pmid=34688653
# McGuire2020 pmid=33127644
# Shuoker2023 pmid=37005422
# Shimokawa2023 pmid=37726269
# Motouchi2023 pmid=37735577
</biblio>
[[Category:Definitions and explanations]]

Syn/anti lateral protonation

2025-04-15T12:33:22Z

Wim Nerinckx: GH73 syn, GH124 syn, GH129 anti, GH133 anti, GH168 syn.

{{CuratorApproved}}
* [[Author]]: [[User:Wim Nerinckx|Wim Nerinckx]]
* [[Responsible Curator]]: [[User:Spencer Williams|Spencer Williams]]

----

== Overview ==

This page provides a table that summarizes the spatial positioning of the catalytic [[general acid]] residue in the active sites of [[glycoside hydrolase]]s, relative to the substrate. The table below updates those found in the seminal paper on this concept by Heightman and Vasella <cite>HeightmanVasella1999</cite>, and a following paper by Nerinckx ''et al.'' <cite>Nerinckx2005</cite>.

== Background ==

The ''"not from above, but from the side"'' concept of semi-lateral glycosidic oxygen [[General_acid/base|protonation]] by [[glycoside hydrolase]]s was introduced by Heightman and Vasella <cite>HeightmanVasella1999</cite>. It was originally only described for [[Anomeric centre (alpha and beta)|beta]]-equatorial [[glycoside hydrolase]]s, but appears to be equally applicable to enzymes acting on an [[Anomeric centre (alpha and beta)|alpha]]-axial glycosidic bond <cite>Nerinckx2005</cite>. When dividing [[Sub-site nomenclature|subsite -1]] into half-spaces by a plane defined by the glycosidic oxygen and C1' and H1' of the –1 glycoside, many ligand-complexed structures reveal that the [[General_acid/base|proton donor]] is positioned either in the ''syn'' half-space (near the ring-oxygen of the –1 glycoside), or in the ''anti'' half-space (on the opposite side of the ring-oxygen). Members of the same GH [[Families|family]] appear to share a common ''syn'' or ''anti'' [[General_acid/base|protonator]] arrangement and further, this specificity appears to be preserved within [[Clans|Clans]] of [[Families|families]]. This page's compilation of [[Sub-site nomenclature|subsite -1]] occupied complexes shows that about 70% of all GH [[Families|families]] are ''anti'' [[General_acid/base|protonators]].

Closer inspection of crystal structures of [[Sub-site nomenclature|–1/+1 subsite]]-spanning substrates, or substrate-analogue ligands, in complex with enzymes reveals a further intriguing corollary <cite>Nerinckx2005 Wu2012</cite>. In substrate-bound complexes with ''anti'' [[General_acid/base|protonating]] GH enzymes, the scissile [[Anomeric centre (alpha and beta)|anomeric bond]] (often studied using the thio-analogue) shows a dihedral angle φ (O5'-C1'-[O,S]x-Cx) that is in the lowest-energy synclinal (gauche) conformation. The rationale for this is that a minus synclinal dihedral angle φ for an equatorial glycosidic bond, or plus synclinal for an axial glycosidic bond <cite>Perez1978</cite>, allows for hyperconjugative overlap of the C1'-O5' antibonding orbital with an antiperiplanar-oriented lone pair orbital lobe of the glycosidic oxygen, thereby creating partial double bond character and stabilization of the glycosidic bond by 4–5 kcal/mol; this ground-state stabilizing phenomenon is known as the ‘exo-anomeric effect’ <cite>Cramer1997 Johnson2009 Alonso2016</cite>. ''Anti'' [[General_acid/base|protonation]] occurs on the glycosidic oxygen’s antiperiplanar lone pair, thereby removing the stabilizing exo-anomeric effect. This suggests that ''anti'' [[General_acid/base|protonation]] is an enzymic approach for lowering the activation barrier leading to the [[Transition state|transition state]] (Figure 1 centre).

''Syn'' [[General_acid/base|protonating]] [[glycoside hydrolase]]s apparently make use of a different approach <cite>Nerinckx2005 Wu2012</cite>. In many [[Sub-site nomenclature|–1/+1 subsite]]-spanning ligand complexes, the dihedral angle φ of the scissile anomeric bond has been rotated away from its lowest-energy synclinal position: clockwise to minus-anticlinal or antiperiplanar for beta-equatorial; counterclockwise to plus-anticlinal or antiperiplanar for alpha-axial [[Anomeric centre (alpha and beta)|anomeric bonds]]. This removes the hyperconjugative overlap and thus also the stabilizing exo-anomeric effect. And because of this rotation, a lone pair of the glycosidic oxygen is directed into the ''syn'' half-space, allowing it to be protonated by the ''syn''-positioned [[General_acid/base|proton donor]] (Figure 1 right).

[[File:Syn_anti.jpg|800px|thumb|center|Figure 1. Newman projections, with the glycosidic oxygen as proximal atom and the anomeric carbon as distal atom, showing ''anti'' (centre) versus ''syn'' (right) semi-lateral [[General_acid/base|protonation]] in beta-equatorial (top) and alpha-axial (bottom) [[glycoside hydrolase]]s. The indicated φ is the dihedral angle for O5'-C1'-O4-C4.]]

== Table of ''syn/anti'' protonation examples ==

This table contains only one example per GH [[Families|family]] of a ligand-complexed protein structure where the ''syn'' or ''anti'' positioning of the [[General_acid/base|proton donor]] can be clearly observed; other examples may be available on a [[Families|family-by-family]] basis. The reader is thus advised to consult the [http://www.cazy.org/fam/acc_GH.html#table CAZy database] for a current, comprehensive list of CAZyme structures. Where available, the selected examples are Michaelis-type complexes with the ligand spanning the [[Sub-site nomenclature|-1/+1 subsites]], since these have an intact glycosidic or thioglycosidic bond, or are ''N''-analogs of the substrate (''e.g.'' acarbose). In some examples, the [[General_acid/base|proton donor]] has been mutated (''e.g.'', to the corresponding amide or to an alanine), and in those cases one may wish to look at a superposition of the given PDB example with the structure of the native enzyme. If a Michaelis-type complex is not yet available, the second and third example choices, respectively, are trapped glycosyl-enzyme [[intermediate]]s and product complexes where [[Sub-site nomenclature|subsite -1]] is occupied.

''Please also be aware that this is a large table with many data. Please contact the page Author or Responsible Curator with corrections.''

=== Table ===
This table can be re-sorted by clicking on the icons in the header (''javascript must be turned on in your browser''). To reset the page to be sorted by GH family, click the ''View'' tab at the very top of the page.

{| {{Prettytable}} class="sortable"
|- valign="top"
! '''Family'''
! '''Clan'''
! '''Structure fold '''
! '''Anomeric specificity'''
! '''Mechanism'''
! '''''Syn/anti'' protonator'''
! '''Example PDB ID'''
! '''Enzyme'''
! '''Organism'''
! '''Ligand'''
! '''General acid'''
! '''Nucleophile or General base'''
! '''Reference'''
|-
| [[GH1]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2cer 2cer]
| β-glycosidase S
| ''Sulfolobus solfataricus'' P2
| phenethyl glucoimidazole
| '''Glu206'''
| Glu387
| <cite>Gloster2006</cite>
|-
| [[GH2]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vzu 2vzu]
| exo-β-glucosaminidase
| ''Amicolatopsis orientalis''
| PNP-β-{{Smallcaps|d}}-glucosamine
| '''Glu469'''
| Glu541
| <cite>van_Bueren2009</cite>
|-
| [[GH3]]
| none
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1iex 1iex]
| exo-1,3-1,4-glucanase
| ''Hordeum vulgare''
| thiocellobiose
| '''Glu491'''
| Asp285
| <cite>Hrmova2001</cite>
|-
| [[GH4]]
| none
| Rossmann + α6/β3 + β3/α4
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1u8x 1u8x]
| 6-P-α-glucosidase
| ''Bacillus subtilis''
| alpha-{{Smallcaps|d}}-glucose-6-phosphate
| '''Asp172'''
| not applicable
| <cite>Rajan2004</cite>
|-
| [[GH5]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1h2j 1h2j]
| endo-β-1,4-glucanase
| ''Bacillus agaradhaerens''
| 2',4'-DNP-2-F-cellobioside
| '''Glu129'''
| Glu228
| <cite>Varrot2003</cite>
|-
| [[GH6]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1qjw 1qjw]
| cellobiohydrolase 2
| ''Hypocrea jecorina''
| (Glc)2-S-(Glc)2
| '''Asp221'''
| debated
| <cite>Zhou1999</cite>
|-
| [[GH7]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1ovw 1ovw]
| endo-1,4-glucanase
| ''Fusarium oxysporum''
| thio-(Glc)5
| '''Glu202'''
| Glu197
| <cite>Sulzenbacher1999</cite>
|-
| [[GH8]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1kwf 1kwf]
| endo-1,4-glucanase
| ''Clostridium thermocellum''
| cellopentaose
| '''Glu95'''
| Asp278
| <cite>Guerin2002</cite>
|-
| [[GH9]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1rq5 1rq5]
| cellobiohydrolase
| ''Clostridium thermocellum''
| cellotetraose
| '''Glu795'''
| Asp383
| <cite>Schubot2004</cite>
|-
| [[GH10]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2d24 2d24]
| β-1,4-xylanase
| ''Streptomyces olivaceoviridis'' E-86
| xylopentaose
| '''Glu128'''
| Glu236
| <cite>Suzuki2009</cite>
|-
| [[GH11]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}4hk8 4hk8]
| endo-β-1,4-xylanase
| ''Hypocrea jecorina''
| xylohexaose
| '''Glu177'''
| Glu86
| <cite>Wan2014</cite>
|-
| [[GH12]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1w2u 1w2u]
| endoglucanase
| ''Humicola grisea''
| thiocellotetraose
| '''Glu205'''
| Glu120
| <cite>Sandgren2004</cite>
|-
| [[GH13]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1cxk 1cxk]
| β-cyclodextrin glucanotransferase
| ''Bacillus circulans''
| maltononaose
| '''Glu257'''
| Asp229
| <cite>Uitdehaag1999</cite>
|-
| [[GH14]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1itc 1itc]
| β-amylase
| ''Bacillus cereus''
| maltopentaose
| '''Glu172'''
| Glu367
| <cite>Miyake2003</cite>
|-
| [[GH15]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1dog 1dog]
| glucoamylase
| ''Aspergillus awamori''
| 1-deoxynojirimycin
| '''Glu179'''
| Glu400
| <cite>Harris1993</cite>
|-
| [[GH16]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1urx 1urx]
| β-agarase A
| ''Zobellia galactanivorans''
| oligoagarose
| '''Glu152'''
| Glu147
| <cite>Allouch2004</cite>
|-
| [[GH17]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzj 4gzj]
| endo-β-1,3-glucanase
| ''Solanum tuberosum''
| laminaratriose + laminarabiose
| '''Glu118'''
| Glu259
| <cite>Wojtkowiak2013</cite>
|-
| [[GH18]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1ffr 1ffr]
| chitinase A
| ''Serratia marcescens''
| (NAG)6
| '''Glu315'''
| internal
| <cite>Papanikolau2001</cite>
|-
| [[GH19]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}3wh1 3wh1]
| chitinase
| ''Bryum coronatum''
| (GlcNAc)4
| '''Glu61'''
| Glu70
| <cite>Ohnuma2014</cite>
|-
| [[GH20]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1c7s 1c7s]
| chitobiase
| ''Serratia marcescens''
| chitobiose
| '''Glu540'''
| internal
| <cite>Prag2000</cite>
|-
| [[GH22]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1h6m 1h6m]
| lysozyme C
| ''Gallus gallus''
| Chit-2-F-chitosyl
| '''Glu35'''
| Asp52
| <cite>Vocadlo2001</cite>
|-
| [[GH23]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1lsp 1lsp]
| lysozyme G
| ''Cygnus atratus''
| Bulgecin A
| '''Glu73'''
| internal
| <cite>Karlsen1996</cite>
|-
| [[GH24]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}148l 148l]
| lysozyme E
| Bacteriophage T4
| chitobiosyl
| '''Glu11'''
| Glu26
| <cite>Baldwin1993</cite>
|-
| [[GH26]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vx6 2vx6]
| exo-β-mannanase
| ''Cellvibrio japonicus'' Ueda107
| Gal1Man4
| '''Glu221'''
| Glu338
| <cite>Cartmell2008</cite>
|-
| [[GH27]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}} / beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3lrm 3lrm]
| α-galactosidase
| ''Saccharomyces cerevisiae''
| raffinose
| '''Asp209'''
| Asp141
| <cite>Fernandez-Leiro2010</cite>
|-
| [[GH28]]
| N
| β-helix
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}2uvf 2uvf]
| exo-polygalacturonosidase
| ''Yersinia enterocolitica'' ATCC9610D
| digalacturonic acid
| '''Asp402'''
| Asp381 Asp403
| <cite>Abbott2007</cite>
|-
| [[GH29]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| '''''syn'''''
| [{{PDBlink}}3uet 3uet]
| α-1,3/4-fucosidase
| ''Bifidobacterium longum'' subsp. infantis
| lacto-''N''-fucopentaose II
| '''Glu217'''
| Asp172
| <cite>Sakurama2012</cite>
|-
| [[GH30]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2y24 2y24]
| glucurono-xylanase
| ''Dickea chrysanthemi'' D1
| glucuronoxylan tetrasaccharide
| '''Glu163'''
| Glu253
| <cite>Urbanikova2011</cite>
|-
| [[GH31]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2qmj 2qmj]
| maltase-glucoamylase
| ''Homo sapiens''
| acarbose
| '''Asp542'''
| Asp443
| <cite>Sim2008</cite>
|-
| [[GH32]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2add 2add]
| fructan β-(2,1)-fructosidase
| ''Cichorium intybus''
| sucrose
| '''Glu201'''
| Asp22
| <cite>Verhaest2007</cite>
|-
| [[GH33]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1s0i 1s0i]
| transsialidase
| ''Trypanosoma cruzi''
| sialyllactose
| '''Asp59'''
| Tyr342 (with Glu230)
| <cite>Amaya2004</cite>
|-
| [[GH34]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzw 4gzw]
| N2 neuraminidase
| ''Influenza'' A Tanzania/205/2010 H3N2
| α-{{Smallcaps|d}}-Neup5Ac-(2,3)-β-{{Smallcaps|d}}-Galp-(1,4)-β-{{Smallcaps|d}}-GlcpNAc
| '''Asp151'''
| Tyr406 (with Glu277)
| <cite>Zhu2012</cite>
|-
| [[GH35]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3ogv 3ogv]
| β-galactosidase
| ''Hypocrea jecorina''
| 2-phenylethyl 1-thio-β-{{Smallcaps|d}}-galactopyranoside
| '''Glu200'''
| Glu298
| <cite>Maksimainen2011</cite>
|-
| [[GH36]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4fnu 4fnu]
| β-galactosidase
| ''Geobacillus stearothermophilus''
| stachyose
| '''Asp584'''
| Asp478
| <cite>Merceron2012</cite>
|-
| [[GH37]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2jf4 2jf4]
| trehalase
| ''Escherichia coli''
| validoxylamine
| '''Asp312'''
| Glu496
| <cite>Gibson2007</cite>
|-
| [[GH38]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3czn 3czn]
| Golgi α-mannosidase II
| ''Drosophila melanogaster''
| GlcNAcMan(5)GlcNAc(2)
| '''Asp341'''
| Asp204
| <cite>Shah2008</cite>
|-
| [[GH39]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2bfg 2bfg]
| β-xylosidase
| ''Geobacillus stearothermophilus''
| 2,5-dinitrophenyl-β-{{Smallcaps|d}}-xyloside
| '''Glu160'''
| Glu278
| <cite>Czjzek2005</cite>
|-
| [[GH42]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ucf 4ucf]
| β-galactosidase
| ''Bifidobacterium bifidum''
| {{Smallcaps|d}}-galactose
| '''Glu161'''
| Glu320
| <cite>Godoy2016</cite>
|-
| [[GH43]]
| F
| 5-fold β-propeller
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3akh 3akh]
| exo-1,5-α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces avermitilis''
| α-1,5-arabinofuranotriose
| '''Glu196'''
| Asp220
| <cite>Fujimoto2010</cite>
|-
| [[GH44]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2eqd 2eqd]
| endoglucanase
| ''Clostridium thermocellum''
| cellooctaose
| '''Glu186'''
| Glu359
| <cite>Kitago2007</cite>
|-
| [[GH45]]
| none
| 6-stranded β-barrel
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4eng 4eng]
| endo-1,4-glucanase
| ''Humicola insolens''
| cellohexaose
| '''Asp121'''
| Asp10
| <cite>Davies1996</cite>
|-
| [[GH46]]
| I
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4olt 4olt]
| chitosanase
| ''Microbacterium sp.'' OU01
| hexa-glucosamine
| '''Glu25'''
| Asp43
| <cite>Lyu2014</cite>
|-
| [[GH47]]
| none
| (α/α)7
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1x9d 1x9d]
| α-mannosidase I
| ''Homo sapiens''
| Me-2-S-(α-Man)-2-thio-α-Man
| '''Asp463'''
| Glu599
| <cite>Karaveg2005</cite>, <cite>Nerinckx2008</cite>
|-
| [[GH48]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH8''
|
|
|
|
|
|
|-
| [[GH49]]
| N
| β-helix
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH28''
|
|
|
|
|
|
|-
| [[GH50]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4bq5 4bq5]
| exo-β-agarase
| ''Saccharophagus degradans''
| neoagarotetraose
| '''Glu535'''
| Glu695
| <cite>Pluvinage2013</cite>
|-
| [[GH51]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1qw9 1qw9]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Geobacillus stearothermophilus''
| PNP-{{Smallcaps|l}}-arabinofuranoside
| '''Glu175'''
| Glu294
| <cite>Hoevel2003</cite>
|-
| [[GH52]]
| O
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| '' predicted perpendicular by clan, see at GH116''
| [{{PDBlink}}4c1p 4c1p]
| β-xylosidase
| ''Geobacillus thermoglucosidasius''
| xylobiose
| '''Asp517'''
| Glu537
| <cite>Espina2014</cite>
|-
| [[GH53]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2ccr 2ccr]
| β-1,4-galactanase
| ''Bacillus licheniformis''
| galactotriose
| '''Glu165'''
| Glu263
| <cite>Le_Nours2009</cite>
|-
| [[GH54]]
| none
| β-sandwich
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1wd4 1wd4]
| α-{{Smallcaps|l}}-arabinofuranosidase B
| ''Aspergillus kawachii''
| {{Smallcaps|l}}-arabinofuranose
| '''Asp297'''
| Glu221
| <cite>Miyanaga2004</cite>
|-
| [[GH55]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4tz5 4tz5]
| exo-β-1,3-glucanase
| ''Streptomyces sp.'' SirexAA-E
| laminarihexaose
| '''Glu502'''
| unknown
| <cite>Bianchetti2015</cite>
|-
| [[GH56]]
| none
| (β/α)7
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1fcv 1fcv]
| hyaluronidase
| ''Apis mellifera''
| (hyaluron.)4
| '''Glu113'''
| internal
| <cite>Markovic-Housley2000</cite>
|-
| [[GH57]]
| T
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1k1y 1k1y]
| glucanotransferase
| ''Thermococcus litoralis''
| acarbose
| '''Asp214'''
| Glu123
| <cite>Imamura2003</cite>
|-
| [[GH59]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ccc 4ccc]
| β-galactocerebrosidase
| ''Mus musculus''
| PNP-β-{{Smallcaps|d}}-galactoside
| '''Glu182'''
| Glu258
| <cite>Hill2013</cite>
|-
| [[GH62]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3wn0 3wn0]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces coelicolor''
| β-{{Smallcaps|l}}-Arabinofuranose
| '''Glu361'''
| Asp202
| <cite>Maehara2014</cite>
|-
| [[GH63]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5ca3 5ca3]
| α-glucosidase
| ''Escherichia coli''
| glucose and lactose
| '''Asp501'''
| Glu727
| <cite>Miyazaki2016</cite>
|-
| [[GH65]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}4ktr 4ktr]
| 2-O-α-glucosylglycerol phosphorylase
| ''Bacillus selenitireducens''
| isofagomine
| '''Glu475'''
| phosphate
| <cite>Touhara2014</cite>
|-
| [[GH66]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5axh 5axh]
| dextranase
| ''Thermoanaerobacter pseudethanolicus''
| isomaltohexaose
| '''Glu374'''
| Asp312
| <cite>Suzuki2016</cite>
|-
| [[GH67]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1l8n 1l8n]
| α-glucuronidase
| ''Geobacillus stearothermophilus''
| 4-O-methyl-{{Smallcaps|d}}-glucuronic acid and xylotriose
| '''Glu286'''
| Asp364 Glu392
| <cite>Golan2004</cite>
|-
| [[GH68]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1pt2 1pt2]
| levansucrase
| ''Bacillus subtilis''
| sucrose
| '''Glu342'''
| Asp86
| <cite>Meng2003</cite>
|-
| [[GH70]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3aic 3aic]
| glucansucrase
| ''Streptococcus mutans''
| α-acarbose
| '''Glu515'''
| Asp477
| <cite>Ito2011</cite>
|-
| [[GH72]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w62 2w62]
| β-1,3-glucanotransferase
| ''Saccharomyces cerevisiae'' S288C
| laminaripentaose
| '''Glu176'''
| Glu275
| <cite>Hurtado-Gerrero2009</cite>
|-

| [[GH73]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| unknown
| '''''syn'''''
| [{{PDBlink}}7pod 7pod]
| peptidoglycan endo-β-1,4-''N''-acetylglucosaminidase
| ''Streptococcus pneumoniae'' R6
| NAG-NAM-NAG-NAM tetrasaccharide
| '''Glu585'''
| unknown
| <cite>Martinez-Caballero2023</cite>
|-

| [[GH74]]

| none
| 7-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}2ebs 2ebs]
| cellobiohydrolase (OXG-RCBH)
| ''Geotrichum sp.'' m128
| xyloglucan heptasaccharide
| '''Asp465'''
| Asp35
| <cite>Yaoi2007</cite>
|-
| [[GH76]]
| none
| (α/α)6
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5agd 5agd]
| endo-α-1,6-mannanase
| ''Bacillus circulans''
| α-1,6-mannopentaose
| '''Asp125'''
| Asp124
| <cite>Thompson2015</cite>
|-
| [[GH77]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2oww 2oww]
| 4-α-glucanotransferase
| ''Thermus thermofilus''
| acarbose + 4-deoxy-α-{{Smallcaps|d}}-glucose
| '''Glu340'''
| Asp293
| <cite>Barends2007</cite>
|-
| [[GH78]]
| H
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3w5n 3w5n]
| α-{{Smallcaps|l}}-rhamnosidase
| ''Streptomyces avermitilis''
| {{Smallcaps|l}}-rhamnose
| '''Glu636'''
| Glu895
| <cite>Fujimoto2013</cite>
|-
| [[GH79]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5e9c 5e9c]
| heparanase
| ''Homo sapiens''
| heparin tetrasaccharide
| '''Glu225'''
| Glu343
| <cite>Wu2015</cite>
|-
| [[GH80]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH24''
|
|
|
|
|
|
|-
| [[GH81]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5t4g 5t4g]
| endo-β-1,3-glucanase
| ''Bacillus halodurans'' C-125
| laminarin
| '''Asp466'''
| Glu542
| <cite>Pluvinage2017</cite>
|-
| [[GH83]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1z4x 1z4x]
| hemagglutinin-neuraminidase
| Simian virus 5
| α-2,3-sialyllactose
| '''Asp187''' on flexible loop
| Tyr523 (with Glu390)
| <cite>Yuan2005</cite>
|-
| [[GH84]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2chn 2chn]
| β-''N''-acetyl-glucosaminidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| NAG-thiazoline
| '''Glu242'''
| internal
| <cite>Dennis2006</cite>
|-
| [[GH85]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w92 2w92]
| endo-β-''N''-acetyl-glucosaminidase D
| ''Streptococcus pneumoniae'' TIGR4
| NAG-thiazoline
| '''Glu337'''
| internal
| <cite>Abbott2009</cite>
|-
| [[GH86]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4aw7 4aw7]
| β-porphyranase
| ''Bacteroides plebeius''
| porphyran fragment
| '''Glu152'''
| Glu279
| <cite>Hehemann_1_2012</cite>
|-
| [[GH89]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vcb 2vcb]
| α-''N''-acetyl-glucosaminidase
| ''Clostridium perfringens''
| PUGNAc
| '''Glu483'''
| Glu601
| <cite>Ficko-Blean2008</cite>
|-
| [[GH92]]
| none
| (α/α)6 and β-sandwich
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ww1 2ww1]
| α-1,2-mannosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| thiomannobioside
| '''Glu533'''
| Asp644 Asp642
| <cite>Zhu2009</cite>
|-
| [[GH93]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3a72 3a72]
| exo-arabinanase
| ''Penicillium chrysogenum''
| arabinobiose
| '''Glu246'''
| Glu174
| <cite>Sogabe2011</cite>
|-
| [[GH94]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4zli 4zli]
| cellobionic acid phosphorylase
| ''Saccharophagus degradans''
| 3-O-β-{{Smallcaps|d}}-glucopyranosyl-α-{{Smallcaps|d}}-glucopyranuronic acid
| '''Asp472'''
| phosphate
| <cite>Nam2015</cite>
|-
| [[GH95]]
| none
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ead 2ead]
| α-1,2-{{Smallcaps|l}}-fucosidase
| ''Bifidobacterium bifidum''
| Fuc-α-1,2-Gal
| '''Glu566'''
| Asn423 Asp766
| <cite>Nagae2007</cite>
|-
| [[GH97]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining + inverting
| '''''anti'''''
| [{{PDBlink}}2zq0 2zq0]
| α-glucosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| acarbose
| '''Glu532'''
| Glu508
| <cite>Kitamura2008</cite>
|-
| [[GH98]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2wmg 2wmg]
| endo-β-1,4-galactosidase
| ''Streptococcus pneumoniae''
| A-LewisY pentasaccharide
| '''Glu158'''
| Asp251 Glu301
| <cite>Higgins2009</cite>
|-
| [[GH99]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ad4 4ad4]
| endo-α-mannosidase
| ''Bacteroides xylanisolvens''
| glucose-1,3-isofagomine and α-1,2- mannobiose
| '''Glu336'''
| debated
| <cite>Thompson2012</cite>
|-
| [[GH100]]
| G
| (α/α)6 core
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5gop 5gop]
| invertase
| ''Anabaena (Nostoc) sp.'' pcc7120
| sucrose
| '''Asp188'''
| Glu414
| <cite>Xie2016</cite>
|-
| [[GH101]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5a56 5a56]
| endo-α-N-acetylgalactosaminidase
| ''Streptococcus pneumoniae'' TIGR4
| β-{{Smallcaps|d}}-Galp-(1-3)-α-{{Smallcaps|d}}-GalpNAc-(1)-methyl
| '''Glu796''' +water
| Asp764
| <cite>Gregg2015</cite>
|-
| [[GH102]]
| none
| double-ψ β-barrel
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}2pi8 2pi8]
| lytic transglycosylase A
| ''Escherichia coli''
| chitohexaose
| '''Asp308'''
| none
| <cite>van_Straaten2007</cite>
|-
| [[GH103]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1d0k 1d0k]
| lytic transglycosylase SLT35
| ''Escherichia coli''
| murodipeptides
| '''Glu162'''
| internal
| <cite>van_Asselt2000</cite>
|-
| [[GH106]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5mwk 5mwk]
| α-{{Smallcaps|l}}-rhamnosidase BT_0986
| ''Bacteroides thetaiotaomicron''
| pectin heptasaccharide
| '''Glu461'''
| Glu593 or Glu561
| <cite>Ndeh2017</cite>
|-
| [[GH107]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| ''predicted syn by clan''
| ''see at GH29''
|
|
|
|
|
|
|-
| [[GH110]]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}7jwf 7jwf]
| α-1,3-galactosidase
| ''Pseudoalteromonas distincta''
| Gal-α1,3-Gal
| '''Asp344'''
| Asp321 Asp345
| <cite>McGuire2020</cite>
|-
| [[GH113]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4cd8 4cd8]
| β-mannanase
| ''Alicyclobacillus acidocaldarius''
| mannobioimidazole
| '''Glu151'''
| Glu231
| <cite>Williams2014</cite>
|-
| [[GH116]]
| O
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''perpendicular''''' (anomaly)
| [{{PDBlink}}8i5u 8i5u]
| β-glucosidase
| ''Thermoanaerobacterium xylanolyticum'' LX-11
| laminaribiose
| '''Asp593'''
| Glu441
| <cite>Pengthaisong2023</cite>
|-
| [[GH117]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}4ak7 4ak7]
| α-1,3-3,6-anhydro-{{Smallcaps|l}}-galactosidase
| ''Bacteroides plebeius''
| neoagarobiose
| '''His302''' (relay from Asp320)
| Asp90
| <cite>Hehemann_2_2012</cite>
|-
| [[GH119]]
| T
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at GH57''
|
|
|
|
|
|
|-
| [[GH120]]
| none
| parallel β-helix and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3vsv 3vsv]
| β-xylosidase XylC
| ''Thermoanaerobacterium saccharolyticum'' JW/SL-YS485
| {{Smallcaps|d}}-xylose
| '''Glu405'''
| Asp382
| <cite>Huang2012</cite>
|-
| [[GH123]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5fr0 5fr0]
| exo-β-N-acetyl-galactosaminidase
| ''Clostridium perfringens''
| ''N''-difluoroacetyl-{{Smallcaps|d}}-galactosamine
| '''Glu345'''
| internal
| <cite>Noach2016</cite>
|-

| [[GH124]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}6g1i 6g1i]
| endo-β-1,4-glucanase
| ''Acetivibrio thermocellus'' ATCC 27405
| fructosylated cellopentaose
| '''Glu203'''
| unknown
| <cite>Urresti2018</cite>
|-

| [[GH125]]

| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5m7y 5m7y]
| exo-α-1,6-mannosidase
| ''Clostridium perfringens''
| 1,6-α-mannotriose
| '''Asp220'''
| Glu393
| <cite>Alonso-Gil2016</cite>
|-
| [[GH127]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3wrg 3wrg]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bifidobacterium longum''
| {{Smallcaps|l}}-arabinose
| '''Glu322'''
| Cys417
| <cite>Huang2014</cite>
|-
| [[GH128]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}6ufl 6ufl]
| β-1,3-glucanase
| ''Amycolatopsis mediterranei''
| laminarihexaose
| '''Glu102'''
| Glu199
| <cite>Santos2020</cite>
|-

| [[GH129]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5wzn 5wzn]
| exo-α-''N''-acetylgalactosaminidase (NagBb)
| ''Bifidobacterium bifidum'' JCM 1254
| GalNAc
| '''Glu478'''
| Asp435
| <cite>Sato2017</cite>
|-

| [[GH130]]

| none
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5b0s 5b0s]
| β-1,2-mannobiose phosphorylase
| ''Listeria innocua''
| β-1,2-mannotriose
| '''Asp141''' relay
| phosphate
| <cite>Tsuda2015</cite>
|-

| [[GH133]]
| none
| (α/α)6
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5d0f 5d0f]
| glycogen-debranching enzyme
| ''Nakaseomyces glabratus'' CBS 138
| maltopentaose
| '''Glu564'''
| Asp535
| <cite>Zhai2016</cite>
|-

| [[GH134]]

| none
| β + α
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5jug 5jug]
| β-mannanase
| ''Streptomyces sp.''
| mannopentaose
| '''Glu45'''
| Asp57
| <cite>Jin2016</cite>
|-
| [[GH136]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}5gqf 5gqf]
| lacto-N-biosidase
| ''Bifidobacterium longum''
| lacto-N-biose
| '''Asp411'''
| Asp418
| <cite>Yamada2017</cite>
|-
| [[GH137]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|l}}
| unknown
| '''''anti'''''
| [{{PDBlink}}5mui 5mui]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0996
| ''Bacteroides thetaiotaomicron''
| pectin oligosaccharide
| '''Glu240'''
| Glu159
| <cite>Ndeh2017</cite>
|-
| [[GH138]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}6hzg 6hzg]
| α-1,2-{{Smallcaps|d}}-galacturonidase
| ''Bacteroides paurosaccharolyticus''
| alpha-{{Smallcaps|d}}-galactopyranuronic
| '''Glu294'''
| Glu361
| <cite>Labourel2019</cite>
|-
| [[GH140]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH144]]
| S
| (α/α)8
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}8xul 8xul]
| beta-1,2-glucanase
| ''Xanthomonas campestris''
| beta-1,2-glucoheptasaccharide
| '''Glu239'''
| unknown
| <cite>Nakajima2024</cite>
|-
| [[GH146]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5opj 5opj]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bacteroides thetaiotaomicron''
| {{Smallcaps|l}}-arabinose
| '''Glu320'''
| Cys416
| <cite>Luis2018</cite>
|-
| [[GH147]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH148]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH149]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH156]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}6s0e 6s0e]
| exo-α-sialidase
| uncultured bacterium pG7
| N-acetyl-2,3-dehydro-2-deoxyneuraminic acid
| '''His134''' (relay from Asp132)
| Asp14
| <cite>Bule2019</cite>
|-
| [[GH157]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH158]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH161]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH162]]
| S
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}6imw 6imw]
| endo-β-1,2-glucanase
| ''Talaromyces funiculosus''
| beta-1,2-glucan
| '''Glu262''' via C3-OH of glc at subs. +2
| Asp446
| <cite>Tanaka2019</cite>
|-
| [[GH164]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}6t75 6t75]
| β-mannosidase
| ''Bacteroides salyersiae''
| 2-deoxy-2-F-mannosyl
| '''Glu160'''
| Glu297
| <cite>Armstrong2020</cite>
|-
| [[GH167]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|-

| [[GH168]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| '''''syn'''''
| [{{PDBlink}}8ya7 8ya7]
| endo-α-1,3-{{Smallcaps|l}}-fucanase (Fun168A)
| ''Wenyingzhuangia fucanilytica'' CZ1127
| sulfated fucotetraose
| '''Glu264'''
| Asp206
| <cite>Chen2024</cite>
|-

| [[GH169]]

| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH172]]
| none
| β-jelly roll
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}7v1w 7v1w]
| difructose-anhydride synthase
| ''Bifidobacterium dentum''
| beta-{{Smallcaps|d}}-arabinofuranose
| '''Glu270'''
| Glu291
| <cite>Kashima2021</cite>
|-
| [[GH173]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH178]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at e.g. GH15''
|
|
|
|
|
|-
| [[GH181]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}8axi 8axi]
| exo-α-sialidase
| ''Akkermansia muciniphila''
| 2-deoxy-2,3-dehydro-''N''-acetyl-neuraminic acid + T-antigen disaccharide
| '''Asp345'''
| Glu218
| <cite>Shuoker2023</cite>
|-
| [[GH183]]
| none
| 5-bladed β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}8ic1 8ic1]
| endo-α-1,5-{{Smallcaps|d}}-arabinofuranosidase
| ''Microbacterium arabinogalactanolyticum'' JCM 9171
| α-{{Smallcaps|d}}-Araf-(1,5)-α-{{Smallcaps|d}}-Araf-(1,5)-α-{{Smallcaps|d}}-Araf-(1,5)-α-{{Smallcaps|d}}-Araf
| '''Asp51'''
| Asp33
| <cite>Shimokawa2023</cite>
|-
| [[GH186]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}8ip1 8ip1]
| β-1,2-glucanase
| ''Escherechia coli''
| β-1,2-glucan
| '''Asp388'''
| Asp300 + 3 waters
| <cite>Motouchi2023</cite>
|-
| [http://www.cazy.org/GH0.html n.c.*]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2vjj 2vjj]
| endo-α-N-acetylglucosaminidase
| Bacteriophage HK620
| O18A1 O-antigen hexasaccharide
| '''Asp339'''
| Glu372
| <cite>Barbirz2008</cite>
|}
<nowiki>*</nowiki> n.c.: Found among the collection of [http://www.cazy.org/GH0.html non-classified GH sequences in the CAZy Database].

== References ==

<biblio>
# HeightmanVasella1999 Heightman TD and Vasella AT. ''Recent Insights into Inhibition, Structure, and Mechanism of Configuration-Retaining Glycosidases.'' Angew Chem Int Ed. 1999 38(6):750-770. [http://www3.interscience.wiley.com/journal/55000581/abstract Article online].
# Nerinckx2005 pmid=15642336
# Wu2012 pmid=23137336
# Perez1978 Pérez S and Marchessault RH. ''The exo-anomeric effect: experimental evidence from crystal structures.'' Carbohydr res. 1978 65:114-120. [http://dx.doi.org/10.1016/S0008-6215(00)84218-4 DOI:10.1016/S0008-6215(00)84218-4]
# Cramer1997 Cramer CJ, Truhlar DG, and French AD. ''Exo-anomeric effects on energies and geometries of different conformations of glucose and related systems in the gas phase and aqueous solution.'' Carbohydr res. 1997 298:1-14. [http://dx.doi.org/10.1016/S0008-6215(96)00297-2 DOI:10.1016/S0008-6215(96)00297-2]
# Johnson2009 pmid=19733839
# Alonso2016 pmid=26889578
# Gloster2006 pmid=17002288
# van_Bueren2009 pmid=18976664
# Hrmova2001 pmid=11709165
# Rajan2004 pmid=15341727
# Varrot2003 pmid=12595701
# Zhou1999 pmid=10508787
# Sulzenbacher1999 pmid=10200171
# Urbanikova2011 pmid=21501386
# Guerin2002 pmid=11884144
# Schubot2004 pmid=14756552
# Suzuki2009 pmid=19279191
# Wan2014 pmid=24419374
# Sandgren2004 pmid=15364577
# Uitdehaag1999 pmid=10331869
# Miyake2003 pmid=12741813
# Harris1993 pmid=8431441
# Allouch2004 pmid=15062085
# Wojtkowiak2013 pmid=23275163
# Papanikolau2001 pmid=11560481
# Prag2000 pmid=10884356
# Vocadlo2001 pmid=11518970
# Karlsen1996 pmid=15299731
# Baldwin1993 pmid=8259514
# Cartmell2008 pmid=18799462
# Fernandez-Leiro2010 pmid=20592022
# Abbott2007 pmid=17397864
# Sakurama2012 pmid=22451675
# Sim2008 pmid=18036614
# Verhaest2007 pmid=17335500
# Amaya2004 pmid=15130470
# Zhu2012 pmid=23015718
# Maksimainen2011 pmid=21130883
# Merceron2012 pmid=23012371
# Gibson2007 pmid=17455176
# Shah2008 pmid=18599462
# Czjzek2005 pmid=16212978
# Godoy2016 pmid=27685756
# Fujimoto2010 pmid=20739278
# Kitago2007 pmid=17905739
# Davies1996 pmid=15299721
# Lyu2014 pmid=24766439
# Karaveg2005 pmid=15713668
# Nerinckx2008 pmid=18619586
# Pluvinage2013 pmid=23921382
# Yuan2005 pmid=15893670
# Hoevel2003 pmid=14517232
# Espina2014 pmid=24816105
# Le_Nours2009 pmid=19089956
# Miyanaga2004 pmid=15292273
# Bianchetti2015 pmid=25752603
# Markovic-Housley2000 pmid=11080624
# Imamura2003 pmid=12618437
# Hill2013 pmid=24297913
# Maehara2014 pmid=24482228
# Miyazaki2016 pmid=27688023
# Touhara2014 pmid=24828502
# Suzuki2016 pmid=26494689
# Golan2004 pmid=14573597
# Meng2003 pmid=14517548
# Ito2011 pmid=21354427
# Hurtado-Gerrero2009 pmid=19097997
# Yaoi2007 pmid=17498741

# Martinez-Caballero2023 pmid=37418323

# Thompson2015 pmid=25772148

# Barends2007 pmid=17420245
# Fujimoto2013 pmid=23486481
# Wu2015 pmid=26575439
# Pluvinage2017 pmid=28781080
# Dennis2006 pmid=16565725
# Abbott2009 pmid=19181667
# Hehemann_1_2012 pmid=23150581
# Ficko-Blean2008 pmid=18443291
# Zhu2009 pmid=20081828
# Sogabe2011 pmid=21543843
# Nam2015 pmid=26041776
# Nagae2007 pmid=17459873
# Kitamura2008 pmid=18981178
# Higgins2009 pmid=19608744
# van_Straaten2007 pmid=17502382
# van_Asselt2000 pmid=10684641
# Ndeh2017 pmid=28329766
# Labourel2019 pmid=30877196
# Nakajima2024 Nakajima M. et al. ''Extensive distribution of β-1,2-glucanases: finding of new glycoside hydrolase families of β-1,2-glucanases.'' BioRxiv preprint 2024. https://doi.org/10.1101/2024.02.06.578578
# Luis2018 pmid=29255254
# Bule2019 pmid=31645552
# Jin2016 Jin Y, Petricevic M, John A, Raich L, Jenkins H, Portela De Souza L, Cuskin F, Gilbert HJ, Rovira C, Goddard-Borger ED, Williams SJ, and Davies GJ. ''A β-Mannanase with a Lysozyme-like Fold and a Novel Molecular Catalytic Mechanism.'' ACS Cent Sci. 2016 Nov [http://dx.doi.org/10.1021/acscentsci.6b00232 DOI:10.1021/acscentsci.6b00232]
# Yamada2017 pmid=28392148
# Ohnuma2014 pmid=24582745
# Thompson2012 pmid=22219371
# Xie2016 pmid=27777307
# Gregg2015 pmid=26304114
# Williams2014 pmid=24339341
# Pengthaisong2023 pmid=37180965
# Hehemann_2_2012 pmid=22393053
# Huang2012 pmid=22992047
# Noach2016 pmid=27038508

# Urresti2018 pmid=30084399

# Alonso-Gil2016 pmid=28026180

# Huang2014 Huang CH, Zhu Z, Cheng YS, Chan HC, Ko TP, Chen CC, Wang I, Ho MR, Hsu ST, Zeng YF, Huang YN, Liu JR, Guo RT. ''Structure and Catalytic Mechanism of a Glycoside Hydrolase Family-127 β-L-Arabinofuranosidase (HypBA1).'' J Bioprocess Biotech. 2014 4:171 [http://dx.doi.org/10.4172/2155-9821.1000171 DOI:10.4172/2155-9821.1000171]
# Tsuda2015 pmid=26632508

# Zhai2016 pmid=27088557

# Barbirz2008 pmid=18547389

# Tanaka2019 pmid=30926603
# Armstrong2020 pmid=31871050

# Chen2024 pmid=38795894

# Santos2020 pmid=32451508

# Sato2017 pmid=28546425

# Kashima2021 pmid=34688653

# McGuire2020 pmid=33127644
# Shuoker2023 pmid=37005422
# Shimokawa2023 pmid=37726269
# Motouchi2023 pmid=37735577
</biblio>
[[Category:Definitions and explanations]]

Syn/anti lateral protonation

2025-04-08T08:14:45Z

Wim Nerinckx: Update clan-O GH52 and GH116

{{CuratorApproved}}
* [[Author]]: [[User:Wim Nerinckx|Wim Nerinckx]]
* [[Responsible Curator]]: [[User:Spencer Williams|Spencer Williams]]

----

== Overview ==

This page provides a table that summarizes the spatial positioning of the catalytic [[general acid]] residue in the active sites of [[glycoside hydrolase]]s, relative to the substrate. The table below updates those found in the seminal paper on this concept by Heightman and Vasella <cite>HeightmanVasella1999</cite>, and a following paper by Nerinckx ''et al.'' <cite>Nerinckx2005</cite>.

== Background ==

The ''"not from above, but from the side"'' concept of semi-lateral glycosidic oxygen [[General_acid/base|protonation]] by [[glycoside hydrolase]]s was introduced by Heightman and Vasella <cite>HeightmanVasella1999</cite>. It was originally only described for [[Anomeric centre (alpha and beta)|beta]]-equatorial [[glycoside hydrolase]]s, but appears to be equally applicable to enzymes acting on an [[Anomeric centre (alpha and beta)|alpha]]-axial glycosidic bond <cite>Nerinckx2005</cite>. When dividing [[Sub-site nomenclature|subsite -1]] into half-spaces by a plane defined by the glycosidic oxygen and C1' and H1' of the –1 glycoside, many ligand-complexed structures reveal that the [[General_acid/base|proton donor]] is positioned either in the ''syn'' half-space (near the ring-oxygen of the –1 glycoside), or in the ''anti'' half-space (on the opposite side of the ring-oxygen). Members of the same GH [[Families|family]] appear to share a common ''syn'' or ''anti'' [[General_acid/base|protonator]] arrangement and further, this specificity appears to be preserved within [[Clans|Clans]] of [[Families|families]]. This page's compilation of [[Sub-site nomenclature|subsite -1]] occupied complexes shows that about 70% of all GH [[Families|families]] are ''anti'' [[General_acid/base|protonators]].

Closer inspection of crystal structures of [[Sub-site nomenclature|–1/+1 subsite]]-spanning substrates, or substrate-analogue ligands, in complex with enzymes reveals a further intriguing corollary <cite>Nerinckx2005 Wu2012</cite>. In substrate-bound complexes with ''anti'' [[General_acid/base|protonating]] GH enzymes, the scissile [[Anomeric centre (alpha and beta)|anomeric bond]] (often studied using the thio-analogue) shows a dihedral angle φ (O5'-C1'-[O,S]x-Cx) that is in the lowest-energy synclinal (gauche) conformation. The rationale for this is that a minus synclinal dihedral angle φ for an equatorial glycosidic bond, or plus synclinal for an axial glycosidic bond <cite>Perez1978</cite>, allows for hyperconjugative overlap of the C1'-O5' antibonding orbital with an antiperiplanar-oriented lone pair orbital lobe of the glycosidic oxygen, thereby creating partial double bond character and stabilization of the glycosidic bond by 4–5 kcal/mol; this ground-state stabilizing phenomenon is known as the ‘exo-anomeric effect’ <cite>Cramer1997 Johnson2009 Alonso2016</cite>. ''Anti'' [[General_acid/base|protonation]] occurs on the glycosidic oxygen’s antiperiplanar lone pair, thereby removing the stabilizing exo-anomeric effect. This suggests that ''anti'' [[General_acid/base|protonation]] is an enzymic approach for lowering the activation barrier leading to the [[Transition state|transition state]] (Figure 1 centre).

''Syn'' [[General_acid/base|protonating]] [[glycoside hydrolase]]s apparently make use of a different approach <cite>Nerinckx2005 Wu2012</cite>. In many [[Sub-site nomenclature|–1/+1 subsite]]-spanning ligand complexes, the dihedral angle φ of the scissile anomeric bond has been rotated away from its lowest-energy synclinal position: clockwise to minus-anticlinal or antiperiplanar for beta-equatorial; counterclockwise to plus-anticlinal or antiperiplanar for alpha-axial [[Anomeric centre (alpha and beta)|anomeric bonds]]. This removes the hyperconjugative overlap and thus also the stabilizing exo-anomeric effect. And because of this rotation, a lone pair of the glycosidic oxygen is directed into the ''syn'' half-space, allowing it to be protonated by the ''syn''-positioned [[General_acid/base|proton donor]] (Figure 1 right).

[[File:Syn_anti.jpg|800px|thumb|center|Figure 1. Newman projections, with the glycosidic oxygen as proximal atom and the anomeric carbon as distal atom, showing ''anti'' (centre) versus ''syn'' (right) semi-lateral [[General_acid/base|protonation]] in beta-equatorial (top) and alpha-axial (bottom) [[glycoside hydrolase]]s. The indicated φ is the dihedral angle for O5'-C1'-O4-C4.]]

== Table of ''syn/anti'' protonation examples ==

This table contains only one example per GH [[Families|family]] of a ligand-complexed protein structure where the ''syn'' or ''anti'' positioning of the [[General_acid/base|proton donor]] can be clearly observed; other examples may be available on a [[Families|family-by-family]] basis. The reader is thus advised to consult the [http://www.cazy.org/fam/acc_GH.html#table CAZy database] for a current, comprehensive list of CAZyme structures. Where available, the selected examples are Michaelis-type complexes with the ligand spanning the [[Sub-site nomenclature|-1/+1 subsites]], since these have an intact glycosidic or thioglycosidic bond, or are ''N''-analogs of the substrate (''e.g.'' acarbose). In some examples, the [[General_acid/base|proton donor]] has been mutated (''e.g.'', to the corresponding amide or to an alanine), and in those cases one may wish to look at a superposition of the given PDB example with the structure of the native enzyme. If a Michaelis-type complex is not yet available, the second and third example choices, respectively, are trapped glycosyl-enzyme [[intermediate]]s and product complexes where [[Sub-site nomenclature|subsite -1]] is occupied.

''Please also be aware that this is a large table with many data. Please contact the page Author or Responsible Curator with corrections.''

=== Table ===
This table can be re-sorted by clicking on the icons in the header (''javascript must be turned on in your browser''). To reset the page to be sorted by GH family, click the ''View'' tab at the very top of the page.

{| {{Prettytable}} class="sortable"
|- valign="top"
! '''Family'''
! '''Clan'''
! '''Structure fold '''
! '''Anomeric specificity'''
! '''Mechanism'''
! '''''Syn/anti'' protonator'''
! '''Example PDB ID'''
! '''Enzyme'''
! '''Organism'''
! '''Ligand'''
! '''General acid'''
! '''Nucleophile or General base'''
! '''Reference'''
|-
| [[GH1]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2cer 2cer]
| β-glycosidase S
| ''Sulfolobus solfataricus'' P2
| phenethyl glucoimidazole
| '''Glu206'''
| Glu387
| <cite>Gloster2006</cite>
|-
| [[GH2]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vzu 2vzu]
| exo-β-glucosaminidase
| ''Amicolatopsis orientalis''
| PNP-β-{{Smallcaps|d}}-glucosamine
| '''Glu469'''
| Glu541
| <cite>van_Bueren2009</cite>
|-
| [[GH3]]
| none
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1iex 1iex]
| exo-1,3-1,4-glucanase
| ''Hordeum vulgare''
| thiocellobiose
| '''Glu491'''
| Asp285
| <cite>Hrmova2001</cite>
|-
| [[GH4]]
| none
| Rossmann + α6/β3 + β3/α4
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1u8x 1u8x]
| 6-P-α-glucosidase
| ''Bacillus subtilis''
| alpha-{{Smallcaps|d}}-glucose-6-phosphate
| '''Asp172'''
| not applicable
| <cite>Rajan2004</cite>
|-
| [[GH5]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1h2j 1h2j]
| endo-β-1,4-glucanase
| ''Bacillus agaradhaerens''
| 2',4'-DNP-2-F-cellobioside
| '''Glu129'''
| Glu228
| <cite>Varrot2003</cite>
|-
| [[GH6]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1qjw 1qjw]
| cellobiohydrolase 2
| ''Hypocrea jecorina''
| (Glc)2-S-(Glc)2
| '''Asp221'''
| debated
| <cite>Zhou1999</cite>
|-
| [[GH7]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1ovw 1ovw]
| endo-1,4-glucanase
| ''Fusarium oxysporum''
| thio-(Glc)5
| '''Glu202'''
| Glu197
| <cite>Sulzenbacher1999</cite>
|-
| [[GH8]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1kwf 1kwf]
| endo-1,4-glucanase
| ''Clostridium thermocellum''
| cellopentaose
| '''Glu95'''
| Asp278
| <cite>Guerin2002</cite>
|-
| [[GH9]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1rq5 1rq5]
| cellobiohydrolase
| ''Clostridium thermocellum''
| cellotetraose
| '''Glu795'''
| Asp383
| <cite>Schubot2004</cite>
|-
| [[GH10]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2d24 2d24]
| β-1,4-xylanase
| ''Streptomyces olivaceoviridis'' E-86
| xylopentaose
| '''Glu128'''
| Glu236
| <cite>Suzuki2009</cite>
|-
| [[GH11]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}4hk8 4hk8]
| endo-β-1,4-xylanase
| ''Hypocrea jecorina''
| xylohexaose
| '''Glu177'''
| Glu86
| <cite>Wan2014</cite>
|-
| [[GH12]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1w2u 1w2u]
| endoglucanase
| ''Humicola grisea''
| thiocellotetraose
| '''Glu205'''
| Glu120
| <cite>Sandgren2004</cite>
|-
| [[GH13]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1cxk 1cxk]
| β-cyclodextrin glucanotransferase
| ''Bacillus circulans''
| maltononaose
| '''Glu257'''
| Asp229
| <cite>Uitdehaag1999</cite>
|-
| [[GH14]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1itc 1itc]
| β-amylase
| ''Bacillus cereus''
| maltopentaose
| '''Glu172'''
| Glu367
| <cite>Miyake2003</cite>
|-
| [[GH15]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1dog 1dog]
| glucoamylase
| ''Aspergillus awamori''
| 1-deoxynojirimycin
| '''Glu179'''
| Glu400
| <cite>Harris1993</cite>
|-
| [[GH16]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1urx 1urx]
| β-agarase A
| ''Zobellia galactanivorans''
| oligoagarose
| '''Glu152'''
| Glu147
| <cite>Allouch2004</cite>
|-
| [[GH17]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzj 4gzj]
| endo-β-1,3-glucanase
| ''Solanum tuberosum''
| laminaratriose + laminarabiose
| '''Glu118'''
| Glu259
| <cite>Wojtkowiak2013</cite>
|-
| [[GH18]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1ffr 1ffr]
| chitinase A
| ''Serratia marcescens''
| (NAG)6
| '''Glu315'''
| internal
| <cite>Papanikolau2001</cite>
|-
| [[GH19]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}3wh1 3wh1]
| chitinase
| ''Bryum coronatum''
| (GlcNAc)4
| '''Glu61'''
| Glu70
| <cite>Ohnuma2014</cite>
|-
| [[GH20]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1c7s 1c7s]
| chitobiase
| ''Serratia marcescens''
| chitobiose
| '''Glu540'''
| internal
| <cite>Prag2000</cite>
|-
| [[GH22]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1h6m 1h6m]
| lysozyme C
| ''Gallus gallus''
| Chit-2-F-chitosyl
| '''Glu35'''
| Asp52
| <cite>Vocadlo2001</cite>
|-
| [[GH23]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1lsp 1lsp]
| lysozyme G
| ''Cygnus atratus''
| Bulgecin A
| '''Glu73'''
| internal
| <cite>Karlsen1996</cite>
|-
| [[GH24]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}148l 148l]
| lysozyme E
| Bacteriophage T4
| chitobiosyl
| '''Glu11'''
| Glu26
| <cite>Baldwin1993</cite>
|-
| [[GH26]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vx6 2vx6]
| exo-β-mannanase
| ''Cellvibrio japonicus'' Ueda107
| Gal1Man4
| '''Glu221'''
| Glu338
| <cite>Cartmell2008</cite>
|-
| [[GH27]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}} / beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3lrm 3lrm]
| α-galactosidase
| ''Saccharomyces cerevisiae''
| raffinose
| '''Asp209'''
| Asp141
| <cite>Fernandez-Leiro2010</cite>
|-
| [[GH28]]
| N
| β-helix
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}2uvf 2uvf]
| exo-polygalacturonosidase
| ''Yersinia enterocolitica'' ATCC9610D
| digalacturonic acid
| '''Asp402'''
| Asp381 Asp403
| <cite>Abbott2007</cite>
|-
| [[GH29]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| '''''syn'''''
| [{{PDBlink}}3uet 3uet]
| α-1,3/4-fucosidase
| ''Bifidobacterium longum'' subsp. infantis
| lacto-''N''-fucopentaose II
| '''Glu217'''
| Asp172
| <cite>Sakurama2012</cite>
|-
| [[GH30]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2y24 2y24]
| glucurono-xylanase
| ''Dickea chrysanthemi'' D1
| glucuronoxylan tetrasaccharide
| '''Glu163'''
| Glu253
| <cite>Urbanikova2011</cite>
|-
| [[GH31]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2qmj 2qmj]
| maltase-glucoamylase
| ''Homo sapiens''
| acarbose
| '''Asp542'''
| Asp443
| <cite>Sim2008</cite>
|-
| [[GH32]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2add 2add]
| fructan β-(2,1)-fructosidase
| ''Cichorium intybus''
| sucrose
| '''Glu201'''
| Asp22
| <cite>Verhaest2007</cite>
|-
| [[GH33]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1s0i 1s0i]
| transsialidase
| ''Trypanosoma cruzi''
| sialyllactose
| '''Asp59'''
| Tyr342 (with Glu230)
| <cite>Amaya2004</cite>
|-
| [[GH34]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzw 4gzw]
| N2 neuraminidase
| ''Influenza'' A Tanzania/205/2010 H3N2
| α-{{Smallcaps|d}}-Neup5Ac-(2,3)-β-{{Smallcaps|d}}-Galp-(1,4)-β-{{Smallcaps|d}}-GlcpNAc
| '''Asp151'''
| Tyr406 (with Glu277)
| <cite>Zhu2012</cite>
|-
| [[GH35]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3ogv 3ogv]
| β-galactosidase
| ''Hypocrea jecorina''
| 2-phenylethyl 1-thio-β-{{Smallcaps|d}}-galactopyranoside
| '''Glu200'''
| Glu298
| <cite>Maksimainen2011</cite>
|-
| [[GH36]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4fnu 4fnu]
| β-galactosidase
| ''Geobacillus stearothermophilus''
| stachyose
| '''Asp584'''
| Asp478
| <cite>Merceron2012</cite>
|-
| [[GH37]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2jf4 2jf4]
| trehalase
| ''Escherichia coli''
| validoxylamine
| '''Asp312'''
| Glu496
| <cite>Gibson2007</cite>
|-
| [[GH38]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3czn 3czn]
| Golgi α-mannosidase II
| ''Drosophila melanogaster''
| GlcNAcMan(5)GlcNAc(2)
| '''Asp341'''
| Asp204
| <cite>Shah2008</cite>
|-
| [[GH39]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2bfg 2bfg]
| β-xylosidase
| ''Geobacillus stearothermophilus''
| 2,5-dinitrophenyl-β-{{Smallcaps|d}}-xyloside
| '''Glu160'''
| Glu278
| <cite>Czjzek2005</cite>
|-
| [[GH42]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ucf 4ucf]
| β-galactosidase
| ''Bifidobacterium bifidum''
| {{Smallcaps|d}}-galactose
| '''Glu161'''
| Glu320
| <cite>Godoy2016</cite>
|-
| [[GH43]]
| F
| 5-fold β-propeller
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3akh 3akh]
| exo-1,5-α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces avermitilis''
| α-1,5-arabinofuranotriose
| '''Glu196'''
| Asp220
| <cite>Fujimoto2010</cite>
|-
| [[GH44]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2eqd 2eqd]
| endoglucanase
| ''Clostridium thermocellum''
| cellooctaose
| '''Glu186'''
| Glu359
| <cite>Kitago2007</cite>
|-
| [[GH45]]
| none
| 6-stranded β-barrel
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4eng 4eng]
| endo-1,4-glucanase
| ''Humicola insolens''
| cellohexaose
| '''Asp121'''
| Asp10
| <cite>Davies1996</cite>
|-
| [[GH46]]
| I
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4olt 4olt]
| chitosanase
| ''Microbacterium sp.'' OU01
| hexa-glucosamine
| '''Glu25'''
| Asp43
| <cite>Lyu2014</cite>
|-
| [[GH47]]
| none
| (α/α)7
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1x9d 1x9d]
| α-mannosidase I
| ''Homo sapiens''
| Me-2-S-(α-Man)-2-thio-α-Man
| '''Asp463'''
| Glu599
| <cite>Karaveg2005</cite>, <cite>Nerinckx2008</cite>
|-
| [[GH48]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH8''
|
|
|
|
|
|
|-
| [[GH49]]
| N
| β-helix
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH28''
|
|
|
|
|
|
|-
| [[GH50]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4bq5 4bq5]
| exo-β-agarase
| ''Saccharophagus degradans''
| neoagarotetraose
| '''Glu535'''
| Glu695
| <cite>Pluvinage2013</cite>
|-
| [[GH51]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1qw9 1qw9]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Geobacillus stearothermophilus''
| PNP-{{Smallcaps|l}}-arabinofuranoside
| '''Glu175'''
| Glu294
| <cite>Hoevel2003</cite>
|-
| [[GH52]]
| O
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| '' predicted perpendicular by clan, see at GH116''
| [{{PDBlink}}4c1p 4c1p]
| β-xylosidase
| ''Geobacillus thermoglucosidasius''
| xylobiose
| '''Asp517'''
| Glu537
| <cite>Espina2014</cite>
|-
| [[GH53]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2ccr 2ccr]
| β-1,4-galactanase
| ''Bacillus licheniformis''
| galactotriose
| '''Glu165'''
| Glu263
| <cite>Le_Nours2009</cite>
|-
| [[GH54]]
| none
| β-sandwich
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1wd4 1wd4]
| α-{{Smallcaps|l}}-arabinofuranosidase B
| ''Aspergillus kawachii''
| {{Smallcaps|l}}-arabinofuranose
| '''Asp297'''
| Glu221
| <cite>Miyanaga2004</cite>
|-
| [[GH55]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4tz5 4tz5]
| exo-β-1,3-glucanase
| ''Streptomyces sp.'' SirexAA-E
| laminarihexaose
| '''Glu502'''
| unknown
| <cite>Bianchetti2015</cite>
|-
| [[GH56]]
| none
| (β/α)7
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1fcv 1fcv]
| hyaluronidase
| ''Apis mellifera''
| (hyaluron.)4
| '''Glu113'''
| internal
| <cite>Markovic-Housley2000</cite>
|-
| [[GH57]]
| T
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1k1y 1k1y]
| glucanotransferase
| ''Thermococcus litoralis''
| acarbose
| '''Asp214'''
| Glu123
| <cite>Imamura2003</cite>
|-
| [[GH59]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ccc 4ccc]
| β-galactocerebrosidase
| ''Mus musculus''
| PNP-β-{{Smallcaps|d}}-galactoside
| '''Glu182'''
| Glu258
| <cite>Hill2013</cite>
|-
| [[GH62]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3wn0 3wn0]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces coelicolor''
| β-{{Smallcaps|l}}-Arabinofuranose
| '''Glu361'''
| Asp202
| <cite>Maehara2014</cite>
|-
| [[GH63]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5ca3 5ca3]
| α-glucosidase
| ''Escherichia coli''
| glucose and lactose
| '''Asp501'''
| Glu727
| <cite>Miyazaki2016</cite>
|-
| [[GH65]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}4ktr 4ktr]
| 2-O-α-glucosylglycerol phosphorylase
| ''Bacillus selenitireducens''
| isofagomine
| '''Glu475'''
| phosphate
| <cite>Touhara2014</cite>
|-
| [[GH66]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5axh 5axh]
| dextranase
| ''Thermoanaerobacter pseudethanolicus''
| isomaltohexaose
| '''Glu374'''
| Asp312
| <cite>Suzuki2016</cite>
|-
| [[GH67]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1l8n 1l8n]
| α-glucuronidase
| ''Geobacillus stearothermophilus''
| 4-O-methyl-{{Smallcaps|d}}-glucuronic acid and xylotriose
| '''Glu286'''
| Asp364 Glu392
| <cite>Golan2004</cite>
|-
| [[GH68]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1pt2 1pt2]
| levansucrase
| ''Bacillus subtilis''
| sucrose
| '''Glu342'''
| Asp86
| <cite>Meng2003</cite>
|-
| [[GH70]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3aic 3aic]
| glucansucrase
| ''Streptococcus mutans''
| α-acarbose
| '''Glu515'''
| Asp477
| <cite>Ito2011</cite>
|-
| [[GH72]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w62 2w62]
| β-1,3-glucanotransferase
| ''Saccharomyces cerevisiae'' S288C
| laminaripentaose
| '''Glu176'''
| Glu275
| <cite>Hurtado-Gerrero2009</cite>
|-
| [[GH74]]
| none
| 7-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}2ebs 2ebs]
| cellobiohydrolase (OXG-RCBH)
| ''Geotrichum sp.'' m128
| xyloglucan heptasaccharide
| '''Asp465'''
| Asp35
| <cite>Yaoi2007</cite>
|-
| [[GH76]]
| none
| (α/α)6
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5agd 5agd]
| endo-α-1,6-mannanase
| ''Bacillus circulans''
| α-1,6-mannopentaose
| '''Asp125'''
| Asp124
| <cite>Thompson2015</cite>
|-
| [[GH77]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2oww 2oww]
| 4-α-glucanotransferase
| ''Thermus thermofilus''
| acarbose + 4-deoxy-α-{{Smallcaps|d}}-glucose
| '''Glu340'''
| Asp293
| <cite>Barends2007</cite>
|-
| [[GH78]]
| H
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3w5n 3w5n]
| α-{{Smallcaps|l}}-rhamnosidase
| ''Streptomyces avermitilis''
| {{Smallcaps|l}}-rhamnose
| '''Glu636'''
| Glu895
| <cite>Fujimoto2013</cite>
|-
| [[GH79]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5e9c 5e9c]
| heparanase
| ''Homo sapiens''
| heparin tetrasaccharide
| '''Glu225'''
| Glu343
| <cite>Wu2015</cite>
|-
| [[GH80]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH24''
|
|
|
|
|
|
|-
| [[GH81]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5t4g 5t4g]
| endo-β-1,3-glucanase
| ''Bacillus halodurans'' C-125
| laminarin
| '''Asp466'''
| Glu542
| <cite>Pluvinage2017</cite>
|-
| [[GH83]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1z4x 1z4x]
| hemagglutinin-neuraminidase
| Simian virus 5
| α-2,3-sialyllactose
| '''Asp187''' on flexible loop
| Tyr523 (with Glu390)
| <cite>Yuan2005</cite>
|-
| [[GH84]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2chn 2chn]
| β-''N''-acetyl-glucosaminidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| NAG-thiazoline
| '''Glu242'''
| internal
| <cite>Dennis2006</cite>
|-
| [[GH85]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w92 2w92]
| endo-β-''N''-acetyl-glucosaminidase D
| ''Streptococcus pneumoniae'' TIGR4
| NAG-thiazoline
| '''Glu337'''
| internal
| <cite>Abbott2009</cite>
|-
| [[GH86]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4aw7 4aw7]
| β-porphyranase
| ''Bacteroides plebeius''
| porphyran fragment
| '''Glu152'''
| Glu279
| <cite>Hehemann_1_2012</cite>
|-
| [[GH89]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vcb 2vcb]
| α-''N''-acetyl-glucosaminidase
| ''Clostridium perfringens''
| PUGNAc
| '''Glu483'''
| Glu601
| <cite>Ficko-Blean2008</cite>
|-
| [[GH92]]
| none
| (α/α)6 and β-sandwich
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ww1 2ww1]
| α-1,2-mannosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| thiomannobioside
| '''Glu533'''
| Asp644 Asp642
| <cite>Zhu2009</cite>
|-
| [[GH93]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3a72 3a72]
| exo-arabinanase
| ''Penicillium chrysogenum''
| arabinobiose
| '''Glu246'''
| Glu174
| <cite>Sogabe2011</cite>
|-
| [[GH94]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4zli 4zli]
| cellobionic acid phosphorylase
| ''Saccharophagus degradans''
| 3-O-β-{{Smallcaps|d}}-glucopyranosyl-α-{{Smallcaps|d}}-glucopyranuronic acid
| '''Asp472'''
| phosphate
| <cite>Nam2015</cite>
|-
| [[GH95]]
| none
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ead 2ead]
| α-1,2-{{Smallcaps|l}}-fucosidase
| ''Bifidobacterium bifidum''
| Fuc-α-1,2-Gal
| '''Glu566'''
| Asn423 Asp766
| <cite>Nagae2007</cite>
|-
| [[GH97]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining + inverting
| '''''anti'''''
| [{{PDBlink}}2zq0 2zq0]
| α-glucosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| acarbose
| '''Glu532'''
| Glu508
| <cite>Kitamura2008</cite>
|-
| [[GH98]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2wmg 2wmg]
| endo-β-1,4-galactosidase
| ''Streptococcus pneumoniae''
| A-LewisY pentasaccharide
| '''Glu158'''
| Asp251 Glu301
| <cite>Higgins2009</cite>
|-
| [[GH99]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ad4 4ad4]
| endo-α-mannosidase
| ''Bacteroides xylanisolvens''
| glucose-1,3-isofagomine and α-1,2- mannobiose
| '''Glu336'''
| debated
| <cite>Thompson2012</cite>
|-
| [[GH100]]
| G
| (α/α)6 core
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5gop 5gop]
| invertase
| ''Anabaena (Nostoc) sp.'' pcc7120
| sucrose
| '''Asp188'''
| Glu414
| <cite>Xie2016</cite>
|-
| [[GH101]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5a56 5a56]
| endo-α-N-acetylgalactosaminidase
| ''Streptococcus pneumoniae'' TIGR4
| β-{{Smallcaps|d}}-Galp-(1-3)-α-{{Smallcaps|d}}-GalpNAc-(1)-methyl
| '''Glu796''' +water
| Asp764
| <cite>Gregg2015</cite>
|-
| [[GH102]]
| none
| double-ψ β-barrel
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}2pi8 2pi8]
| lytic transglycosylase A
| ''Escherichia coli''
| chitohexaose
| '''Asp308'''
| none
| <cite>van_Straaten2007</cite>
|-
| [[GH103]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1d0k 1d0k]
| lytic transglycosylase SLT35
| ''Escherichia coli''
| murodipeptides
| '''Glu162'''
| internal
| <cite>van_Asselt2000</cite>
|-
| [[GH106]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5mwk 5mwk]
| α-{{Smallcaps|l}}-rhamnosidase BT_0986
| ''Bacteroides thetaiotaomicron''
| pectin heptasaccharide
| '''Glu461'''
| Glu593 or Glu561
| <cite>Ndeh2017</cite>
|-
| [[GH107]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| ''predicted syn by clan''
| ''see at GH29''
|
|
|
|
|
|
|-
| [[GH110]]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}7jwf 7jwf]
| α-1,3-galactosidase
| ''Pseudoalteromonas distincta''
| Gal-α1,3-Gal
| '''Asp344'''
| Asp321 Asp345
| <cite>McGuire2020</cite>
|-
| [[GH113]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4cd8 4cd8]
| β-mannanase
| ''Alicyclobacillus acidocaldarius''
| mannobioimidazole
| '''Glu151'''
| Glu231
| <cite>Williams2014</cite>
|-
| [[GH116]]
| O
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''perpendicular''''' (anomaly)
| [{{PDBlink}}8i5u 8i5u]
| β-glucosidase
| ''Thermoanaerobacterium xylanolyticum'' LX-11
| laminaribiose
| '''Asp593'''
| Glu441
| <cite>Pengthaisong2023</cite>
|-
| [[GH117]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}4ak7 4ak7]
| α-1,3-3,6-anhydro-{{Smallcaps|l}}-galactosidase
| ''Bacteroides plebeius''
| neoagarobiose
| '''His302''' (relay from Asp320)
| Asp90
| <cite>Hehemann_2_2012</cite>
|-
| [[GH119]]
| T
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at GH57''
|
|
|
|
|
|
|-
| [[GH120]]
| none
| parallel β-helix and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3vsv 3vsv]
| β-xylosidase XylC
| ''Thermoanaerobacterium saccharolyticum'' JW/SL-YS485
| {{Smallcaps|d}}-xylose
| '''Glu405'''
| Asp382
| <cite>Huang2012</cite>
|-
| [[GH123]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5fr0 5fr0]
| exo-β-N-acetyl-galactosaminidase
| ''Clostridium perfringens''
| ''N''-difluoroacetyl-{{Smallcaps|d}}-galactosamine
| '''Glu345'''
| internal
| <cite>Noach2016</cite>
|-
| [[GH125]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5m7y 5m7y]
| exo-α-1,6-mannosidase
| ''Clostridium perfringens''
| 1,6-α-mannotriose
| '''Asp220'''
| Glu393
| <cite>Alonso-Gil2016</cite>
|-
| [[GH127]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3wrg 3wrg]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bifidobacterium longum''
| {{Smallcaps|l}}-arabinose
| '''Glu322'''
| Cys417
| <cite>Huang2014</cite>
|-
| [[GH128]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}6ufl 6ufl]
| β-1,3-glucanase
| ''Amycolatopsis mediterranei''
| laminarihexaose
| '''Glu102'''
| Glu199
| <cite>Santos2020</cite>
|-
| [[GH130]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5b0s 5b0s]
| β-1,2-mannobiose phosphorylase
| ''Listeria innocua''
| β-1,2-mannotriose
| '''Asp141''' relay
| phosphate
| <cite>Tsuda2015</cite>
|-
| [[GH134]]
| none
| β + α
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5jug 5jug]
| β-mannanase
| ''Streptomyces sp.''
| mannopentaose
| '''Glu45'''
| Asp57
| <cite>Jin2016</cite>
|-
| [[GH136]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}5gqf 5gqf]
| lacto-N-biosidase
| ''Bifidobacterium longum''
| lacto-N-biose
| '''Asp411'''
| Asp418
| <cite>Yamada2017</cite>
|-
| [[GH137]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|l}}
| unknown
| '''''anti'''''
| [{{PDBlink}}5mui 5mui]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0996
| ''Bacteroides thetaiotaomicron''
| pectin oligosaccharide
| '''Glu240'''
| Glu159
| <cite>Ndeh2017</cite>
|-
| [[GH138]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}6hzg 6hzg]
| α-1,2-{{Smallcaps|d}}-galacturonidase
| ''Bacteroides paurosaccharolyticus''
| alpha-{{Smallcaps|d}}-galactopyranuronic
| '''Glu294'''
| Glu361
| <cite>Labourel2019</cite>
|-
| [[GH140]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH144]]
| S
| (α/α)8
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}8xul 8xul]
| beta-1,2-glucanase
| ''Xanthomonas campestris''
| beta-1,2-glucoheptasaccharide
| '''Glu239'''
| unknown
| <cite>Nakajima2024</cite>
|-
| [[GH146]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5opj 5opj]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bacteroides thetaiotaomicron''
| {{Smallcaps|l}}-arabinose
| '''Glu320'''
| Cys416
| <cite>Luis2018</cite>
|-
| [[GH147]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH148]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH149]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH156]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}6s0e 6s0e]
| exo-α-sialidase
| uncultured bacterium pG7
| N-acetyl-2,3-dehydro-2-deoxyneuraminic acid
| '''His134''' (relay from Asp132)
| Asp14
| <cite>Bule2019</cite>
|-
| [[GH157]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH158]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH161]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH162]]
| S
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}6imw 6imw]
| endo-β-1,2-glucanase
| ''Talaromyces funiculosus''
| beta-1,2-glucan
| '''Glu262''' via C3-OH of glc at subs. +2
| Asp446
| <cite>Tanaka2019</cite>
|-
| [[GH164]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}6t75 6t75]
| β-mannosidase
| ''Bacteroides salyersiae''
| 2-deoxy-2-F-mannosyl
| '''Glu160'''
| Glu297
| <cite>Armstrong2020</cite>
|-
| [[GH167]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|-
| [[GH169]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH172]]
| none
| β-jelly roll
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}7v1w 7v1w]
| difructose-anhydride synthase
| ''Bifidobacterium dentum''
| beta-{{Smallcaps|d}}-arabinofuranose
| '''Glu270'''
| Glu291
| <cite>Kashima2021</cite>
|-
| [[GH173]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH178]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at e.g. GH15''
|
|
|
|
|
|-
| [[GH181]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}8axi 8axi]
| exo-α-sialidase
| ''Akkermansia muciniphila''
| 2-deoxy-2,3-dehydro-''N''-acetyl-neuraminic acid + T-antigen disaccharide
| '''Asp345'''
| Glu218
| <cite>Shuoker2023</cite>
|-
| [[GH183]]
| none
| 5-bladed β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}8ic1 8ic1]
| endo-α-1,5-{{Smallcaps|d}}-arabinofuranosidase
| ''Microbacterium arabinogalactanolyticum'' JCM 9171
| α-{{Smallcaps|d}}-Araf-(1,5)-α-{{Smallcaps|d}}-Araf-(1,5)-α-{{Smallcaps|d}}-Araf-(1,5)-α-{{Smallcaps|d}}-Araf
| '''Asp51'''
| Asp33
| <cite>Shimokawa2023</cite>
|-
| [[GH186]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}8ip1 8ip1]
| β-1,2-glucanase
| ''Escherechia coli''
| β-1,2-glucan
| '''Asp388'''
| Asp300 + 3 waters
| <cite>Motouchi2023</cite>
|-
| [http://www.cazy.org/GH0.html n.c.*]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2vjj 2vjj]
| endo-α-N-acetylglucosaminidase
| Bacteriophage HK620
| O18A1 O-antigen hexasaccharide
| '''Asp339'''
| Glu372
| <cite>Barbirz2008</cite>
|}
<nowiki>*</nowiki> n.c.: Found among the collection of [http://www.cazy.org/GH0.html non-classified GH sequences in the CAZy Database].

== References ==

<biblio>
# HeightmanVasella1999 Heightman TD and Vasella AT. ''Recent Insights into Inhibition, Structure, and Mechanism of Configuration-Retaining Glycosidases.'' Angew Chem Int Ed. 1999 38(6):750-770. [http://www3.interscience.wiley.com/journal/55000581/abstract Article online].
# Nerinckx2005 pmid=15642336
# Wu2012 pmid=23137336
# Perez1978 Pérez S and Marchessault RH. ''The exo-anomeric effect: experimental evidence from crystal structures.'' Carbohydr res. 1978 65:114-120. [http://dx.doi.org/10.1016/S0008-6215(00)84218-4 DOI:10.1016/S0008-6215(00)84218-4]
# Cramer1997 Cramer CJ, Truhlar DG, and French AD. ''Exo-anomeric effects on energies and geometries of different conformations of glucose and related systems in the gas phase and aqueous solution.'' Carbohydr res. 1997 298:1-14. [http://dx.doi.org/10.1016/S0008-6215(96)00297-2 DOI:10.1016/S0008-6215(96)00297-2]
# Johnson2009 pmid=19733839
# Alonso2016 pmid=26889578
# Gloster2006 pmid=17002288
# van_Bueren2009 pmid=18976664
# Hrmova2001 pmid=11709165
# Rajan2004 pmid=15341727
# Varrot2003 pmid=12595701
# Zhou1999 pmid=10508787
# Sulzenbacher1999 pmid=10200171
# Urbanikova2011 pmid=21501386
# Guerin2002 pmid=11884144
# Schubot2004 pmid=14756552
# Suzuki2009 pmid=19279191
# Wan2014 pmid=24419374
# Sandgren2004 pmid=15364577
# Uitdehaag1999 pmid=10331869
# Miyake2003 pmid=12741813
# Harris1993 pmid=8431441
# Allouch2004 pmid=15062085
# Wojtkowiak2013 pmid=23275163
# Papanikolau2001 pmid=11560481
# Prag2000 pmid=10884356
# Vocadlo2001 pmid=11518970
# Karlsen1996 pmid=15299731
# Baldwin1993 pmid=8259514
# Cartmell2008 pmid=18799462
# Fernandez-Leiro2010 pmid=20592022
# Abbott2007 pmid=17397864
# Sakurama2012 pmid=22451675
# Sim2008 pmid=18036614
# Verhaest2007 pmid=17335500
# Amaya2004 pmid=15130470
# Zhu2012 pmid=23015718
# Maksimainen2011 pmid=21130883
# Merceron2012 pmid=23012371
# Gibson2007 pmid=17455176
# Shah2008 pmid=18599462
# Czjzek2005 pmid=16212978
# Godoy2016 pmid=27685756
# Fujimoto2010 pmid=20739278
# Kitago2007 pmid=17905739
# Davies1996 pmid=15299721
# Lyu2014 pmid=24766439
# Karaveg2005 pmid=15713668
# Nerinckx2008 pmid=18619586
# Pluvinage2013 pmid=23921382
# Yuan2005 pmid=15893670
# Hoevel2003 pmid=14517232
# Espina2014 pmid=24816105
# Le_Nours2009 pmid=19089956
# Miyanaga2004 pmid=15292273
# Bianchetti2015 pmid=25752603
# Markovic-Housley2000 pmid=11080624
# Imamura2003 pmid=12618437
# Hill2013 pmid=24297913
# Maehara2014 pmid=24482228
# Miyazaki2016 pmid=27688023
# Touhara2014 pmid=24828502
# Suzuki2016 pmid=26494689
# Golan2004 pmid=14573597
# Meng2003 pmid=14517548
# Ito2011 pmid=21354427
# Hurtado-Gerrero2009 pmid=19097997
# Yaoi2007 pmid=17498741
# Thompson2015 pmid=25772148
# Barends2007 pmid=17420245
# Fujimoto2013 pmid=23486481
# Wu2015 pmid=26575439
# Pluvinage2017 pmid=28781080
# Dennis2006 pmid=16565725
# Abbott2009 pmid=19181667
# Hehemann_1_2012 pmid=23150581
# Ficko-Blean2008 pmid=18443291
# Zhu2009 pmid=20081828
# Sogabe2011 pmid=21543843
# Nam2015 pmid=26041776
# Nagae2007 pmid=17459873
# Kitamura2008 pmid=18981178
# Higgins2009 pmid=19608744
# van_Straaten2007 pmid=17502382
# van_Asselt2000 pmid=10684641
# Ndeh2017 pmid=28329766
# Labourel2019 pmid=30877196
# Nakajima2024 Nakajima M. et al. ''Extensive distribution of β-1,2-glucanases: finding of new glycoside hydrolase families of β-1,2-glucanases.'' BioRxiv preprint 2024. https://doi.org/10.1101/2024.02.06.578578
# Luis2018 pmid=29255254
# Bule2019 pmid=31645552
# Jin2016 Jin Y, Petricevic M, John A, Raich L, Jenkins H, Portela De Souza L, Cuskin F, Gilbert HJ, Rovira C, Goddard-Borger ED, Williams SJ, and Davies GJ. ''A β-Mannanase with a Lysozyme-like Fold and a Novel Molecular Catalytic Mechanism.'' ACS Cent Sci. 2016 Nov [http://dx.doi.org/10.1021/acscentsci.6b00232 DOI:10.1021/acscentsci.6b00232]
# Yamada2017 pmid=28392148
# Ohnuma2014 pmid=24582745
# Thompson2012 pmid=22219371
# Xie2016 pmid=27777307
# Gregg2015 pmid=26304114
# Williams2014 pmid=24339341

# Pengthaisong2023 pmid=37180965

# Hehemann_2_2012 pmid=22393053

# Huang2012 pmid=22992047
# Noach2016 pmid=27038508
# Alonso-Gil2016 pmid=28026180
# Huang2014 Huang CH, Zhu Z, Cheng YS, Chan HC, Ko TP, Chen CC, Wang I, Ho MR, Hsu ST, Zeng YF, Huang YN, Liu JR, Guo RT. ''Structure and Catalytic Mechanism of a Glycoside Hydrolase Family-127 β-L-Arabinofuranosidase (HypBA1).'' J Bioprocess Biotech. 2014 4:171 [http://dx.doi.org/10.4172/2155-9821.1000171 DOI:10.4172/2155-9821.1000171]
# Tsuda2015 pmid=26632508
# Barbirz2008 pmid=18547389
# Tanaka2019 pmid=30926603
# Armstrong2020 pmid=31871050
# Santos2020 pmid=32451508
# Kashima2021 pmid=34688653
# McGuire2020 pmid=33127644
# Shuoker2023 pmid=37005422
# Shimokawa2023 pmid=37726269
# Motouchi2023 pmid=37735577

</biblio>
[[Category:Definitions and explanations]]

Syn/anti lateral protonation

2025-04-03T09:35:30Z

Wim Nerinckx: GH144 syn protonator (with temporary BioRxiv2024 reference)

{{CuratorApproved}}
* [[Author]]: [[User:Wim Nerinckx|Wim Nerinckx]]
* [[Responsible Curator]]: [[User:Spencer Williams|Spencer Williams]]

----

== Overview ==

This page provides a table that summarizes the spatial positioning of the catalytic [[general acid]] residue in the active sites of [[glycoside hydrolase]]s, relative to the substrate. The table below updates those found in the seminal paper on this concept by Heightman and Vasella <cite>HeightmanVasella1999</cite>, and a following paper by Nerinckx ''et al.'' <cite>Nerinckx2005</cite>.

== Background ==

The ''"not from above, but from the side"'' concept of semi-lateral glycosidic oxygen [[General_acid/base|protonation]] by [[glycoside hydrolase]]s was introduced by Heightman and Vasella <cite>HeightmanVasella1999</cite>. It was originally only described for [[Anomeric centre (alpha and beta)|beta]]-equatorial [[glycoside hydrolase]]s, but appears to be equally applicable to enzymes acting on an [[Anomeric centre (alpha and beta)|alpha]]-axial glycosidic bond <cite>Nerinckx2005</cite>. When dividing [[Sub-site nomenclature|subsite -1]] into half-spaces by a plane defined by the glycosidic oxygen and C1' and H1' of the –1 glycoside, many ligand-complexed structures reveal that the [[General_acid/base|proton donor]] is positioned either in the ''syn'' half-space (near the ring-oxygen of the –1 glycoside), or in the ''anti'' half-space (on the opposite side of the ring-oxygen). Members of the same GH [[Families|family]] appear to share a common ''syn'' or ''anti'' [[General_acid/base|protonator]] arrangement and further, this specificity appears to be preserved within [[Clans|Clans]] of [[Families|families]]. This page's compilation of [[Sub-site nomenclature|subsite -1]] occupied complexes shows that about 70% of all GH [[Families|families]] are ''anti'' [[General_acid/base|protonators]].

Closer inspection of crystal structures of [[Sub-site nomenclature|–1/+1 subsite]]-spanning substrates, or substrate-analogue ligands, in complex with enzymes reveals a further intriguing corollary <cite>Nerinckx2005 Wu2012</cite>. In substrate-bound complexes with ''anti'' [[General_acid/base|protonating]] GH enzymes, the scissile [[Anomeric centre (alpha and beta)|anomeric bond]] (often studied using the thio-analogue) shows a dihedral angle φ (O5'-C1'-[O,S]x-Cx) that is in the lowest-energy synclinal (gauche) conformation. The rationale for this is that a minus synclinal dihedral angle φ for an equatorial glycosidic bond, or plus synclinal for an axial glycosidic bond <cite>Perez1978</cite>, allows for hyperconjugative overlap of the C1'-O5' antibonding orbital with an antiperiplanar-oriented lone pair orbital lobe of the glycosidic oxygen, thereby creating partial double bond character and stabilization of the glycosidic bond by 4–5 kcal/mol; this ground-state stabilizing phenomenon is known as the ‘exo-anomeric effect’ <cite>Cramer1997 Johnson2009 Alonso2016</cite>. ''Anti'' [[General_acid/base|protonation]] occurs on the glycosidic oxygen’s antiperiplanar lone pair, thereby removing the stabilizing exo-anomeric effect. This suggests that ''anti'' [[General_acid/base|protonation]] is an enzymic approach for lowering the activation barrier leading to the [[Transition state|transition state]] (Figure 1 centre).

''Syn'' [[General_acid/base|protonating]] [[glycoside hydrolase]]s apparently make use of a different approach <cite>Nerinckx2005 Wu2012</cite>. In many [[Sub-site nomenclature|–1/+1 subsite]]-spanning ligand complexes, the dihedral angle φ of the scissile anomeric bond has been rotated away from its lowest-energy synclinal position: clockwise to minus-anticlinal or antiperiplanar for beta-equatorial; counterclockwise to plus-anticlinal or antiperiplanar for alpha-axial [[Anomeric centre (alpha and beta)|anomeric bonds]]. This removes the hyperconjugative overlap and thus also the stabilizing exo-anomeric effect. And because of this rotation, a lone pair of the glycosidic oxygen is directed into the ''syn'' half-space, allowing it to be protonated by the ''syn''-positioned [[General_acid/base|proton donor]] (Figure 1 right).

[[File:Syn_anti.jpg|800px|thumb|center|Figure 1. Newman projections, with the glycosidic oxygen as proximal atom and the anomeric carbon as distal atom, showing ''anti'' (centre) versus ''syn'' (right) semi-lateral [[General_acid/base|protonation]] in beta-equatorial (top) and alpha-axial (bottom) [[glycoside hydrolase]]s. The indicated φ is the dihedral angle for O5'-C1'-O4-C4.]]

== Table of ''syn/anti'' protonation examples ==

This table contains only one example per GH [[Families|family]] of a ligand-complexed protein structure where the ''syn'' or ''anti'' positioning of the [[General_acid/base|proton donor]] can be clearly observed; other examples may be available on a [[Families|family-by-family]] basis. The reader is thus advised to consult the [http://www.cazy.org/fam/acc_GH.html#table CAZy database] for a current, comprehensive list of CAZyme structures. Where available, the selected examples are Michaelis-type complexes with the ligand spanning the [[Sub-site nomenclature|-1/+1 subsites]], since these have an intact glycosidic or thioglycosidic bond, or are ''N''-analogs of the substrate (''e.g.'' acarbose). In some examples, the [[General_acid/base|proton donor]] has been mutated (''e.g.'', to the corresponding amide or to an alanine), and in those cases one may wish to look at a superposition of the given PDB example with the structure of the native enzyme. If a Michaelis-type complex is not yet available, the second and third example choices, respectively, are trapped glycosyl-enzyme [[intermediate]]s and product complexes where [[Sub-site nomenclature|subsite -1]] is occupied.

''Please also be aware that this is a large table with many data. Please contact the page Author or Responsible Curator with corrections.''

=== Table ===
This table can be re-sorted by clicking on the icons in the header (''javascript must be turned on in your browser''). To reset the page to be sorted by GH family, click the ''View'' tab at the very top of the page.

{| {{Prettytable}} class="sortable"
|- valign="top"
! '''Family'''
! '''Clan'''
! '''Structure fold '''
! '''Anomeric specificity'''
! '''Mechanism'''
! '''''Syn/anti'' protonator'''
! '''Example PDB ID'''
! '''Enzyme'''
! '''Organism'''
! '''Ligand'''
! '''General acid'''
! '''Nucleophile or General base'''
! '''Reference'''
|-
| [[GH1]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2cer 2cer]
| β-glycosidase S
| ''Sulfolobus solfataricus'' P2
| phenethyl glucoimidazole
| '''Glu206'''
| Glu387
| <cite>Gloster2006</cite>
|-
| [[GH2]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vzu 2vzu]
| exo-β-glucosaminidase
| ''Amicolatopsis orientalis''
| PNP-β-{{Smallcaps|d}}-glucosamine
| '''Glu469'''
| Glu541
| <cite>van_Bueren2009</cite>
|-
| [[GH3]]
| none
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1iex 1iex]
| exo-1,3-1,4-glucanase
| ''Hordeum vulgare''
| thiocellobiose
| '''Glu491'''
| Asp285
| <cite>Hrmova2001</cite>
|-
| [[GH4]]
| none
| Rossmann + α6/β3 + β3/α4
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1u8x 1u8x]
| 6-P-α-glucosidase
| ''Bacillus subtilis''
| alpha-{{Smallcaps|d}}-glucose-6-phosphate
| '''Asp172'''
| not applicable
| <cite>Rajan2004</cite>
|-
| [[GH5]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1h2j 1h2j]
| endo-β-1,4-glucanase
| ''Bacillus agaradhaerens''
| 2',4'-DNP-2-F-cellobioside
| '''Glu129'''
| Glu228
| <cite>Varrot2003</cite>
|-
| [[GH6]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1qjw 1qjw]
| cellobiohydrolase 2
| ''Hypocrea jecorina''
| (Glc)2-S-(Glc)2
| '''Asp221'''
| debated
| <cite>Zhou1999</cite>
|-
| [[GH7]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1ovw 1ovw]
| endo-1,4-glucanase
| ''Fusarium oxysporum''
| thio-(Glc)5
| '''Glu202'''
| Glu197
| <cite>Sulzenbacher1999</cite>
|-
| [[GH8]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1kwf 1kwf]
| endo-1,4-glucanase
| ''Clostridium thermocellum''
| cellopentaose
| '''Glu95'''
| Asp278
| <cite>Guerin2002</cite>
|-
| [[GH9]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1rq5 1rq5]
| cellobiohydrolase
| ''Clostridium thermocellum''
| cellotetraose
| '''Glu795'''
| Asp383
| <cite>Schubot2004</cite>
|-
| [[GH10]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2d24 2d24]
| β-1,4-xylanase
| ''Streptomyces olivaceoviridis'' E-86
| xylopentaose
| '''Glu128'''
| Glu236
| <cite>Suzuki2009</cite>
|-
| [[GH11]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}4hk8 4hk8]
| endo-β-1,4-xylanase
| ''Hypocrea jecorina''
| xylohexaose
| '''Glu177'''
| Glu86
| <cite>Wan2014</cite>
|-
| [[GH12]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1w2u 1w2u]
| endoglucanase
| ''Humicola grisea''
| thiocellotetraose
| '''Glu205'''
| Glu120
| <cite>Sandgren2004</cite>
|-
| [[GH13]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1cxk 1cxk]
| β-cyclodextrin glucanotransferase
| ''Bacillus circulans''
| maltononaose
| '''Glu257'''
| Asp229
| <cite>Uitdehaag1999</cite>
|-
| [[GH14]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1itc 1itc]
| β-amylase
| ''Bacillus cereus''
| maltopentaose
| '''Glu172'''
| Glu367
| <cite>Miyake2003</cite>
|-
| [[GH15]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1dog 1dog]
| glucoamylase
| ''Aspergillus awamori''
| 1-deoxynojirimycin
| '''Glu179'''
| Glu400
| <cite>Harris1993</cite>
|-
| [[GH16]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1urx 1urx]
| β-agarase A
| ''Zobellia galactanivorans''
| oligoagarose
| '''Glu152'''
| Glu147
| <cite>Allouch2004</cite>
|-
| [[GH17]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzj 4gzj]
| endo-β-1,3-glucanase
| ''Solanum tuberosum''
| laminaratriose + laminarabiose
| '''Glu118'''
| Glu259
| <cite>Wojtkowiak2013</cite>
|-
| [[GH18]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1ffr 1ffr]
| chitinase A
| ''Serratia marcescens''
| (NAG)6
| '''Glu315'''
| internal
| <cite>Papanikolau2001</cite>
|-
| [[GH19]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}3wh1 3wh1]
| chitinase
| ''Bryum coronatum''
| (GlcNAc)4
| '''Glu61'''
| Glu70
| <cite>Ohnuma2014</cite>
|-
| [[GH20]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1c7s 1c7s]
| chitobiase
| ''Serratia marcescens''
| chitobiose
| '''Glu540'''
| internal
| <cite>Prag2000</cite>
|-
| [[GH22]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1h6m 1h6m]
| lysozyme C
| ''Gallus gallus''
| Chit-2-F-chitosyl
| '''Glu35'''
| Asp52
| <cite>Vocadlo2001</cite>
|-
| [[GH23]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1lsp 1lsp]
| lysozyme G
| ''Cygnus atratus''
| Bulgecin A
| '''Glu73'''
| internal
| <cite>Karlsen1996</cite>
|-
| [[GH24]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}148l 148l]
| lysozyme E
| Bacteriophage T4
| chitobiosyl
| '''Glu11'''
| Glu26
| <cite>Baldwin1993</cite>
|-
| [[GH26]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vx6 2vx6]
| exo-β-mannanase
| ''Cellvibrio japonicus'' Ueda107
| Gal1Man4
| '''Glu221'''
| Glu338
| <cite>Cartmell2008</cite>
|-
| [[GH27]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}} / beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3lrm 3lrm]
| α-galactosidase
| ''Saccharomyces cerevisiae''
| raffinose
| '''Asp209'''
| Asp141
| <cite>Fernandez-Leiro2010</cite>
|-
| [[GH28]]
| N
| β-helix
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}2uvf 2uvf]
| exo-polygalacturonosidase
| ''Yersinia enterocolitica'' ATCC9610D
| digalacturonic acid
| '''Asp402'''
| Asp381 Asp403
| <cite>Abbott2007</cite>
|-
| [[GH29]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| '''''syn'''''
| [{{PDBlink}}3uet 3uet]
| α-1,3/4-fucosidase
| ''Bifidobacterium longum'' subsp. infantis
| lacto-''N''-fucopentaose II
| '''Glu217'''
| Asp172
| <cite>Sakurama2012</cite>
|-
| [[GH30]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2y24 2y24]
| glucurono-xylanase
| ''Dickea chrysanthemi'' D1
| glucuronoxylan tetrasaccharide
| '''Glu163'''
| Glu253
| <cite>Urbanikova2011</cite>
|-
| [[GH31]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2qmj 2qmj]
| maltase-glucoamylase
| ''Homo sapiens''
| acarbose
| '''Asp542'''
| Asp443
| <cite>Sim2008</cite>
|-
| [[GH32]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2add 2add]
| fructan β-(2,1)-fructosidase
| ''Cichorium intybus''
| sucrose
| '''Glu201'''
| Asp22
| <cite>Verhaest2007</cite>
|-
| [[GH33]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1s0i 1s0i]
| transsialidase
| ''Trypanosoma cruzi''
| sialyllactose
| '''Asp59'''
| Tyr342 (with Glu230)
| <cite>Amaya2004</cite>
|-
| [[GH34]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzw 4gzw]
| N2 neuraminidase
| ''Influenza'' A Tanzania/205/2010 H3N2
| α-{{Smallcaps|d}}-Neup5Ac-(2,3)-β-{{Smallcaps|d}}-Galp-(1,4)-β-{{Smallcaps|d}}-GlcpNAc
| '''Asp151'''
| Tyr406 (with Glu277)
| <cite>Zhu2012</cite>
|-
| [[GH35]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3ogv 3ogv]
| β-galactosidase
| ''Hypocrea jecorina''
| 2-phenylethyl 1-thio-β-{{Smallcaps|d}}-galactopyranoside
| '''Glu200'''
| Glu298
| <cite>Maksimainen2011</cite>
|-
| [[GH36]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4fnu 4fnu]
| β-galactosidase
| ''Geobacillus stearothermophilus''
| stachyose
| '''Asp584'''
| Asp478
| <cite>Merceron2012</cite>
|-
| [[GH37]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2jf4 2jf4]
| trehalase
| ''Escherichia coli''
| validoxylamine
| '''Asp312'''
| Glu496
| <cite>Gibson2007</cite>
|-
| [[GH38]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3czn 3czn]
| Golgi α-mannosidase II
| ''Drosophila melanogaster''
| GlcNAcMan(5)GlcNAc(2)
| '''Asp341'''
| Asp204
| <cite>Shah2008</cite>
|-
| [[GH39]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2bfg 2bfg]
| β-xylosidase
| ''Geobacillus stearothermophilus''
| 2,5-dinitrophenyl-β-{{Smallcaps|d}}-xyloside
| '''Glu160'''
| Glu278
| <cite>Czjzek2005</cite>
|-
| [[GH42]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ucf 4ucf]
| β-galactosidase
| ''Bifidobacterium bifidum''
| {{Smallcaps|d}}-galactose
| '''Glu161'''
| Glu320
| <cite>Godoy2016</cite>
|-
| [[GH43]]
| F
| 5-fold β-propeller
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3akh 3akh]
| exo-1,5-α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces avermitilis''
| α-1,5-arabinofuranotriose
| '''Glu196'''
| Asp220
| <cite>Fujimoto2010</cite>
|-
| [[GH44]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2eqd 2eqd]
| endoglucanase
| ''Clostridium thermocellum''
| cellooctaose
| '''Glu186'''
| Glu359
| <cite>Kitago2007</cite>
|-
| [[GH45]]
| none
| 6-stranded β-barrel
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4eng 4eng]
| endo-1,4-glucanase
| ''Humicola insolens''
| cellohexaose
| '''Asp121'''
| Asp10
| <cite>Davies1996</cite>
|-
| [[GH46]]
| I
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4olt 4olt]
| chitosanase
| ''Microbacterium sp.'' OU01
| hexa-glucosamine
| '''Glu25'''
| Asp43
| <cite>Lyu2014</cite>
|-
| [[GH47]]
| none
| (α/α)7
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1x9d 1x9d]
| α-mannosidase I
| ''Homo sapiens''
| Me-2-S-(α-Man)-2-thio-α-Man
| '''Asp463'''
| Glu599
| <cite>Karaveg2005</cite>, <cite>Nerinckx2008</cite>
|-
| [[GH48]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH8''
|
|
|
|
|
|
|-
| [[GH49]]
| N
| β-helix
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH28''
|
|
|
|
|
|
|-
| [[GH50]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4bq5 4bq5]
| exo-β-agarase
| ''Saccharophagus degradans''
| neoagarotetraose
| '''Glu535'''
| Glu695
| <cite>Pluvinage2013</cite>
|-
| [[GH51]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1qw9 1qw9]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Geobacillus stearothermophilus''
| PNP-{{Smallcaps|l}}-arabinofuranoside
| '''Glu175'''
| Glu294
| <cite>Hoevel2003</cite>
|-
| [[GH52]]
| O
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4c1p 4c1p]
| β-xylosidase
| ''Geobacillus thermoglucosidasius''
| xylobiose
| '''Asp517'''
| Glu537
| <cite>Espina2014</cite>
|-
| [[GH53]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2ccr 2ccr]
| β-1,4-galactanase
| ''Bacillus licheniformis''
| galactotriose
| '''Glu165'''
| Glu263
| <cite>Le_Nours2009</cite>
|-
| [[GH54]]
| none
| β-sandwich
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1wd4 1wd4]
| α-{{Smallcaps|l}}-arabinofuranosidase B
| ''Aspergillus kawachii''
| {{Smallcaps|l}}-arabinofuranose
| '''Asp297'''
| Glu221
| <cite>Miyanaga2004</cite>
|-
| [[GH55]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4tz5 4tz5]
| exo-β-1,3-glucanase
| ''Streptomyces sp.'' SirexAA-E
| laminarihexaose
| '''Glu502'''
| unknown
| <cite>Bianchetti2015</cite>
|-
| [[GH56]]
| none
| (β/α)7
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1fcv 1fcv]
| hyaluronidase
| ''Apis mellifera''
| (hyaluron.)4
| '''Glu113'''
| internal
| <cite>Markovic-Housley2000</cite>
|-
| [[GH57]]
| T
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1k1y 1k1y]
| glucanotransferase
| ''Thermococcus litoralis''
| acarbose
| '''Asp214'''
| Glu123
| <cite>Imamura2003</cite>
|-
| [[GH59]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ccc 4ccc]
| β-galactocerebrosidase
| ''Mus musculus''
| PNP-β-{{Smallcaps|d}}-galactoside
| '''Glu182'''
| Glu258
| <cite>Hill2013</cite>
|-
| [[GH62]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3wn0 3wn0]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces coelicolor''
| β-{{Smallcaps|l}}-Arabinofuranose
| '''Glu361'''
| Asp202
| <cite>Maehara2014</cite>
|-
| [[GH63]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5ca3 5ca3]
| α-glucosidase
| ''Escherichia coli''
| glucose and lactose
| '''Asp501'''
| Glu727
| <cite>Miyazaki2016</cite>
|-
| [[GH65]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}4ktr 4ktr]
| 2-O-α-glucosylglycerol phosphorylase
| ''Bacillus selenitireducens''
| isofagomine
| '''Glu475'''
| phosphate
| <cite>Touhara2014</cite>
|-
| [[GH66]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5axh 5axh]
| dextranase
| ''Thermoanaerobacter pseudethanolicus''
| isomaltohexaose
| '''Glu374'''
| Asp312
| <cite>Suzuki2016</cite>
|-
| [[GH67]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1l8n 1l8n]
| α-glucuronidase
| ''Geobacillus stearothermophilus''
| 4-O-methyl-{{Smallcaps|d}}-glucuronic acid and xylotriose
| '''Glu286'''
| Asp364 Glu392
| <cite>Golan2004</cite>
|-
| [[GH68]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1pt2 1pt2]
| levansucrase
| ''Bacillus subtilis''
| sucrose
| '''Glu342'''
| Asp86
| <cite>Meng2003</cite>
|-
| [[GH70]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3aic 3aic]
| glucansucrase
| ''Streptococcus mutans''
| α-acarbose
| '''Glu515'''
| Asp477
| <cite>Ito2011</cite>
|-
| [[GH72]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w62 2w62]
| β-1,3-glucanotransferase
| ''Saccharomyces cerevisiae'' S288C
| laminaripentaose
| '''Glu176'''
| Glu275
| <cite>Hurtado-Gerrero2009</cite>
|-
| [[GH74]]
| none
| 7-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}2ebs 2ebs]
| cellobiohydrolase (OXG-RCBH)
| ''Geotrichum sp.'' m128
| xyloglucan heptasaccharide
| '''Asp465'''
| Asp35
| <cite>Yaoi2007</cite>
|-
| [[GH76]]
| none
| (α/α)6
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5agd 5agd]
| endo-α-1,6-mannanase
| ''Bacillus circulans''
| α-1,6-mannopentaose
| '''Asp125'''
| Asp124
| <cite>Thompson2015</cite>
|-
| [[GH77]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2oww 2oww]
| 4-α-glucanotransferase
| ''Thermus thermofilus''
| acarbose + 4-deoxy-α-{{Smallcaps|d}}-glucose
| '''Glu340'''
| Asp293
| <cite>Barends2007</cite>
|-
| [[GH78]]
| H
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3w5n 3w5n]
| α-{{Smallcaps|l}}-rhamnosidase
| ''Streptomyces avermitilis''
| {{Smallcaps|l}}-rhamnose
| '''Glu636'''
| Glu895
| <cite>Fujimoto2013</cite>
|-
| [[GH79]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5e9c 5e9c]
| heparanase
| ''Homo sapiens''
| heparin tetrasaccharide
| '''Glu225'''
| Glu343
| <cite>Wu2015</cite>
|-
| [[GH80]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH24''
|
|
|
|
|
|
|-
| [[GH81]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5t4g 5t4g]
| endo-β-1,3-glucanase
| ''Bacillus halodurans'' C-125
| laminarin
| '''Asp466'''
| Glu542
| <cite>Pluvinage2017</cite>
|-
| [[GH83]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1z4x 1z4x]
| hemagglutinin-neuraminidase
| Simian virus 5
| α-2,3-sialyllactose
| '''Asp187''' on flexible loop
| Tyr523 (with Glu390)
| <cite>Yuan2005</cite>
|-
| [[GH84]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2chn 2chn]
| β-''N''-acetyl-glucosaminidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| NAG-thiazoline
| '''Glu242'''
| internal
| <cite>Dennis2006</cite>
|-
| [[GH85]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w92 2w92]
| endo-β-''N''-acetyl-glucosaminidase D
| ''Streptococcus pneumoniae'' TIGR4
| NAG-thiazoline
| '''Glu337'''
| internal
| <cite>Abbott2009</cite>
|-
| [[GH86]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4aw7 4aw7]
| β-porphyranase
| ''Bacteroides plebeius''
| porphyran fragment
| '''Glu152'''
| Glu279
| <cite>Hehemann_1_2012</cite>
|-
| [[GH89]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vcb 2vcb]
| α-''N''-acetyl-glucosaminidase
| ''Clostridium perfringens''
| PUGNAc
| '''Glu483'''
| Glu601
| <cite>Ficko-Blean2008</cite>
|-
| [[GH92]]
| none
| (α/α)6 and β-sandwich
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ww1 2ww1]
| α-1,2-mannosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| thiomannobioside
| '''Glu533'''
| Asp644 Asp642
| <cite>Zhu2009</cite>
|-
| [[GH93]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3a72 3a72]
| exo-arabinanase
| ''Penicillium chrysogenum''
| arabinobiose
| '''Glu246'''
| Glu174
| <cite>Sogabe2011</cite>
|-
| [[GH94]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4zli 4zli]
| cellobionic acid phosphorylase
| ''Saccharophagus degradans''
| 3-O-β-{{Smallcaps|d}}-glucopyranosyl-α-{{Smallcaps|d}}-glucopyranuronic acid
| '''Asp472'''
| phosphate
| <cite>Nam2015</cite>
|-
| [[GH95]]
| none
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ead 2ead]
| α-1,2-{{Smallcaps|l}}-fucosidase
| ''Bifidobacterium bifidum''
| Fuc-α-1,2-Gal
| '''Glu566'''
| Asn423 Asp766
| <cite>Nagae2007</cite>
|-
| [[GH97]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining + inverting
| '''''anti'''''
| [{{PDBlink}}2zq0 2zq0]
| α-glucosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| acarbose
| '''Glu532'''
| Glu508
| <cite>Kitamura2008</cite>
|-
| [[GH98]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2wmg 2wmg]
| endo-β-1,4-galactosidase
| ''Streptococcus pneumoniae''
| A-LewisY pentasaccharide
| '''Glu158'''
| Asp251 Glu301
| <cite>Higgins2009</cite>
|-
| [[GH99]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ad4 4ad4]
| endo-α-mannosidase
| ''Bacteroides xylanisolvens''
| glucose-1,3-isofagomine and α-1,2- mannobiose
| '''Glu336'''
| debated
| <cite>Thompson2012</cite>
|-
| [[GH100]]
| G
| (α/α)6 core
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5gop 5gop]
| invertase
| ''Anabaena (Nostoc) sp.'' pcc7120
| sucrose
| '''Asp188'''
| Glu414
| <cite>Xie2016</cite>
|-
| [[GH101]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5a56 5a56]
| endo-α-N-acetylgalactosaminidase
| ''Streptococcus pneumoniae'' TIGR4
| β-{{Smallcaps|d}}-Galp-(1-3)-α-{{Smallcaps|d}}-GalpNAc-(1)-methyl
| '''Glu796''' +water
| Asp764
| <cite>Gregg2015</cite>
|-
| [[GH102]]
| none
| double-ψ β-barrel
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}2pi8 2pi8]
| lytic transglycosylase A
| ''Escherichia coli''
| chitohexaose
| '''Asp308'''
| none
| <cite>van_Straaten2007</cite>
|-
| [[GH103]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1d0k 1d0k]
| lytic transglycosylase SLT35
| ''Escherichia coli''
| murodipeptides
| '''Glu162'''
| internal
| <cite>van_Asselt2000</cite>
|-
| [[GH106]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5mwk 5mwk]
| α-{{Smallcaps|l}}-rhamnosidase BT_0986
| ''Bacteroides thetaiotaomicron''
| pectin heptasaccharide
| '''Glu461'''
| Glu593 or Glu561
| <cite>Ndeh2017</cite>
|-
| [[GH107]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| ''predicted syn by clan''
| ''see at GH29''
|
|
|
|
|
|
|-
| [[GH110]]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}7jwf 7jwf]
| α-1,3-galactosidase
| ''Pseudoalteromonas distincta''
| Gal-α1,3-Gal
| '''Asp344'''
| Asp321 Asp345
| <cite>McGuire2020</cite>
|-
| [[GH113]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4cd8 4cd8]
| β-mannanase
| ''Alicyclobacillus acidocaldarius''
| mannobioimidazole
| '''Glu151'''
| Glu231
| <cite>Williams2014</cite>
|-
| [[GH116]]
| O
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at GH52''
|
|
|
|
|
|
|-
| [[GH117]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}4ak7 4ak7]
| α-1,3-3,6-anhydro-{{Smallcaps|l}}-galactosidase
| ''Bacteroides plebeius''
| neoagarobiose
| '''His302''' (relay from Asp320)
| Asp90
| <cite>Hehemann_2_2012</cite>
|-
| [[GH119]]
| T
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at GH57''
|
|
|
|
|
|
|-
| [[GH120]]
| none
| parallel β-helix and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3vsv 3vsv]
| β-xylosidase XylC
| ''Thermoanaerobacterium saccharolyticum'' JW/SL-YS485
| {{Smallcaps|d}}-xylose
| '''Glu405'''
| Asp382
| <cite>Huang2012</cite>
|-
| [[GH123]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5fr0 5fr0]
| exo-β-N-acetyl-galactosaminidase
| ''Clostridium perfringens''
| ''N''-difluoroacetyl-{{Smallcaps|d}}-galactosamine
| '''Glu345'''
| internal
| <cite>Noach2016</cite>
|-
| [[GH125]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5m7y 5m7y]
| exo-α-1,6-mannosidase
| ''Clostridium perfringens''
| 1,6-α-mannotriose
| '''Asp220'''
| Glu393
| <cite>Alonso-Gil2016</cite>
|-
| [[GH127]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3wrg 3wrg]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bifidobacterium longum''
| {{Smallcaps|l}}-arabinose
| '''Glu322'''
| Cys417
| <cite>Huang2014</cite>
|-
| [[GH128]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}6ufl 6ufl]
| β-1,3-glucanase
| ''Amycolatopsis mediterranei''
| laminarihexaose
| '''Glu102'''
| Glu199
| <cite>Santos2020</cite>
|-
| [[GH130]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5b0s 5b0s]
| β-1,2-mannobiose phosphorylase
| ''Listeria innocua''
| β-1,2-mannotriose
| '''Asp141''' relay
| phosphate
| <cite>Tsuda2015</cite>
|-
| [[GH134]]
| none
| β + α
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5jug 5jug]
| β-mannanase
| ''Streptomyces sp.''
| mannopentaose
| '''Glu45'''
| Asp57
| <cite>Jin2016</cite>
|-
| [[GH136]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}5gqf 5gqf]
| lacto-N-biosidase
| ''Bifidobacterium longum''
| lacto-N-biose
| '''Asp411'''
| Asp418
| <cite>Yamada2017</cite>
|-
| [[GH137]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|l}}
| unknown
| '''''anti'''''
| [{{PDBlink}}5mui 5mui]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0996
| ''Bacteroides thetaiotaomicron''
| pectin oligosaccharide
| '''Glu240'''
| Glu159
| <cite>Ndeh2017</cite>
|-
| [[GH138]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}6hzg 6hzg]
| α-1,2-{{Smallcaps|d}}-galacturonidase
| ''Bacteroides paurosaccharolyticus''
| alpha-{{Smallcaps|d}}-galactopyranuronic
| '''Glu294'''
| Glu361
| <cite>Labourel2019</cite>
|-
| [[GH140]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH144]]
| S
| (α/α)8
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}8xul 8xul]
| beta-1,2-glucanase
| ''Xanthomonas campestris''
| beta-1,2-glucoheptasaccharide
| '''Glu239'''
| unknown
| <cite>Nakajima2024</cite>
|-
| [[GH146]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5opj 5opj]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bacteroides thetaiotaomicron''
| {{Smallcaps|l}}-arabinose
| '''Glu320'''
| Cys416
| <cite>Luis2018</cite>
|-
| [[GH147]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH148]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH149]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH156]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}6s0e 6s0e]
| exo-α-sialidase
| uncultured bacterium pG7
| N-acetyl-2,3-dehydro-2-deoxyneuraminic acid
| '''His134''' (relay from Asp132)
| Asp14
| <cite>Bule2019</cite>
|-
| [[GH157]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH158]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH161]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH162]]
| S
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}6imw 6imw]
| endo-β-1,2-glucanase
| ''Talaromyces funiculosus''
| beta-1,2-glucan
| '''Glu262''' via C3-OH of glc at subs. +2
| Asp446
| <cite>Tanaka2019</cite>
|-
| [[GH164]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}6t75 6t75]
| β-mannosidase
| ''Bacteroides salyersiae''
| 2-deoxy-2-F-mannosyl
| '''Glu160'''
| Glu297
| <cite>Armstrong2020</cite>
|-
| [[GH167]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|-
| [[GH169]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH172]]
| none
| β-jelly roll
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}7v1w 7v1w]
| difructose-anhydride synthase
| ''Bifidobacterium dentum''
| beta-{{Smallcaps|d}}-arabinofuranose
| '''Glu270'''
| Glu291
| <cite>Kashima2021</cite>
|-
| [[GH173]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH178]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at e.g. GH15''
|
|
|
|
|
|-
| [[GH181]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}8axi 8axi]
| exo-α-sialidase
| ''Akkermansia muciniphila''
| 2-deoxy-2,3-dehydro-''N''-acetyl-neuraminic acid + T-antigen disaccharide
| '''Asp345'''
| Glu218
| <cite>Shuoker2023</cite>
|-
| [[GH183]]
| none
| 5-bladed β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}8ic1 8ic1]
| endo-α-1,5-{{Smallcaps|d}}-arabinofuranosidase
| ''Microbacterium arabinogalactanolyticum'' JCM 9171
| α-{{Smallcaps|d}}-Araf-(1,5)-α-{{Smallcaps|d}}-Araf-(1,5)-α-{{Smallcaps|d}}-Araf-(1,5)-α-{{Smallcaps|d}}-Araf
| '''Asp51'''
| Asp33
| <cite>Shimokawa2023</cite>
|-
| [[GH186]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}8ip1 8ip1]
| β-1,2-glucanase
| ''Escherechia coli''
| β-1,2-glucan
| '''Asp388'''
| Asp300 + 3 waters
| <cite>Motouchi2023</cite>
|-
| [http://www.cazy.org/GH0.html n.c.*]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2vjj 2vjj]
| endo-α-N-acetylglucosaminidase
| Bacteriophage HK620
| O18A1 O-antigen hexasaccharide
| '''Asp339'''
| Glu372
| <cite>Barbirz2008</cite>
|}
<nowiki>*</nowiki> n.c.: Found among the collection of [http://www.cazy.org/GH0.html non-classified GH sequences in the CAZy Database].

== References ==

<biblio>
# HeightmanVasella1999 Heightman TD and Vasella AT. ''Recent Insights into Inhibition, Structure, and Mechanism of Configuration-Retaining Glycosidases.'' Angew Chem Int Ed. 1999 38(6):750-770. [http://www3.interscience.wiley.com/journal/55000581/abstract Article online].
# Nerinckx2005 pmid=15642336
# Wu2012 pmid=23137336
# Perez1978 Pérez S and Marchessault RH. ''The exo-anomeric effect: experimental evidence from crystal structures.'' Carbohydr res. 1978 65:114-120. [http://dx.doi.org/10.1016/S0008-6215(00)84218-4 DOI:10.1016/S0008-6215(00)84218-4]
# Cramer1997 Cramer CJ, Truhlar DG, and French AD. ''Exo-anomeric effects on energies and geometries of different conformations of glucose and related systems in the gas phase and aqueous solution.'' Carbohydr res. 1997 298:1-14. [http://dx.doi.org/10.1016/S0008-6215(96)00297-2 DOI:10.1016/S0008-6215(96)00297-2]
# Johnson2009 pmid=19733839
# Alonso2016 pmid=26889578
# Gloster2006 pmid=17002288
# van_Bueren2009 pmid=18976664
# Hrmova2001 pmid=11709165
# Rajan2004 pmid=15341727
# Varrot2003 pmid=12595701
# Zhou1999 pmid=10508787
# Sulzenbacher1999 pmid=10200171
# Urbanikova2011 pmid=21501386
# Guerin2002 pmid=11884144
# Schubot2004 pmid=14756552
# Suzuki2009 pmid=19279191
# Wan2014 pmid=24419374
# Sandgren2004 pmid=15364577
# Uitdehaag1999 pmid=10331869
# Miyake2003 pmid=12741813
# Harris1993 pmid=8431441
# Allouch2004 pmid=15062085
# Wojtkowiak2013 pmid=23275163
# Papanikolau2001 pmid=11560481
# Prag2000 pmid=10884356
# Vocadlo2001 pmid=11518970
# Karlsen1996 pmid=15299731
# Baldwin1993 pmid=8259514
# Cartmell2008 pmid=18799462
# Fernandez-Leiro2010 pmid=20592022
# Abbott2007 pmid=17397864
# Sakurama2012 pmid=22451675
# Sim2008 pmid=18036614
# Verhaest2007 pmid=17335500
# Amaya2004 pmid=15130470
# Zhu2012 pmid=23015718
# Maksimainen2011 pmid=21130883
# Merceron2012 pmid=23012371
# Gibson2007 pmid=17455176
# Shah2008 pmid=18599462
# Czjzek2005 pmid=16212978
# Godoy2016 pmid=27685756
# Fujimoto2010 pmid=20739278
# Kitago2007 pmid=17905739
# Davies1996 pmid=15299721
# Lyu2014 pmid=24766439
# Karaveg2005 pmid=15713668
# Nerinckx2008 pmid=18619586
# Pluvinage2013 pmid=23921382
# Yuan2005 pmid=15893670
# Hoevel2003 pmid=14517232
# Espina2014 pmid=24816105
# Le_Nours2009 pmid=19089956
# Miyanaga2004 pmid=15292273
# Bianchetti2015 pmid=25752603
# Markovic-Housley2000 pmid=11080624
# Imamura2003 pmid=12618437
# Hill2013 pmid=24297913
# Maehara2014 pmid=24482228
# Miyazaki2016 pmid=27688023
# Touhara2014 pmid=24828502
# Suzuki2016 pmid=26494689
# Golan2004 pmid=14573597
# Meng2003 pmid=14517548
# Ito2011 pmid=21354427
# Hurtado-Gerrero2009 pmid=19097997
# Yaoi2007 pmid=17498741
# Thompson2015 pmid=25772148
# Barends2007 pmid=17420245
# Fujimoto2013 pmid=23486481
# Wu2015 pmid=26575439
# Pluvinage2017 pmid=28781080
# Dennis2006 pmid=16565725
# Abbott2009 pmid=19181667
# Hehemann_1_2012 pmid=23150581
# Ficko-Blean2008 pmid=18443291
# Zhu2009 pmid=20081828
# Sogabe2011 pmid=21543843
# Nam2015 pmid=26041776
# Nagae2007 pmid=17459873
# Kitamura2008 pmid=18981178
# Higgins2009 pmid=19608744
# van_Straaten2007 pmid=17502382
# van_Asselt2000 pmid=10684641
# Ndeh2017 pmid=28329766
# Labourel2019 pmid=30877196
# Nakajima2024 Nakajima M. et al. ''Extensive distribution of β-1,2-glucanases: finding of new glycoside hydrolase families of β-1,2-glucanases.'' BioRxiv preprint 2024. https://doi.org/10.1101/2024.02.06.578578
# Luis2018 pmid=29255254
# Bule2019 pmid=31645552
# Jin2016 Jin Y, Petricevic M, John A, Raich L, Jenkins H, Portela De Souza L, Cuskin F, Gilbert HJ, Rovira C, Goddard-Borger ED, Williams SJ, and Davies GJ. ''A β-Mannanase with a Lysozyme-like Fold and a Novel Molecular Catalytic Mechanism.'' ACS Cent Sci. 2016 Nov [http://dx.doi.org/10.1021/acscentsci.6b00232 DOI:10.1021/acscentsci.6b00232]
# Yamada2017 pmid=28392148
# Ohnuma2014 pmid=24582745
# Thompson2012 pmid=22219371
# Xie2016 pmid=27777307
# Gregg2015 pmid=26304114
# Williams2014 pmid=24339341
# Hehemann_2_2012 pmid=22393053
# Huang2012 pmid=22992047
# Noach2016 pmid=27038508
# Alonso-Gil2016 pmid=28026180
# Huang2014 Huang CH, Zhu Z, Cheng YS, Chan HC, Ko TP, Chen CC, Wang I, Ho MR, Hsu ST, Zeng YF, Huang YN, Liu JR, Guo RT. ''Structure and Catalytic Mechanism of a Glycoside Hydrolase Family-127 β-L-Arabinofuranosidase (HypBA1).'' J Bioprocess Biotech. 2014 4:171 [http://dx.doi.org/10.4172/2155-9821.1000171 DOI:10.4172/2155-9821.1000171]
# Tsuda2015 pmid=26632508
# Barbirz2008 pmid=18547389
# Tanaka2019 pmid=30926603
# Armstrong2020 pmid=31871050
# Santos2020 pmid=32451508
# Kashima2021 pmid=34688653
# McGuire2020 pmid=33127644
# Shuoker2023 pmid=37005422
# Shimokawa2023 pmid=37726269
# Motouchi2023 pmid=37735577

</biblio>
[[Category:Definitions and explanations]]

Syn/anti lateral protonation

2025-04-03T08:07:24Z

Wim Nerinckx: Correction at GH83 after re-check with its pub and reviewing 3D-examples from Clan-E's GH33 and GH34

{{CuratorApproved}}
* [[Author]]: [[User:Wim Nerinckx|Wim Nerinckx]]
* [[Responsible Curator]]: [[User:Spencer Williams|Spencer Williams]]

----

== Overview ==

This page provides a table that summarizes the spatial positioning of the catalytic [[general acid]] residue in the active sites of [[glycoside hydrolase]]s, relative to the substrate. The table below updates those found in the seminal paper on this concept by Heightman and Vasella <cite>HeightmanVasella1999</cite>, and a following paper by Nerinckx ''et al.'' <cite>Nerinckx2005</cite>.

== Background ==

The ''"not from above, but from the side"'' concept of semi-lateral glycosidic oxygen [[General_acid/base|protonation]] by [[glycoside hydrolase]]s was introduced by Heightman and Vasella <cite>HeightmanVasella1999</cite>. It was originally only described for [[Anomeric centre (alpha and beta)|beta]]-equatorial [[glycoside hydrolase]]s, but appears to be equally applicable to enzymes acting on an [[Anomeric centre (alpha and beta)|alpha]]-axial glycosidic bond <cite>Nerinckx2005</cite>. When dividing [[Sub-site nomenclature|subsite -1]] into half-spaces by a plane defined by the glycosidic oxygen and C1' and H1' of the –1 glycoside, many ligand-complexed structures reveal that the [[General_acid/base|proton donor]] is positioned either in the ''syn'' half-space (near the ring-oxygen of the –1 glycoside), or in the ''anti'' half-space (on the opposite side of the ring-oxygen). Members of the same GH [[Families|family]] appear to share a common ''syn'' or ''anti'' [[General_acid/base|protonator]] arrangement and further, this specificity appears to be preserved within [[Clans|Clans]] of [[Families|families]]. This page's compilation of [[Sub-site nomenclature|subsite -1]] occupied complexes shows that about 70% of all GH [[Families|families]] are ''anti'' [[General_acid/base|protonators]].

Closer inspection of crystal structures of [[Sub-site nomenclature|–1/+1 subsite]]-spanning substrates, or substrate-analogue ligands, in complex with enzymes reveals a further intriguing corollary <cite>Nerinckx2005 Wu2012</cite>. In substrate-bound complexes with ''anti'' [[General_acid/base|protonating]] GH enzymes, the scissile [[Anomeric centre (alpha and beta)|anomeric bond]] (often studied using the thio-analogue) shows a dihedral angle φ (O5'-C1'-[O,S]x-Cx) that is in the lowest-energy synclinal (gauche) conformation. The rationale for this is that a minus synclinal dihedral angle φ for an equatorial glycosidic bond, or plus synclinal for an axial glycosidic bond <cite>Perez1978</cite>, allows for hyperconjugative overlap of the C1'-O5' antibonding orbital with an antiperiplanar-oriented lone pair orbital lobe of the glycosidic oxygen, thereby creating partial double bond character and stabilization of the glycosidic bond by 4–5 kcal/mol; this ground-state stabilizing phenomenon is known as the ‘exo-anomeric effect’ <cite>Cramer1997 Johnson2009 Alonso2016</cite>. ''Anti'' [[General_acid/base|protonation]] occurs on the glycosidic oxygen’s antiperiplanar lone pair, thereby removing the stabilizing exo-anomeric effect. This suggests that ''anti'' [[General_acid/base|protonation]] is an enzymic approach for lowering the activation barrier leading to the [[Transition state|transition state]] (Figure 1 centre).

''Syn'' [[General_acid/base|protonating]] [[glycoside hydrolase]]s apparently make use of a different approach <cite>Nerinckx2005 Wu2012</cite>. In many [[Sub-site nomenclature|–1/+1 subsite]]-spanning ligand complexes, the dihedral angle φ of the scissile anomeric bond has been rotated away from its lowest-energy synclinal position: clockwise to minus-anticlinal or antiperiplanar for beta-equatorial; counterclockwise to plus-anticlinal or antiperiplanar for alpha-axial [[Anomeric centre (alpha and beta)|anomeric bonds]]. This removes the hyperconjugative overlap and thus also the stabilizing exo-anomeric effect. And because of this rotation, a lone pair of the glycosidic oxygen is directed into the ''syn'' half-space, allowing it to be protonated by the ''syn''-positioned [[General_acid/base|proton donor]] (Figure 1 right).

[[File:Syn_anti.jpg|800px|thumb|center|Figure 1. Newman projections, with the glycosidic oxygen as proximal atom and the anomeric carbon as distal atom, showing ''anti'' (centre) versus ''syn'' (right) semi-lateral [[General_acid/base|protonation]] in beta-equatorial (top) and alpha-axial (bottom) [[glycoside hydrolase]]s. The indicated φ is the dihedral angle for O5'-C1'-O4-C4.]]

== Table of ''syn/anti'' protonation examples ==

This table contains only one example per GH [[Families|family]] of a ligand-complexed protein structure where the ''syn'' or ''anti'' positioning of the [[General_acid/base|proton donor]] can be clearly observed; other examples may be available on a [[Families|family-by-family]] basis. The reader is thus advised to consult the [http://www.cazy.org/fam/acc_GH.html#table CAZy database] for a current, comprehensive list of CAZyme structures. Where available, the selected examples are Michaelis-type complexes with the ligand spanning the [[Sub-site nomenclature|-1/+1 subsites]], since these have an intact glycosidic or thioglycosidic bond, or are ''N''-analogs of the substrate (''e.g.'' acarbose). In some examples, the [[General_acid/base|proton donor]] has been mutated (''e.g.'', to the corresponding amide or to an alanine), and in those cases one may wish to look at a superposition of the given PDB example with the structure of the native enzyme. If a Michaelis-type complex is not yet available, the second and third example choices, respectively, are trapped glycosyl-enzyme [[intermediate]]s and product complexes where [[Sub-site nomenclature|subsite -1]] is occupied.

''Please also be aware that this is a large table with many data. Please contact the page Author or Responsible Curator with corrections.''

=== Table ===
This table can be re-sorted by clicking on the icons in the header (''javascript must be turned on in your browser''). To reset the page to be sorted by GH family, click the ''View'' tab at the very top of the page.

{| {{Prettytable}} class="sortable"
|- valign="top"
! '''Family'''
! '''Clan'''
! '''Structure fold '''
! '''Anomeric specificity'''
! '''Mechanism'''
! '''''Syn/anti'' protonator'''
! '''Example PDB ID'''
! '''Enzyme'''
! '''Organism'''
! '''Ligand'''
! '''General acid'''
! '''Nucleophile or General base'''
! '''Reference'''
|-
| [[GH1]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2cer 2cer]
| β-glycosidase S
| ''Sulfolobus solfataricus'' P2
| phenethyl glucoimidazole
| '''Glu206'''
| Glu387
| <cite>Gloster2006</cite>
|-
| [[GH2]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vzu 2vzu]
| exo-β-glucosaminidase
| ''Amicolatopsis orientalis''
| PNP-β-{{Smallcaps|d}}-glucosamine
| '''Glu469'''
| Glu541
| <cite>van_Bueren2009</cite>
|-
| [[GH3]]
| none
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1iex 1iex]
| exo-1,3-1,4-glucanase
| ''Hordeum vulgare''
| thiocellobiose
| '''Glu491'''
| Asp285
| <cite>Hrmova2001</cite>
|-
| [[GH4]]
| none
| Rossmann + α6/β3 + β3/α4
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1u8x 1u8x]
| 6-P-α-glucosidase
| ''Bacillus subtilis''
| alpha-{{Smallcaps|d}}-glucose-6-phosphate
| '''Asp172'''
| not applicable
| <cite>Rajan2004</cite>
|-
| [[GH5]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1h2j 1h2j]
| endo-β-1,4-glucanase
| ''Bacillus agaradhaerens''
| 2',4'-DNP-2-F-cellobioside
| '''Glu129'''
| Glu228
| <cite>Varrot2003</cite>
|-
| [[GH6]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1qjw 1qjw]
| cellobiohydrolase 2
| ''Hypocrea jecorina''
| (Glc)2-S-(Glc)2
| '''Asp221'''
| debated
| <cite>Zhou1999</cite>
|-
| [[GH7]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1ovw 1ovw]
| endo-1,4-glucanase
| ''Fusarium oxysporum''
| thio-(Glc)5
| '''Glu202'''
| Glu197
| <cite>Sulzenbacher1999</cite>
|-
| [[GH8]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1kwf 1kwf]
| endo-1,4-glucanase
| ''Clostridium thermocellum''
| cellopentaose
| '''Glu95'''
| Asp278
| <cite>Guerin2002</cite>
|-
| [[GH9]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1rq5 1rq5]
| cellobiohydrolase
| ''Clostridium thermocellum''
| cellotetraose
| '''Glu795'''
| Asp383
| <cite>Schubot2004</cite>
|-
| [[GH10]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2d24 2d24]
| β-1,4-xylanase
| ''Streptomyces olivaceoviridis'' E-86
| xylopentaose
| '''Glu128'''
| Glu236
| <cite>Suzuki2009</cite>
|-
| [[GH11]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}4hk8 4hk8]
| endo-β-1,4-xylanase
| ''Hypocrea jecorina''
| xylohexaose
| '''Glu177'''
| Glu86
| <cite>Wan2014</cite>
|-
| [[GH12]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1w2u 1w2u]
| endoglucanase
| ''Humicola grisea''
| thiocellotetraose
| '''Glu205'''
| Glu120
| <cite>Sandgren2004</cite>
|-
| [[GH13]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1cxk 1cxk]
| β-cyclodextrin glucanotransferase
| ''Bacillus circulans''
| maltononaose
| '''Glu257'''
| Asp229
| <cite>Uitdehaag1999</cite>
|-
| [[GH14]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1itc 1itc]
| β-amylase
| ''Bacillus cereus''
| maltopentaose
| '''Glu172'''
| Glu367
| <cite>Miyake2003</cite>
|-
| [[GH15]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1dog 1dog]
| glucoamylase
| ''Aspergillus awamori''
| 1-deoxynojirimycin
| '''Glu179'''
| Glu400
| <cite>Harris1993</cite>
|-
| [[GH16]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1urx 1urx]
| β-agarase A
| ''Zobellia galactanivorans''
| oligoagarose
| '''Glu152'''
| Glu147
| <cite>Allouch2004</cite>
|-
| [[GH17]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzj 4gzj]
| endo-β-1,3-glucanase
| ''Solanum tuberosum''
| laminaratriose + laminarabiose
| '''Glu118'''
| Glu259
| <cite>Wojtkowiak2013</cite>
|-
| [[GH18]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1ffr 1ffr]
| chitinase A
| ''Serratia marcescens''
| (NAG)6
| '''Glu315'''
| internal
| <cite>Papanikolau2001</cite>
|-
| [[GH19]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}3wh1 3wh1]
| chitinase
| ''Bryum coronatum''
| (GlcNAc)4
| '''Glu61'''
| Glu70
| <cite>Ohnuma2014</cite>
|-
| [[GH20]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1c7s 1c7s]
| chitobiase
| ''Serratia marcescens''
| chitobiose
| '''Glu540'''
| internal
| <cite>Prag2000</cite>
|-
| [[GH22]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1h6m 1h6m]
| lysozyme C
| ''Gallus gallus''
| Chit-2-F-chitosyl
| '''Glu35'''
| Asp52
| <cite>Vocadlo2001</cite>
|-
| [[GH23]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1lsp 1lsp]
| lysozyme G
| ''Cygnus atratus''
| Bulgecin A
| '''Glu73'''
| internal
| <cite>Karlsen1996</cite>
|-
| [[GH24]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}148l 148l]
| lysozyme E
| Bacteriophage T4
| chitobiosyl
| '''Glu11'''
| Glu26
| <cite>Baldwin1993</cite>
|-
| [[GH26]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vx6 2vx6]
| exo-β-mannanase
| ''Cellvibrio japonicus'' Ueda107
| Gal1Man4
| '''Glu221'''
| Glu338
| <cite>Cartmell2008</cite>
|-
| [[GH27]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}} / beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3lrm 3lrm]
| α-galactosidase
| ''Saccharomyces cerevisiae''
| raffinose
| '''Asp209'''
| Asp141
| <cite>Fernandez-Leiro2010</cite>
|-
| [[GH28]]
| N
| β-helix
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}2uvf 2uvf]
| exo-polygalacturonosidase
| ''Yersinia enterocolitica'' ATCC9610D
| digalacturonic acid
| '''Asp402'''
| Asp381 Asp403
| <cite>Abbott2007</cite>
|-
| [[GH29]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| '''''syn'''''
| [{{PDBlink}}3uet 3uet]
| α-1,3/4-fucosidase
| ''Bifidobacterium longum'' subsp. infantis
| lacto-''N''-fucopentaose II
| '''Glu217'''
| Asp172
| <cite>Sakurama2012</cite>
|-
| [[GH30]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2y24 2y24]
| glucurono-xylanase
| ''Dickea chrysanthemi'' D1
| glucuronoxylan tetrasaccharide
| '''Glu163'''
| Glu253
| <cite>Urbanikova2011</cite>
|-
| [[GH31]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2qmj 2qmj]
| maltase-glucoamylase
| ''Homo sapiens''
| acarbose
| '''Asp542'''
| Asp443
| <cite>Sim2008</cite>
|-
| [[GH32]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2add 2add]
| fructan β-(2,1)-fructosidase
| ''Cichorium intybus''
| sucrose
| '''Glu201'''
| Asp22
| <cite>Verhaest2007</cite>
|-
| [[GH33]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1s0i 1s0i]
| transsialidase
| ''Trypanosoma cruzi''
| sialyllactose
| '''Asp59'''
| Tyr342 (with Glu230)
| <cite>Amaya2004</cite>
|-
| [[GH34]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzw 4gzw]
| N2 neuraminidase
| ''Influenza'' A Tanzania/205/2010 H3N2
| α-{{Smallcaps|d}}-Neup5Ac-(2,3)-β-{{Smallcaps|d}}-Galp-(1,4)-β-{{Smallcaps|d}}-GlcpNAc
| '''Asp151'''
| Tyr406 (with Glu277)
| <cite>Zhu2012</cite>
|-
| [[GH35]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3ogv 3ogv]
| β-galactosidase
| ''Hypocrea jecorina''
| 2-phenylethyl 1-thio-β-{{Smallcaps|d}}-galactopyranoside
| '''Glu200'''
| Glu298
| <cite>Maksimainen2011</cite>
|-
| [[GH36]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4fnu 4fnu]
| β-galactosidase
| ''Geobacillus stearothermophilus''
| stachyose
| '''Asp584'''
| Asp478
| <cite>Merceron2012</cite>
|-
| [[GH37]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2jf4 2jf4]
| trehalase
| ''Escherichia coli''
| validoxylamine
| '''Asp312'''
| Glu496
| <cite>Gibson2007</cite>
|-
| [[GH38]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3czn 3czn]
| Golgi α-mannosidase II
| ''Drosophila melanogaster''
| GlcNAcMan(5)GlcNAc(2)
| '''Asp341'''
| Asp204
| <cite>Shah2008</cite>
|-
| [[GH39]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2bfg 2bfg]
| β-xylosidase
| ''Geobacillus stearothermophilus''
| 2,5-dinitrophenyl-β-{{Smallcaps|d}}-xyloside
| '''Glu160'''
| Glu278
| <cite>Czjzek2005</cite>
|-
| [[GH42]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ucf 4ucf]
| β-galactosidase
| ''Bifidobacterium bifidum''
| {{Smallcaps|d}}-galactose
| '''Glu161'''
| Glu320
| <cite>Godoy2016</cite>
|-
| [[GH43]]
| F
| 5-fold β-propeller
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3akh 3akh]
| exo-1,5-α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces avermitilis''
| α-1,5-arabinofuranotriose
| '''Glu196'''
| Asp220
| <cite>Fujimoto2010</cite>
|-
| [[GH44]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2eqd 2eqd]
| endoglucanase
| ''Clostridium thermocellum''
| cellooctaose
| '''Glu186'''
| Glu359
| <cite>Kitago2007</cite>
|-
| [[GH45]]
| none
| 6-stranded β-barrel
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4eng 4eng]
| endo-1,4-glucanase
| ''Humicola insolens''
| cellohexaose
| '''Asp121'''
| Asp10
| <cite>Davies1996</cite>
|-
| [[GH46]]
| I
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4olt 4olt]
| chitosanase
| ''Microbacterium sp.'' OU01
| hexa-glucosamine
| '''Glu25'''
| Asp43
| <cite>Lyu2014</cite>
|-
| [[GH47]]
| none
| (α/α)7
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1x9d 1x9d]
| α-mannosidase I
| ''Homo sapiens''
| Me-2-S-(α-Man)-2-thio-α-Man
| '''Asp463'''
| Glu599
| <cite>Karaveg2005</cite>, <cite>Nerinckx2008</cite>
|-
| [[GH48]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH8''
|
|
|
|
|
|
|-
| [[GH49]]
| N
| β-helix
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH28''
|
|
|
|
|
|
|-
| [[GH50]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4bq5 4bq5]
| exo-β-agarase
| ''Saccharophagus degradans''
| neoagarotetraose
| '''Glu535'''
| Glu695
| <cite>Pluvinage2013</cite>
|-
| [[GH51]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1qw9 1qw9]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Geobacillus stearothermophilus''
| PNP-{{Smallcaps|l}}-arabinofuranoside
| '''Glu175'''
| Glu294
| <cite>Hoevel2003</cite>
|-
| [[GH52]]
| O
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4c1p 4c1p]
| β-xylosidase
| ''Geobacillus thermoglucosidasius''
| xylobiose
| '''Asp517'''
| Glu537
| <cite>Espina2014</cite>
|-
| [[GH53]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2ccr 2ccr]
| β-1,4-galactanase
| ''Bacillus licheniformis''
| galactotriose
| '''Glu165'''
| Glu263
| <cite>Le_Nours2009</cite>
|-
| [[GH54]]
| none
| β-sandwich
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1wd4 1wd4]
| α-{{Smallcaps|l}}-arabinofuranosidase B
| ''Aspergillus kawachii''
| {{Smallcaps|l}}-arabinofuranose
| '''Asp297'''
| Glu221
| <cite>Miyanaga2004</cite>
|-
| [[GH55]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4tz5 4tz5]
| exo-β-1,3-glucanase
| ''Streptomyces sp.'' SirexAA-E
| laminarihexaose
| '''Glu502'''
| unknown
| <cite>Bianchetti2015</cite>
|-
| [[GH56]]
| none
| (β/α)7
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1fcv 1fcv]
| hyaluronidase
| ''Apis mellifera''
| (hyaluron.)4
| '''Glu113'''
| internal
| <cite>Markovic-Housley2000</cite>
|-
| [[GH57]]
| T
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1k1y 1k1y]
| glucanotransferase
| ''Thermococcus litoralis''
| acarbose
| '''Asp214'''
| Glu123
| <cite>Imamura2003</cite>
|-
| [[GH59]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ccc 4ccc]
| β-galactocerebrosidase
| ''Mus musculus''
| PNP-β-{{Smallcaps|d}}-galactoside
| '''Glu182'''
| Glu258
| <cite>Hill2013</cite>
|-
| [[GH62]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3wn0 3wn0]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces coelicolor''
| β-{{Smallcaps|l}}-Arabinofuranose
| '''Glu361'''
| Asp202
| <cite>Maehara2014</cite>
|-
| [[GH63]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5ca3 5ca3]
| α-glucosidase
| ''Escherichia coli''
| glucose and lactose
| '''Asp501'''
| Glu727
| <cite>Miyazaki2016</cite>
|-
| [[GH65]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}4ktr 4ktr]
| 2-O-α-glucosylglycerol phosphorylase
| ''Bacillus selenitireducens''
| isofagomine
| '''Glu475'''
| phosphate
| <cite>Touhara2014</cite>
|-
| [[GH66]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5axh 5axh]
| dextranase
| ''Thermoanaerobacter pseudethanolicus''
| isomaltohexaose
| '''Glu374'''
| Asp312
| <cite>Suzuki2016</cite>
|-
| [[GH67]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1l8n 1l8n]
| α-glucuronidase
| ''Geobacillus stearothermophilus''
| 4-O-methyl-{{Smallcaps|d}}-glucuronic acid and xylotriose
| '''Glu286'''
| Asp364 Glu392
| <cite>Golan2004</cite>
|-
| [[GH68]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1pt2 1pt2]
| levansucrase
| ''Bacillus subtilis''
| sucrose
| '''Glu342'''
| Asp86
| <cite>Meng2003</cite>
|-
| [[GH70]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3aic 3aic]
| glucansucrase
| ''Streptococcus mutans''
| α-acarbose
| '''Glu515'''
| Asp477
| <cite>Ito2011</cite>
|-
| [[GH72]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w62 2w62]
| β-1,3-glucanotransferase
| ''Saccharomyces cerevisiae'' S288C
| laminaripentaose
| '''Glu176'''
| Glu275
| <cite>Hurtado-Gerrero2009</cite>
|-
| [[GH74]]
| none
| 7-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}2ebs 2ebs]
| cellobiohydrolase (OXG-RCBH)
| ''Geotrichum sp.'' m128
| xyloglucan heptasaccharide
| '''Asp465'''
| Asp35
| <cite>Yaoi2007</cite>
|-
| [[GH76]]
| none
| (α/α)6
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5agd 5agd]
| endo-α-1,6-mannanase
| ''Bacillus circulans''
| α-1,6-mannopentaose
| '''Asp125'''
| Asp124
| <cite>Thompson2015</cite>
|-
| [[GH77]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2oww 2oww]
| 4-α-glucanotransferase
| ''Thermus thermofilus''
| acarbose + 4-deoxy-α-{{Smallcaps|d}}-glucose
| '''Glu340'''
| Asp293
| <cite>Barends2007</cite>
|-
| [[GH78]]
| H
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3w5n 3w5n]
| α-{{Smallcaps|l}}-rhamnosidase
| ''Streptomyces avermitilis''
| {{Smallcaps|l}}-rhamnose
| '''Glu636'''
| Glu895
| <cite>Fujimoto2013</cite>
|-
| [[GH79]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5e9c 5e9c]
| heparanase
| ''Homo sapiens''
| heparin tetrasaccharide
| '''Glu225'''
| Glu343
| <cite>Wu2015</cite>
|-
| [[GH80]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH24''
|
|
|
|
|
|
|-
| [[GH81]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5t4g 5t4g]
| endo-β-1,3-glucanase
| ''Bacillus halodurans'' C-125
| laminarin
| '''Asp466'''
| Glu542
| <cite>Pluvinage2017</cite>
|-
| [[GH83]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1z4x 1z4x]
| hemagglutinin-neuraminidase
| Simian virus 5
| α-2,3-sialyllactose
| '''Asp187''' on flexible loop
| Tyr523 (with Glu390)
| <cite>Yuan2005</cite>
|-
| [[GH84]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2chn 2chn]
| β-''N''-acetyl-glucosaminidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| NAG-thiazoline
| '''Glu242'''
| internal
| <cite>Dennis2006</cite>
|-
| [[GH85]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w92 2w92]
| endo-β-''N''-acetyl-glucosaminidase D
| ''Streptococcus pneumoniae'' TIGR4
| NAG-thiazoline
| '''Glu337'''
| internal
| <cite>Abbott2009</cite>
|-
| [[GH86]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4aw7 4aw7]
| β-porphyranase
| ''Bacteroides plebeius''
| porphyran fragment
| '''Glu152'''
| Glu279
| <cite>Hehemann_1_2012</cite>
|-
| [[GH89]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vcb 2vcb]
| α-''N''-acetyl-glucosaminidase
| ''Clostridium perfringens''
| PUGNAc
| '''Glu483'''
| Glu601
| <cite>Ficko-Blean2008</cite>
|-
| [[GH92]]
| none
| (α/α)6 and β-sandwich
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ww1 2ww1]
| α-1,2-mannosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| thiomannobioside
| '''Glu533'''
| Asp644 Asp642
| <cite>Zhu2009</cite>
|-
| [[GH93]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3a72 3a72]
| exo-arabinanase
| ''Penicillium chrysogenum''
| arabinobiose
| '''Glu246'''
| Glu174
| <cite>Sogabe2011</cite>
|-
| [[GH94]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4zli 4zli]
| cellobionic acid phosphorylase
| ''Saccharophagus degradans''
| 3-O-β-{{Smallcaps|d}}-glucopyranosyl-α-{{Smallcaps|d}}-glucopyranuronic acid
| '''Asp472'''
| phosphate
| <cite>Nam2015</cite>
|-
| [[GH95]]
| none
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ead 2ead]
| α-1,2-{{Smallcaps|l}}-fucosidase
| ''Bifidobacterium bifidum''
| Fuc-α-1,2-Gal
| '''Glu566'''
| Asn423 Asp766
| <cite>Nagae2007</cite>
|-
| [[GH97]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining + inverting
| '''''anti'''''
| [{{PDBlink}}2zq0 2zq0]
| α-glucosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| acarbose
| '''Glu532'''
| Glu508
| <cite>Kitamura2008</cite>
|-
| [[GH98]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2wmg 2wmg]
| endo-β-1,4-galactosidase
| ''Streptococcus pneumoniae''
| A-LewisY pentasaccharide
| '''Glu158'''
| Asp251 Glu301
| <cite>Higgins2009</cite>
|-
| [[GH99]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ad4 4ad4]
| endo-α-mannosidase
| ''Bacteroides xylanisolvens''
| glucose-1,3-isofagomine and α-1,2- mannobiose
| '''Glu336'''
| debated
| <cite>Thompson2012</cite>
|-
| [[GH100]]
| G
| (α/α)6 core
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5gop 5gop]
| invertase
| ''Anabaena (Nostoc) sp.'' pcc7120
| sucrose
| '''Asp188'''
| Glu414
| <cite>Xie2016</cite>

|-
| [[GH101]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5a56 5a56]
| endo-α-N-acetylgalactosaminidase
| ''Streptococcus pneumoniae'' TIGR4
| β-{{Smallcaps|d}}-Galp-(1-3)-α-{{Smallcaps|d}}-GalpNAc-(1)-methyl
| '''Glu796''' +water
| Asp764

| <cite>Gregg2015</cite>

|-

| [[GH102]]
| none
| double-ψ β-barrel
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}2pi8 2pi8]
| lytic transglycosylase A
| ''Escherichia coli''
| chitohexaose
| '''Asp308'''
| none
| <cite>van_Straaten2007</cite>
|-
| [[GH103]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1d0k 1d0k]
| lytic transglycosylase SLT35
| ''Escherichia coli''
| murodipeptides
| '''Glu162'''
| internal
| <cite>van_Asselt2000</cite>
|-
| [[GH106]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5mwk 5mwk]
| α-{{Smallcaps|l}}-rhamnosidase BT_0986
| ''Bacteroides thetaiotaomicron''
| pectin heptasaccharide
| '''Glu461'''
| Glu593 or Glu561
| <cite>Ndeh2017</cite>
|-
| [[GH107]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| ''predicted syn by clan''
| ''see at GH29''
|
|
|
|
|
|
|-
| [[GH110]]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}7jwf 7jwf]
| α-1,3-galactosidase
| ''Pseudoalteromonas distincta''
| Gal-α1,3-Gal
| '''Asp344'''
| Asp321 Asp345
| <cite>McGuire2020</cite>
|-
| [[GH113]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4cd8 4cd8]
| β-mannanase
| ''Alicyclobacillus acidocaldarius''
| mannobioimidazole
| '''Glu151'''
| Glu231
| <cite>Williams2014</cite>
|-
| [[GH116]]
| O
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at GH52''
|
|
|
|
|
|
|-
| [[GH117]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}4ak7 4ak7]
| α-1,3-3,6-anhydro-{{Smallcaps|l}}-galactosidase
| ''Bacteroides plebeius''
| neoagarobiose
| '''His302''' (relay from Asp320)
| Asp90
| <cite>Hehemann_2_2012</cite>
|-
| [[GH119]]
| T
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at GH57''
|
|
|
|
|
|
|-
| [[GH120]]
| none
| parallel β-helix and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3vsv 3vsv]
| β-xylosidase XylC
| ''Thermoanaerobacterium saccharolyticum'' JW/SL-YS485
| {{Smallcaps|d}}-xylose
| '''Glu405'''
| Asp382
| <cite>Huang2012</cite>
|-
| [[GH123]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5fr0 5fr0]
| exo-β-N-acetyl-galactosaminidase
| ''Clostridium perfringens''
| ''N''-difluoroacetyl-{{Smallcaps|d}}-galactosamine
| '''Glu345'''
| internal
| <cite>Noach2016</cite>
|-
| [[GH125]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5m7y 5m7y]
| exo-α-1,6-mannosidase
| ''Clostridium perfringens''
| 1,6-α-mannotriose
| '''Asp220'''
| Glu393
| <cite>Alonso-Gil2016</cite>
|-
| [[GH127]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3wrg 3wrg]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bifidobacterium longum''
| {{Smallcaps|l}}-arabinose
| '''Glu322'''
| Cys417
| <cite>Huang2014</cite>
|-
| [[GH128]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}6ufl 6ufl]
| β-1,3-glucanase
| ''Amycolatopsis mediterranei''
| laminarihexaose
| '''Glu102'''
| Glu199
| <cite>Santos2020</cite>
|-
| [[GH130]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5b0s 5b0s]
| β-1,2-mannobiose phosphorylase
| ''Listeria innocua''
| β-1,2-mannotriose
| '''Asp141''' relay
| phosphate
| <cite>Tsuda2015</cite>
|-
| [[GH134]]
| none
| β + α
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5jug 5jug]
| β-mannanase
| ''Streptomyces sp.''
| mannopentaose
| '''Glu45'''
| Asp57
| <cite>Jin2016</cite>
|-
| [[GH136]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}5gqf 5gqf]
| lacto-N-biosidase
| ''Bifidobacterium longum''
| lacto-N-biose
| '''Asp411'''
| Asp418
| <cite>Yamada2017</cite>
|-
| [[GH137]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|l}}
| unknown
| '''''anti'''''
| [{{PDBlink}}5mui 5mui]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0996
| ''Bacteroides thetaiotaomicron''
| pectin oligosaccharide
| '''Glu240'''
| Glu159
| <cite>Ndeh2017</cite>
|-
| [[GH138]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}6hzg 6hzg]
| α-1,2-{{Smallcaps|d}}-galacturonidase
| ''Bacteroides paurosaccharolyticus''
| alpha-{{Smallcaps|d}}-galactopyranuronic
| '''Glu294'''
| Glu361
| <cite>Labourel2019</cite>
|-
| [[GH140]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH146]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5opj 5opj]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0349
| ''Bacteroides thetaiotaomicron''
| {{Smallcaps|l}}-arabinose
| '''Glu320'''
| Cys416
| <cite>Luis2018</cite>
|-
| [[GH147]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH148]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH149]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH156]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}6s0e 6s0e]
| exo-α-sialidase
| uncultured bacterium pG7
| N-acetyl-2,3-dehydro-2-deoxyneuraminic acid
| '''His134''' (relay from Asp132)
| Asp14
| <cite>Bule2019</cite>
|-
| [[GH157]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH158]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH161]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH162]]
| S
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}6imw 6imw]
| endo-β-1,2-glucanase
| ''Talaromyces funiculosus''
| beta-1,2-glucan
| '''Glu262''' via C3-OH of glc at subs. +2
| Asp446
| <cite>Tanaka2019</cite>
|-
| [[GH164]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}6t75 6t75]
| β-mannosidase
| ''Bacteroides salyersiae''
| 2-deoxy-2-F-mannosyl
| '''Glu160'''
| Glu297
| <cite>Armstrong2020</cite>
|-
| [[GH167]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|-
| [[GH169]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH172]]
| none
| β-jelly roll
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}7v1w 7v1w]
| difructose-anhydride synthase
| ''Bifidobacterium dentum''
| beta-{{Smallcaps|d}}-arabinofuranose
| '''Glu270'''
| Glu291
| <cite>Kashima2021</cite>
|-
| [[GH173]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH178]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at e.g. GH15''
|
|
|
|

|
|-
| [[GH181]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}8axi 8axi]
| exo-α-sialidase
| ''Akkermansia muciniphila''
| 2-deoxy-2,3-dehydro-''N''-acetyl-neuraminic acid + T-antigen disaccharide
| '''Asp345'''
| Glu218
| <cite>Shuoker2023</cite>
|-
| [[GH183]]
| none
| 5-bladed β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}8ic1 8ic1]
| endo-α-1,5-{{Smallcaps|d}}-arabinofuranosidase
| ''Microbacterium arabinogalactanolyticum'' JCM 9171
| α-{{Smallcaps|d}}-Araf-(1,5)-α-{{Smallcaps|d}}-Araf-(1,5)-α-{{Smallcaps|d}}-Araf-(1,5)-α-{{Smallcaps|d}}-Araf
| '''Asp51'''
| Asp33
| <cite>Shimokawa2023</cite>
|-
| [[GH186]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}8ip1 8ip1]
| β-1,2-glucanase
| ''Escherechia coli''
| β-1,2-glucan
| '''Asp388'''
| Asp300 + 3 waters
| <cite>Motouchi2023</cite>
|-
| [http://www.cazy.org/GH0.html n.c.*]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2vjj 2vjj]
| endo-α-N-acetylglucosaminidase
| Bacteriophage HK620
| O18A1 O-antigen hexasaccharide
| '''Asp339'''
| Glu372
| <cite>Barbirz2008</cite>
|}
<nowiki>*</nowiki> n.c.: Found among the collection of [http://www.cazy.org/GH0.html non-classified GH sequences in the CAZy Database].

== References ==

<biblio>
# HeightmanVasella1999 Heightman TD and Vasella AT. ''Recent Insights into Inhibition, Structure, and Mechanism of Configuration-Retaining Glycosidases.'' Angew Chem Int Ed. 1999 38(6):750-770. [http://www3.interscience.wiley.com/journal/55000581/abstract Article online].
# Nerinckx2005 pmid=15642336
# Wu2012 pmid=23137336
# Perez1978 Pérez S and Marchessault RH. ''The exo-anomeric effect: experimental evidence from crystal structures.'' Carbohydr res. 1978 65:114-120. [http://dx.doi.org/10.1016/S0008-6215(00)84218-4 DOI:10.1016/S0008-6215(00)84218-4]
# Cramer1997 Cramer CJ, Truhlar DG, and French AD. ''Exo-anomeric effects on energies and geometries of different conformations of glucose and related systems in the gas phase and aqueous solution.'' Carbohydr res. 1997 298:1-14. [http://dx.doi.org/10.1016/S0008-6215(96)00297-2 DOI:10.1016/S0008-6215(96)00297-2]
# Johnson2009 pmid=19733839
# Alonso2016 pmid=26889578
# Gloster2006 pmid=17002288
# van_Bueren2009 pmid=18976664
# Hrmova2001 pmid=11709165
# Rajan2004 pmid=15341727
# Varrot2003 pmid=12595701
# Zhou1999 pmid=10508787
# Sulzenbacher1999 pmid=10200171
# Urbanikova2011 pmid=21501386
# Guerin2002 pmid=11884144
# Schubot2004 pmid=14756552
# Suzuki2009 pmid=19279191
# Wan2014 pmid=24419374
# Sandgren2004 pmid=15364577
# Uitdehaag1999 pmid=10331869
# Miyake2003 pmid=12741813
# Harris1993 pmid=8431441
# Allouch2004 pmid=15062085
# Wojtkowiak2013 pmid=23275163
# Papanikolau2001 pmid=11560481
# Prag2000 pmid=10884356
# Vocadlo2001 pmid=11518970
# Karlsen1996 pmid=15299731
# Baldwin1993 pmid=8259514
# Cartmell2008 pmid=18799462
# Fernandez-Leiro2010 pmid=20592022
# Abbott2007 pmid=17397864
# Sakurama2012 pmid=22451675
# Sim2008 pmid=18036614
# Verhaest2007 pmid=17335500
# Amaya2004 pmid=15130470
# Zhu2012 pmid=23015718
# Maksimainen2011 pmid=21130883
# Merceron2012 pmid=23012371
# Gibson2007 pmid=17455176
# Shah2008 pmid=18599462
# Czjzek2005 pmid=16212978
# Godoy2016 pmid=27685756
# Fujimoto2010 pmid=20739278
# Kitago2007 pmid=17905739
# Davies1996 pmid=15299721
# Lyu2014 pmid=24766439
# Karaveg2005 pmid=15713668
# Nerinckx2008 pmid=18619586
# Pluvinage2013 pmid=23921382
# Yuan2005 pmid=15893670
# Hoevel2003 pmid=14517232
# Espina2014 pmid=24816105
# Le_Nours2009 pmid=19089956
# Miyanaga2004 pmid=15292273
# Bianchetti2015 pmid=25752603
# Markovic-Housley2000 pmid=11080624
# Imamura2003 pmid=12618437
# Hill2013 pmid=24297913
# Maehara2014 pmid=24482228
# Miyazaki2016 pmid=27688023
# Touhara2014 pmid=24828502
# Suzuki2016 pmid=26494689
# Golan2004 pmid=14573597
# Meng2003 pmid=14517548
# Ito2011 pmid=21354427
# Hurtado-Gerrero2009 pmid=19097997
# Yaoi2007 pmid=17498741
# Thompson2015 pmid=25772148
# Barends2007 pmid=17420245
# Fujimoto2013 pmid=23486481
# Wu2015 pmid=26575439
# Pluvinage2017 pmid=28781080
# Dennis2006 pmid=16565725
# Abbott2009 pmid=19181667
# Hehemann_1_2012 pmid=23150581
# Ficko-Blean2008 pmid=18443291
# Zhu2009 pmid=20081828
# Sogabe2011 pmid=21543843
# Nam2015 pmid=26041776
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# Luis2018 pmid=29255254
# Bule2019 pmid=31645552
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# Yamada2017 pmid=28392148
# Ohnuma2014 pmid=24582745
# Thompson2012 pmid=22219371
# Xie2016 pmid=27777307

# Gregg2015 pmid=26304114

# Williams2014 pmid=24339341
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</biblio>
[[Category:Definitions and explanations]]

Syn/anti lateral protonation

2025-04-02T14:16:55Z

Wim Nerinckx: GH101 is anti

{{CuratorApproved}}
* [[Author]]: [[User:Wim Nerinckx|Wim Nerinckx]]
* [[Responsible Curator]]: [[User:Spencer Williams|Spencer Williams]]

----

== Overview ==

This page provides a table that summarizes the spatial positioning of the catalytic [[general acid]] residue in the active sites of [[glycoside hydrolase]]s, relative to the substrate. The table below updates those found in the seminal paper on this concept by Heightman and Vasella <cite>HeightmanVasella1999</cite>, and a following paper by Nerinckx ''et al.'' <cite>Nerinckx2005</cite>.

== Background ==

The ''"not from above, but from the side"'' concept of semi-lateral glycosidic oxygen [[General_acid/base|protonation]] by [[glycoside hydrolase]]s was introduced by Heightman and Vasella <cite>HeightmanVasella1999</cite>. It was originally only described for [[Anomeric centre (alpha and beta)|beta]]-equatorial [[glycoside hydrolase]]s, but appears to be equally applicable to enzymes acting on an [[Anomeric centre (alpha and beta)|alpha]]-axial glycosidic bond <cite>Nerinckx2005</cite>. When dividing [[Sub-site nomenclature|subsite -1]] into half-spaces by a plane defined by the glycosidic oxygen and C1' and H1' of the –1 glycoside, many ligand-complexed structures reveal that the [[General_acid/base|proton donor]] is positioned either in the ''syn'' half-space (near the ring-oxygen of the –1 glycoside), or in the ''anti'' half-space (on the opposite side of the ring-oxygen). Members of the same GH [[Families|family]] appear to share a common ''syn'' or ''anti'' [[General_acid/base|protonator]] arrangement and further, this specificity appears to be preserved within [[Clans|Clans]] of [[Families|families]]. This page's compilation of [[Sub-site nomenclature|subsite -1]] occupied complexes shows that about 70% of all GH [[Families|families]] are ''anti'' [[General_acid/base|protonators]].

Closer inspection of crystal structures of [[Sub-site nomenclature|–1/+1 subsite]]-spanning substrates, or substrate-analogue ligands, in complex with enzymes reveals a further intriguing corollary <cite>Nerinckx2005 Wu2012</cite>. In substrate-bound complexes with ''anti'' [[General_acid/base|protonating]] GH enzymes, the scissile [[Anomeric centre (alpha and beta)|anomeric bond]] (often studied using the thio-analogue) shows a dihedral angle φ (O5'-C1'-[O,S]x-Cx) that is in the lowest-energy synclinal (gauche) conformation. The rationale for this is that a minus synclinal dihedral angle φ for an equatorial glycosidic bond, or plus synclinal for an axial glycosidic bond <cite>Perez1978</cite>, allows for hyperconjugative overlap of the C1'-O5' antibonding orbital with an antiperiplanar-oriented lone pair orbital lobe of the glycosidic oxygen, thereby creating partial double bond character and stabilization of the glycosidic bond by 4–5 kcal/mol; this ground-state stabilizing phenomenon is known as the ‘exo-anomeric effect’ <cite>Cramer1997 Johnson2009 Alonso2016</cite>. ''Anti'' [[General_acid/base|protonation]] occurs on the glycosidic oxygen’s antiperiplanar lone pair, thereby removing the stabilizing exo-anomeric effect. This suggests that ''anti'' [[General_acid/base|protonation]] is an enzymic approach for lowering the activation barrier leading to the [[Transition state|transition state]] (Figure 1 centre).

''Syn'' [[General_acid/base|protonating]] [[glycoside hydrolase]]s apparently make use of a different approach <cite>Nerinckx2005 Wu2012</cite>. In many [[Sub-site nomenclature|–1/+1 subsite]]-spanning ligand complexes, the dihedral angle φ of the scissile anomeric bond has been rotated away from its lowest-energy synclinal position: clockwise to minus-anticlinal or antiperiplanar for beta-equatorial; counterclockwise to plus-anticlinal or antiperiplanar for alpha-axial [[Anomeric centre (alpha and beta)|anomeric bonds]]. This removes the hyperconjugative overlap and thus also the stabilizing exo-anomeric effect. And because of this rotation, a lone pair of the glycosidic oxygen is directed into the ''syn'' half-space, allowing it to be protonated by the ''syn''-positioned [[General_acid/base|proton donor]] (Figure 1 right).

[[File:Syn_anti.jpg|800px|thumb|center|Figure 1. Newman projections, with the glycosidic oxygen as proximal atom and the anomeric carbon as distal atom, showing ''anti'' (centre) versus ''syn'' (right) semi-lateral [[General_acid/base|protonation]] in beta-equatorial (top) and alpha-axial (bottom) [[glycoside hydrolase]]s. The indicated φ is the dihedral angle for O5'-C1'-O4-C4.]]

== Table of ''syn/anti'' protonation examples ==

This table contains only one example per GH [[Families|family]] of a ligand-complexed protein structure where the ''syn'' or ''anti'' positioning of the [[General_acid/base|proton donor]] can be clearly observed; other examples may be available on a [[Families|family-by-family]] basis. The reader is thus advised to consult the [http://www.cazy.org/fam/acc_GH.html#table CAZy database] for a current, comprehensive list of CAZyme structures. Where available, the selected examples are Michaelis-type complexes with the ligand spanning the [[Sub-site nomenclature|-1/+1 subsites]], since these have an intact glycosidic or thioglycosidic bond, or are ''N''-analogs of the substrate (''e.g.'' acarbose). In some examples, the [[General_acid/base|proton donor]] has been mutated (''e.g.'', to the corresponding amide or to an alanine), and in those cases one may wish to look at a superposition of the given PDB example with the structure of the native enzyme. If a Michaelis-type complex is not yet available, the second and third example choices, respectively, are trapped glycosyl-enzyme [[intermediate]]s and product complexes where [[Sub-site nomenclature|subsite -1]] is occupied.

''Please also be aware that this is a large table with many data. Please contact the page Author or Responsible Curator with corrections.''

=== Table ===
This table can be re-sorted by clicking on the icons in the header (''javascript must be turned on in your browser''). To reset the page to be sorted by GH family, click the ''View'' tab at the very top of the page.

{| {{Prettytable}} class="sortable"
|- valign="top"
! '''Family'''
! '''Clan'''
! '''Structure fold '''
! '''Anomeric specificity'''
! '''Mechanism'''
! '''''Syn/anti'' protonator'''
! '''Example PDB ID'''
! '''Enzyme'''
! '''Organism'''
! '''Ligand'''
! '''General acid'''
! '''Nucleophile or General base'''
! '''Reference'''
|-
| [[GH1]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2cer 2cer]
| β-glycosidase S
| ''Sulfolobus solfataricus'' P2
| phenethyl glucoimidazole
| '''Glu206'''
| Glu387
| <cite>Gloster2006</cite>
|-
| [[GH2]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vzu 2vzu]
| exo-β-glucosaminidase
| ''Amicolatopsis orientalis''
| PNP-β-{{Smallcaps|d}}-glucosamine
| '''Glu469'''
| Glu541
| <cite>van_Bueren2009</cite>
|-
| [[GH3]]
| none
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1iex 1iex]
| exo-1,3-1,4-glucanase
| ''Hordeum vulgare''
| thiocellobiose
| '''Glu491'''
| Asp285
| <cite>Hrmova2001</cite>
|-
| [[GH4]]
| none
| Rossmann + α6/β3 + β3/α4
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1u8x 1u8x]
| 6-P-α-glucosidase
| ''Bacillus subtilis''
| alpha-{{Smallcaps|d}}-glucose-6-phosphate
| '''Asp172'''
| not applicable
| <cite>Rajan2004</cite>
|-
| [[GH5]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1h2j 1h2j]
| endo-β-1,4-glucanase
| ''Bacillus agaradhaerens''
| 2',4'-DNP-2-F-cellobioside
| '''Glu129'''
| Glu228
| <cite>Varrot2003</cite>
|-
| [[GH6]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1qjw 1qjw]
| cellobiohydrolase 2
| ''Hypocrea jecorina''
| (Glc)2-S-(Glc)2
| '''Asp221'''
| debated
| <cite>Zhou1999</cite>
|-
| [[GH7]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1ovw 1ovw]
| endo-1,4-glucanase
| ''Fusarium oxysporum''
| thio-(Glc)5
| '''Glu202'''
| Glu197
| <cite>Sulzenbacher1999</cite>
|-
| [[GH8]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1kwf 1kwf]
| endo-1,4-glucanase
| ''Clostridium thermocellum''
| cellopentaose
| '''Glu95'''
| Asp278
| <cite>Guerin2002</cite>
|-
| [[GH9]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1rq5 1rq5]
| cellobiohydrolase
| ''Clostridium thermocellum''
| cellotetraose
| '''Glu795'''
| Asp383
| <cite>Schubot2004</cite>
|-
| [[GH10]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2d24 2d24]
| β-1,4-xylanase
| ''Streptomyces olivaceoviridis'' E-86
| xylopentaose
| '''Glu128'''
| Glu236
| <cite>Suzuki2009</cite>
|-
| [[GH11]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}4hk8 4hk8]
| endo-β-1,4-xylanase
| ''Hypocrea jecorina''
| xylohexaose
| '''Glu177'''
| Glu86
| <cite>Wan2014</cite>
|-
| [[GH12]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1w2u 1w2u]
| endoglucanase
| ''Humicola grisea''
| thiocellotetraose
| '''Glu205'''
| Glu120
| <cite>Sandgren2004</cite>
|-
| [[GH13]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1cxk 1cxk]
| β-cyclodextrin glucanotransferase
| ''Bacillus circulans''
| maltononaose
| '''Glu257'''
| Asp229
| <cite>Uitdehaag1999</cite>
|-
| [[GH14]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1itc 1itc]
| β-amylase
| ''Bacillus cereus''
| maltopentaose
| '''Glu172'''
| Glu367
| <cite>Miyake2003</cite>
|-
| [[GH15]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1dog 1dog]
| glucoamylase
| ''Aspergillus awamori''
| 1-deoxynojirimycin
| '''Glu179'''
| Glu400
| <cite>Harris1993</cite>
|-
| [[GH16]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1urx 1urx]
| β-agarase A
| ''Zobellia galactanivorans''
| oligoagarose
| '''Glu152'''
| Glu147
| <cite>Allouch2004</cite>
|-
| [[GH17]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzj 4gzj]
| endo-β-1,3-glucanase
| ''Solanum tuberosum''
| laminaratriose + laminarabiose
| '''Glu118'''
| Glu259
| <cite>Wojtkowiak2013</cite>
|-
| [[GH18]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1ffr 1ffr]
| chitinase A
| ''Serratia marcescens''
| (NAG)6
| '''Glu315'''
| internal
| <cite>Papanikolau2001</cite>
|-
| [[GH19]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}3wh1 3wh1]
| chitinase
| ''Bryum coronatum''
| (GlcNAc)4
| '''Glu61'''
| Glu70
| <cite>Ohnuma2014</cite>
|-
| [[GH20]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1c7s 1c7s]
| chitobiase
| ''Serratia marcescens''
| chitobiose
| '''Glu540'''
| internal
| <cite>Prag2000</cite>
|-
| [[GH22]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1h6m 1h6m]
| lysozyme C
| ''Gallus gallus''
| Chit-2-F-chitosyl
| '''Glu35'''
| Asp52
| <cite>Vocadlo2001</cite>
|-
| [[GH23]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1lsp 1lsp]
| lysozyme G
| ''Cygnus atratus''
| Bulgecin A
| '''Glu73'''
| internal
| <cite>Karlsen1996</cite>
|-
| [[GH24]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}148l 148l]
| lysozyme E
| Bacteriophage T4
| chitobiosyl
| '''Glu11'''
| Glu26
| <cite>Baldwin1993</cite>
|-
| [[GH26]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vx6 2vx6]
| exo-β-mannanase
| ''Cellvibrio japonicus'' Ueda107
| Gal1Man4
| '''Glu221'''
| Glu338
| <cite>Cartmell2008</cite>
|-
| [[GH27]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}} / beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3lrm 3lrm]
| α-galactosidase
| ''Saccharomyces cerevisiae''
| raffinose
| '''Asp209'''
| Asp141
| <cite>Fernandez-Leiro2010</cite>
|-
| [[GH28]]
| N
| β-helix
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}2uvf 2uvf]
| exo-polygalacturonosidase
| ''Yersinia enterocolitica'' ATCC9610D
| digalacturonic acid
| '''Asp402'''
| Asp381 Asp403
| <cite>Abbott2007</cite>
|-
| [[GH29]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| '''''syn'''''
| [{{PDBlink}}3uet 3uet]
| α-1,3/4-fucosidase
| ''Bifidobacterium longum'' subsp. infantis
| lacto-''N''-fucopentaose II
| '''Glu217'''
| Asp172
| <cite>Sakurama2012</cite>
|-
| [[GH30]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2y24 2y24]
| glucurono-xylanase
| ''Dickea chrysanthemi'' D1
| glucuronoxylan tetrasaccharide
| '''Glu163'''
| Glu253
| <cite>Urbanikova2011</cite>
|-
| [[GH31]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2qmj 2qmj]
| maltase-glucoamylase
| ''Homo sapiens''
| acarbose
| '''Asp542'''
| Asp443
| <cite>Sim2008</cite>
|-
| [[GH32]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2add 2add]
| fructan β-(2,1)-fructosidase
| ''Cichorium intybus''
| sucrose
| '''Glu201'''
| Asp22
| <cite>Verhaest2007</cite>
|-
| [[GH33]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1s0i 1s0i]
| transsialidase
| ''Trypanosoma cruzi''
| sialyllactose
| '''Asp59'''
| Tyr342
| <cite>Amaya2004</cite>
|-
| [[GH34]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzw 4gzw]
| N2 neuraminidase
| ''Influenza'' A Tanzania/205/2010 H3N2
| α-{{Smallcaps|d}}-Neup5Ac-(2,3)-β-{{Smallcaps|d}}-Galp-(1,4)-β-{{Smallcaps|d}}-GlcpNAc
| '''Asp151'''
| Tyr406
| <cite>Zhu2012</cite>
|-
| [[GH35]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3ogv 3ogv]
| β-galactosidase
| ''Hypocrea jecorina''
| 2-phenylethyl 1-thio-β-{{Smallcaps|d}}-galactopyranoside
| '''Glu200'''
| Glu298
| <cite>Maksimainen2011</cite>
|-
| [[GH36]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4fnu 4fnu]
| β-galactosidase
| ''Geobacillus stearothermophilus''
| stachyose
| '''Asp584'''
| Asp478
| <cite>Merceron2012</cite>
|-
| [[GH37]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2jf4 2jf4]
| trehalase
| ''Escherichia coli''
| validoxylamine
| '''Asp312'''
| Glu496
| <cite>Gibson2007</cite>
|-
| [[GH38]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3czn 3czn]
| Golgi α-mannosidase II
| ''Drosophila melanogaster''
| GlcNAcMan(5)GlcNAc(2)
| '''Asp341'''
| Asp204
| <cite>Shah2008</cite>
|-
| [[GH39]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2bfg 2bfg]
| β-xylosidase
| ''Geobacillus stearothermophilus''
| 2,5-dinitrophenyl-β-{{Smallcaps|d}}-xyloside
| '''Glu160'''
| Glu278
| <cite>Czjzek2005</cite>
|-
| [[GH42]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ucf 4ucf]
| β-galactosidase
| ''Bifidobacterium bifidum''
| {{Smallcaps|d}}-galactose
| '''Glu161'''
| Glu320
| <cite>Godoy2016</cite>
|-
| [[GH43]]
| F
| 5-fold β-propeller
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3akh 3akh]
| exo-1,5-α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces avermitilis''
| α-1,5-arabinofuranotriose
| '''Glu196'''
| Asp220
| <cite>Fujimoto2010</cite>
|-
| [[GH44]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2eqd 2eqd]
| endoglucanase
| ''Clostridium thermocellum''
| cellooctaose
| '''Glu186'''
| Glu359
| <cite>Kitago2007</cite>
|-
| [[GH45]]
| none
| 6-stranded β-barrel
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4eng 4eng]
| endo-1,4-glucanase
| ''Humicola insolens''
| cellohexaose
| '''Asp121'''
| Asp10
| <cite>Davies1996</cite>
|-
| [[GH46]]
| I
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4olt 4olt]
| chitosanase
| ''Microbacterium sp.'' OU01
| hexa-glucosamine
| '''Glu25'''
| Asp43
| <cite>Lyu2014</cite>
|-
| [[GH47]]
| none
| (α/α)7
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1x9d 1x9d]
| α-mannosidase I
| ''Homo sapiens''
| Me-2-S-(α-Man)-2-thio-α-Man
| '''Asp463'''
| Glu599
| <cite>Karaveg2005</cite>, <cite>Nerinckx2008</cite>
|-
| [[GH48]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH8''
|
|
|
|
|
|
|-
| [[GH49]]
| N
| β-helix
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH28''
|
|
|
|
|
|
|-
| [[GH50]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4bq5 4bq5]
| exo-β-agarase
| ''Saccharophagus degradans''
| neoagarotetraose
| '''Glu535'''
| Glu695
| <cite>Pluvinage2013</cite>
|-
| [[GH51]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1qw9 1qw9]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Geobacillus stearothermophilus''
| PNP-{{Smallcaps|l}}-arabinofuranoside
| '''Glu175'''
| Glu294
| <cite>Hoevel2003</cite>
|-
| [[GH52]]
| O
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4c1p 4c1p]
| β-xylosidase
| ''Geobacillus thermoglucosidasius''
| xylobiose
| '''Asp517'''
| Glu537
| <cite>Espina2014</cite>
|-
| [[GH53]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2ccr 2ccr]
| β-1,4-galactanase
| ''Bacillus licheniformis''
| galactotriose
| '''Glu165'''
| Glu263
| <cite>Le_Nours2009</cite>
|-
| [[GH54]]
| none
| β-sandwich
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1wd4 1wd4]
| α-{{Smallcaps|l}}-arabinofuranosidase B
| ''Aspergillus kawachii''
| {{Smallcaps|l}}-arabinofuranose
| '''Asp297'''
| Glu221
| <cite>Miyanaga2004</cite>
|-
| [[GH55]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4tz5 4tz5]
| exo-β-1,3-glucanase
| ''Streptomyces sp.'' SirexAA-E
| laminarihexaose
| '''Glu502'''
| unknown
| <cite>Bianchetti2015</cite>
|-
| [[GH56]]
| none
| (β/α)7
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1fcv 1fcv]
| hyaluronidase
| ''Apis mellifera''
| (hyaluron.)4
| '''Glu113'''
| internal
| <cite>Markovic-Housley2000</cite>
|-
| [[GH57]]
| T
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1k1y 1k1y]
| glucanotransferase
| ''Thermococcus litoralis''
| acarbose
| '''Asp214'''
| Glu123
| <cite>Imamura2003</cite>
|-
| [[GH59]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ccc 4ccc]
| β-galactocerebrosidase
| ''Mus musculus''
| PNP-β-{{Smallcaps|d}}-galactoside
| '''Glu182'''
| Glu258
| <cite>Hill2013</cite>
|-
| [[GH62]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3wn0 3wn0]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces coelicolor''
| β-{{Smallcaps|l}}-Arabinofuranose
| '''Glu361'''
| Asp202
| <cite>Maehara2014</cite>
|-
| [[GH63]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5ca3 5ca3]
| α-glucosidase
| ''Escherichia coli''
| glucose and lactose
| '''Asp501'''
| Glu727
| <cite>Miyazaki2016</cite>
|-
| [[GH65]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}4ktr 4ktr]
| 2-O-α-glucosylglycerol phosphorylase
| ''Bacillus selenitireducens''
| isofagomine
| '''Glu475'''
| phosphate
| <cite>Touhara2014</cite>
|-
| [[GH66]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5axh 5axh]
| dextranase
| ''Thermoanaerobacter pseudethanolicus''
| isomaltohexaose
| '''Glu374'''
| Asp312
| <cite>Suzuki2016</cite>
|-
| [[GH67]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1l8n 1l8n]
| α-glucuronidase
| ''Geobacillus stearothermophilus''
| 4-O-methyl-{{Smallcaps|d}}-glucuronic acid and xylotriose
| '''Glu286'''
| Asp364 Glu392
| <cite>Golan2004</cite>
|-
| [[GH68]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1pt2 1pt2]
| levansucrase
| ''Bacillus subtilis''
| sucrose
| '''Glu342'''
| Asp86
| <cite>Meng2003</cite>
|-
| [[GH70]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3aic 3aic]
| glucansucrase
| ''Streptococcus mutans''
| α-acarbose
| '''Glu515'''
| Asp477
| <cite>Ito2011</cite>
|-
| [[GH72]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w62 2w62]
| β-1,3-glucanotransferase
| ''Saccharomyces cerevisiae'' S288C
| laminaripentaose
| '''Glu176'''
| Glu275
| <cite>Hurtado-Gerrero2009</cite>
|-
| [[GH74]]
| none
| 7-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}2ebs 2ebs]
| cellobiohydrolase (OXG-RCBH)
| ''Geotrichum sp.'' m128
| xyloglucan heptasaccharide
| '''Asp465'''
| Asp35
| <cite>Yaoi2007</cite>
|-
| [[GH76]]
| none
| (α/α)6
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5agd 5agd]
| endo-α-1,6-mannanase
| ''Bacillus circulans''
| α-1,6-mannopentaose
| '''Asp125'''
| Asp124
| <cite>Thompson2015</cite>
|-
| [[GH77]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2oww 2oww]
| 4-α-glucanotransferase
| ''Thermus thermofilus''
| acarbose + 4-deoxy-α-{{Smallcaps|d}}-glucose
| '''Glu340'''
| Asp293
| <cite>Barends2007</cite>
|-
| [[GH78]]
| H
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3w5n 3w5n]
| α-{{Smallcaps|l}}-rhamnosidase
| ''Streptomyces avermitilis''
| {{Smallcaps|l}}-rhamnose
| '''Glu636'''
| Glu895
| <cite>Fujimoto2013</cite>
|-
| [[GH79]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5e9c 5e9c]
| heparanase
| ''Homo sapiens''
| heparin tetrasaccharide
| '''Glu225'''
| Glu343
| <cite>Wu2015</cite>
|-
| [[GH80]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH24''
|
|
|
|
|
|
|-
| [[GH81]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5t4g 5t4g]
| endo-β-1,3-glucanase
| ''Bacillus halodurans'' C-125
| laminarin
| '''Asp466'''
| Glu542
| <cite>Pluvinage2017</cite>
|-
| [[GH83]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1z4x 1z4x]
| hemagglutinin-neuraminidase
| Simian virus 5
| α-2,3-sialyllactose
| '''Glu247''' relay
| Tyr523
| <cite>Yuan2005</cite>
|-
| [[GH84]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2chn 2chn]
| β-''N''-acetyl-glucosaminidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| NAG-thiazoline
| '''Glu242'''
| internal
| <cite>Dennis2006</cite>
|-
| [[GH85]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w92 2w92]
| endo-β-''N''-acetyl-glucosaminidase D
| ''Streptococcus pneumoniae'' TIGR4
| NAG-thiazoline
| '''Glu337'''
| internal
| <cite>Abbott2009</cite>
|-
| [[GH86]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4aw7 4aw7]
| β-porphyranase
| ''Bacteroides plebeius''
| porphyran fragment
| '''Glu152'''
| Glu279
| <cite>Hehemann_1_2012</cite>
|-
| [[GH89]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vcb 2vcb]
| α-''N''-acetyl-glucosaminidase
| ''Clostridium perfringens''
| PUGNAc
| '''Glu483'''
| Glu601
| <cite>Ficko-Blean2008</cite>
|-
| [[GH92]]
| none
| (α/α)6 and β-sandwich
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ww1 2ww1]
| α-1,2-mannosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| thiomannobioside
| '''Glu533'''
| Asp644 Asp642
| <cite>Zhu2009</cite>
|-
| [[GH93]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3a72 3a72]
| exo-arabinanase
| ''Penicillium chrysogenum''
| arabinobiose
| '''Glu246'''
| Glu174
| <cite>Sogabe2011</cite>
|-
| [[GH94]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4zli 4zli]
| cellobionic acid phosphorylase
| ''Saccharophagus degradans''
| 3-O-β-{{Smallcaps|d}}-glucopyranosyl-α-{{Smallcaps|d}}-glucopyranuronic acid
| '''Asp472'''
| phosphate
| <cite>Nam2015</cite>
|-
| [[GH95]]
| none
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ead 2ead]
| α-1,2-{{Smallcaps|l}}-fucosidase
| ''Bifidobacterium bifidum''
| Fuc-α-1,2-Gal
| '''Glu566'''
| Asn423 Asp766
| <cite>Nagae2007</cite>
|-
| [[GH97]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining + inverting
| '''''anti'''''
| [{{PDBlink}}2zq0 2zq0]
| α-glucosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| acarbose
| '''Glu532'''
| Glu508
| <cite>Kitamura2008</cite>
|-
| [[GH98]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2wmg 2wmg]
| endo-β-1,4-galactosidase
| ''Streptococcus pneumoniae''
| A-LewisY pentasaccharide
| '''Glu158'''
| Asp251 Glu301
| <cite>Higgins2009</cite>
|-
| [[GH99]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ad4 4ad4]
| endo-α-mannosidase
| ''Bacteroides xylanisolvens''
| glucose-1,3-isofagomine and α-1,2- mannobiose
| '''Glu336'''
| debated
| <cite>Thompson2012</cite>
|-
| [[GH100]]
| G
| (α/α)6 core
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5gop 5gop]
| invertase
| ''Anabaena (Nostoc) sp.'' pcc7120
| sucrose
| '''Asp188'''
| Glu414
| <cite>Xie2016</cite>

|-
| [[GH101]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5a56 5a56]
| endo-α-N-acetylgalactosaminidase
| ''Streptococcus pneumoniae'' TIGR4
| β-{{Smallcaps|d}}-Galp-(1-3)-α-{{Smallcaps|d}}-GalpNAc-(1)-methyl
| '''Glu796''' +water
| Asp764

| <cite>Gregg2015</cite>

|-

| [[GH102]]
| none
| double-ψ β-barrel
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}2pi8 2pi8]
| lytic transglycosylase A
| ''Escherichia coli''
| chitohexaose
| '''Asp308'''
| none
| <cite>van_Straaten2007</cite>
|-
| [[GH103]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1d0k 1d0k]
| lytic transglycosylase SLT35
| ''Escherichia coli''
| murodipeptides
| '''Glu162'''
| internal
| <cite>van_Asselt2000</cite>
|-
| [[GH106]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5mwk 5mwk]
| α-{{Smallcaps|l}}-rhamnosidase BT_0986
| ''Bacteroides thetaiotaomicron''
| pectin heptasaccharide
| '''Glu461'''
| Glu593 or Glu561
| <cite>Ndeh2017</cite>
|-
| [[GH107]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| ''predicted syn by clan''
| ''see at GH29''
|
|
|
|
|
|
|-
| [[GH110]]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}7jwf 7jwf]
| α-1,3-galactosidase
| ''Pseudoalteromonas distincta''
| Gal-α1,3-Gal
| '''Asp344'''
| Asp321 Asp345
| <cite>McGuire2020</cite>
|-
| [[GH113]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4cd8 4cd8]
| β-mannanase
| ''Alicyclobacillus acidocaldarius''
| mannobioimidazole
| '''Glu151'''
| Glu231
| <cite>Williams2014</cite>
|-
| [[GH116]]
| O
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at GH52''
|
|
|
|
|
|
|-
| [[GH117]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}4ak7 4ak7]
| α-1,3-3,6-anhydro-{{Smallcaps|l}}-galactosidase
| ''Bacteroides plebeius''
| neoagarobiose
| '''His302''' (relay from Asp320)
| Asp90
| <cite>Hehemann_2_2012</cite>
|-
| [[GH119]]
| T
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at GH57''
|
|
|
|
|
|
|-
| [[GH120]]
| none
| parallel β-helix and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3vsv 3vsv]
| β-xylosidase XylC
| ''Thermoanaerobacterium saccharolyticum'' JW/SL-YS485
| {{Smallcaps|d}}-xylose
| '''Glu405'''
| Asp382
| <cite>Huang2012</cite>
|-
| [[GH123]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5fr0 5fr0]
| exo-β-N-acetyl-galactosaminidase
| ''Clostridium perfringens''
| ''N''-difluoroacetyl-{{Smallcaps|d}}-galactosamine
| '''Glu345'''
| internal
| <cite>Noach2016</cite>
|-
| [[GH125]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5m7y 5m7y]
| exo-α-1,6-mannosidase
| ''Clostridium perfringens''
| 1,6-α-mannotriose
| '''Asp220'''
| Glu393
| <cite>Alonso-Gil2016</cite>
|-
| [[GH127]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3wrg 3wrg]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bifidobacterium longum''
| {{Smallcaps|l}}-arabinose
| '''Glu322'''
| Cys417
| <cite>Huang2014</cite>
|-
| [[GH128]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}6ufl 6ufl]
| β-1,3-glucanase
| ''Amycolatopsis mediterranei''
| laminarihexaose
| '''Glu102'''
| Glu199
| <cite>Santos2020</cite>
|-
| [[GH130]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5b0s 5b0s]
| β-1,2-mannobiose phosphorylase
| ''Listeria innocua''
| β-1,2-mannotriose
| '''Asp141''' relay
| phosphate
| <cite>Tsuda2015</cite>
|-
| [[GH134]]
| none
| β + α
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5jug 5jug]
| β-mannanase
| ''Streptomyces sp.''
| mannopentaose
| '''Glu45'''
| Asp57
| <cite>Jin2016</cite>
|-
| [[GH136]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}5gqf 5gqf]
| lacto-N-biosidase
| ''Bifidobacterium longum''
| lacto-N-biose
| '''Asp411'''
| Asp418
| <cite>Yamada2017</cite>
|-
| [[GH137]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|l}}
| unknown
| '''''anti'''''
| [{{PDBlink}}5mui 5mui]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0996
| ''Bacteroides thetaiotaomicron''
| pectin oligosaccharide
| '''Glu240'''
| Glu159
| <cite>Ndeh2017</cite>
|-
| [[GH138]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}6hzg 6hzg]
| α-1,2-{{Smallcaps|d}}-galacturonidase
| ''Bacteroides paurosaccharolyticus''
| alpha-{{Smallcaps|d}}-galactopyranuronic
| '''Glu294'''
| Glu361
| <cite>Labourel2019</cite>
|-
| [[GH140]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH146]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5opj 5opj]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0349
| ''Bacteroides thetaiotaomicron''
| {{Smallcaps|l}}-arabinose
| '''Glu320'''
| Cys416
| <cite>Luis2018</cite>
|-
| [[GH147]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH148]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH149]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH156]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}6s0e 6s0e]
| exo-α-sialidase
| uncultured bacterium pG7
| N-acetyl-2,3-dehydro-2-deoxyneuraminic acid
| '''His134''' (relay from Asp132)
| Asp14
| <cite>Bule2019</cite>
|-
| [[GH157]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH158]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH161]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH162]]
| S
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}6imw 6imw]
| endo-β-1,2-glucanase
| ''Talaromyces funiculosus''
| beta-1,2-glucan
| '''Glu262''' via C3-OH of glc at subs. +2
| Asp446
| <cite>Tanaka2019</cite>
|-
| [[GH164]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}6t75 6t75]
| β-mannosidase
| ''Bacteroides salyersiae''
| 2-deoxy-2-F-mannosyl
| '''Glu160'''
| Glu297
| <cite>Armstrong2020</cite>
|-
| [[GH167]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|-
| [[GH169]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH172]]
| none
| β-jelly roll
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}7v1w 7v1w]
| difructose-anhydride synthase
| ''Bifidobacterium dentum''
| beta-{{Smallcaps|d}}-arabinofuranose
| '''Glu270'''
| Glu291
| <cite>Kashima2021</cite>
|-
| [[GH173]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH178]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at e.g. GH15''
|
|
|
|

|
|-
| [[GH181]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}8axi 8axi]
| exo-α-sialidase
| ''Akkermansia muciniphila''
| 2-deoxy-2,3-dehydro-''N''-acetyl-neuraminic acid + T-antigen disaccharide
| '''Asp345'''
| Glu218
| <cite>Shuoker2023</cite>
|-
| [[GH183]]
| none
| 5-bladed β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}8ic1 8ic1]
| endo-α-1,5-{{Smallcaps|d}}-arabinofuranosidase
| ''Microbacterium arabinogalactanolyticum'' JCM 9171
| α-{{Smallcaps|d}}-Araf-(1,5)-α-{{Smallcaps|d}}-Araf-(1,5)-α-{{Smallcaps|d}}-Araf-(1,5)-α-{{Smallcaps|d}}-Araf
| '''Asp51'''
| Asp33
| <cite>Shimokawa2023</cite>
|-
| [[GH186]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}8ip1 8ip1]
| β-1,2-glucanase
| ''Escherechia coli''
| β-1,2-glucan
| '''Asp388'''
| Asp300 + 3 waters
| <cite>Motouchi2023</cite>
|-
| [http://www.cazy.org/GH0.html n.c.*]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2vjj 2vjj]
| endo-α-N-acetylglucosaminidase
| Bacteriophage HK620
| O18A1 O-antigen hexasaccharide
| '''Asp339'''
| Glu372
| <cite>Barbirz2008</cite>
|}
<nowiki>*</nowiki> n.c.: Found among the collection of [http://www.cazy.org/GH0.html non-classified GH sequences in the CAZy Database].

== References ==

<biblio>
# HeightmanVasella1999 Heightman TD and Vasella AT. ''Recent Insights into Inhibition, Structure, and Mechanism of Configuration-Retaining Glycosidases.'' Angew Chem Int Ed. 1999 38(6):750-770. [http://www3.interscience.wiley.com/journal/55000581/abstract Article online].
# Nerinckx2005 pmid=15642336
# Wu2012 pmid=23137336
# Perez1978 Pérez S and Marchessault RH. ''The exo-anomeric effect: experimental evidence from crystal structures.'' Carbohydr res. 1978 65:114-120. [http://dx.doi.org/10.1016/S0008-6215(00)84218-4 DOI:10.1016/S0008-6215(00)84218-4]
# Cramer1997 Cramer CJ, Truhlar DG, and French AD. ''Exo-anomeric effects on energies and geometries of different conformations of glucose and related systems in the gas phase and aqueous solution.'' Carbohydr res. 1997 298:1-14. [http://dx.doi.org/10.1016/S0008-6215(96)00297-2 DOI:10.1016/S0008-6215(96)00297-2]
# Johnson2009 pmid=19733839
# Alonso2016 pmid=26889578
# Gloster2006 pmid=17002288
# van_Bueren2009 pmid=18976664
# Hrmova2001 pmid=11709165
# Rajan2004 pmid=15341727
# Varrot2003 pmid=12595701
# Zhou1999 pmid=10508787
# Sulzenbacher1999 pmid=10200171
# Urbanikova2011 pmid=21501386
# Guerin2002 pmid=11884144
# Schubot2004 pmid=14756552
# Suzuki2009 pmid=19279191
# Wan2014 pmid=24419374
# Sandgren2004 pmid=15364577
# Uitdehaag1999 pmid=10331869
# Miyake2003 pmid=12741813
# Harris1993 pmid=8431441
# Allouch2004 pmid=15062085
# Wojtkowiak2013 pmid=23275163
# Papanikolau2001 pmid=11560481
# Prag2000 pmid=10884356
# Vocadlo2001 pmid=11518970
# Karlsen1996 pmid=15299731
# Baldwin1993 pmid=8259514
# Cartmell2008 pmid=18799462
# Fernandez-Leiro2010 pmid=20592022
# Abbott2007 pmid=17397864
# Sakurama2012 pmid=22451675
# Sim2008 pmid=18036614
# Verhaest2007 pmid=17335500
# Amaya2004 pmid=15130470
# Zhu2012 pmid=23015718
# Maksimainen2011 pmid=21130883
# Merceron2012 pmid=23012371
# Gibson2007 pmid=17455176
# Shah2008 pmid=18599462
# Czjzek2005 pmid=16212978
# Godoy2016 pmid=27685756
# Fujimoto2010 pmid=20739278
# Kitago2007 pmid=17905739
# Davies1996 pmid=15299721
# Lyu2014 pmid=24766439
# Karaveg2005 pmid=15713668
# Nerinckx2008 pmid=18619586
# Pluvinage2013 pmid=23921382
# Yuan2005 pmid=15893670
# Hoevel2003 pmid=14517232
# Espina2014 pmid=24816105
# Le_Nours2009 pmid=19089956
# Miyanaga2004 pmid=15292273
# Bianchetti2015 pmid=25752603
# Markovic-Housley2000 pmid=11080624
# Imamura2003 pmid=12618437
# Hill2013 pmid=24297913
# Maehara2014 pmid=24482228
# Miyazaki2016 pmid=27688023
# Touhara2014 pmid=24828502
# Suzuki2016 pmid=26494689
# Golan2004 pmid=14573597
# Meng2003 pmid=14517548
# Ito2011 pmid=21354427
# Hurtado-Gerrero2009 pmid=19097997
# Yaoi2007 pmid=17498741
# Thompson2015 pmid=25772148
# Barends2007 pmid=17420245
# Fujimoto2013 pmid=23486481
# Wu2015 pmid=26575439
# Pluvinage2017 pmid=28781080
# Dennis2006 pmid=16565725
# Abbott2009 pmid=19181667
# Hehemann_1_2012 pmid=23150581
# Ficko-Blean2008 pmid=18443291
# Zhu2009 pmid=20081828
# Sogabe2011 pmid=21543843
# Nam2015 pmid=26041776
# Nagae2007 pmid=17459873
# Kitamura2008 pmid=18981178
# Higgins2009 pmid=19608744
# van_Straaten2007 pmid=17502382
# van_Asselt2000 pmid=10684641
# Ndeh2017 pmid=28329766
# Labourel2019 pmid=30877196
# Luis2018 pmid=29255254
# Bule2019 pmid=31645552
# Jin2016 Jin Y, Petricevic M, John A, Raich L, Jenkins H, Portela De Souza L, Cuskin F, Gilbert HJ, Rovira C, Goddard-Borger ED, Williams SJ, and Davies GJ. ''A β-Mannanase with a Lysozyme-like Fold and a Novel Molecular Catalytic Mechanism.'' ACS Cent Sci. 2016 Nov [http://dx.doi.org/10.1021/acscentsci.6b00232 DOI:10.1021/acscentsci.6b00232]
# Yamada2017 pmid=28392148
# Ohnuma2014 pmid=24582745
# Thompson2012 pmid=22219371
# Xie2016 pmid=27777307

# Gregg2015 pmid=26304114

# Williams2014 pmid=24339341
# Hehemann_2_2012 pmid=22393053
# Huang2012 pmid=22992047
# Noach2016 pmid=27038508
# Alonso-Gil2016 pmid=28026180
# Huang2014 Huang CH, Zhu Z, Cheng YS, Chan HC, Ko TP, Chen CC, Wang I, Ho MR, Hsu ST, Zeng YF, Huang YN, Liu JR, Guo RT. ''Structure and Catalytic Mechanism of a Glycoside Hydrolase Family-127 β-L-Arabinofuranosidase (HypBA1).'' J Bioprocess Biotech. 2014 4:171 [http://dx.doi.org/10.4172/2155-9821.1000171 DOI:10.4172/2155-9821.1000171]
# Tsuda2015 pmid=26632508
# Barbirz2008 pmid=18547389
# Tanaka2019 pmid=30926603
# Armstrong2020 pmid=31871050
# Santos2020 pmid=32451508
# Kashima2021 pmid=34688653
# McGuire2020 pmid=33127644
# Shuoker2023 pmid=37005422
# Shimokawa2023 pmid=37726269
# Motouchi2023 pmid=37735577

</biblio>
[[Category:Definitions and explanations]]

Syn/anti lateral protonation

2025-04-02T13:50:51Z

Wim Nerinckx: clan-member update

{{CuratorApproved}}
* [[Author]]: [[User:Wim Nerinckx|Wim Nerinckx]]
* [[Responsible Curator]]: [[User:Spencer Williams|Spencer Williams]]

----

== Overview ==

This page provides a table that summarizes the spatial positioning of the catalytic [[general acid]] residue in the active sites of [[glycoside hydrolase]]s, relative to the substrate. The table below updates those found in the seminal paper on this concept by Heightman and Vasella <cite>HeightmanVasella1999</cite>, and a following paper by Nerinckx ''et al.'' <cite>Nerinckx2005</cite>.

== Background ==

The ''"not from above, but from the side"'' concept of semi-lateral glycosidic oxygen [[General_acid/base|protonation]] by [[glycoside hydrolase]]s was introduced by Heightman and Vasella <cite>HeightmanVasella1999</cite>. It was originally only described for [[Anomeric centre (alpha and beta)|beta]]-equatorial [[glycoside hydrolase]]s, but appears to be equally applicable to enzymes acting on an [[Anomeric centre (alpha and beta)|alpha]]-axial glycosidic bond <cite>Nerinckx2005</cite>. When dividing [[Sub-site nomenclature|subsite -1]] into half-spaces by a plane defined by the glycosidic oxygen and C1' and H1' of the –1 glycoside, many ligand-complexed structures reveal that the [[General_acid/base|proton donor]] is positioned either in the ''syn'' half-space (near the ring-oxygen of the –1 glycoside), or in the ''anti'' half-space (on the opposite side of the ring-oxygen). Members of the same GH [[Families|family]] appear to share a common ''syn'' or ''anti'' [[General_acid/base|protonator]] arrangement and further, this specificity appears to be preserved within [[Clans|Clans]] of [[Families|families]]. This page's compilation of [[Sub-site nomenclature|subsite -1]] occupied complexes shows that about 70% of all GH [[Families|families]] are ''anti'' [[General_acid/base|protonators]].

Closer inspection of crystal structures of [[Sub-site nomenclature|–1/+1 subsite]]-spanning substrates, or substrate-analogue ligands, in complex with enzymes reveals a further intriguing corollary <cite>Nerinckx2005 Wu2012</cite>. In substrate-bound complexes with ''anti'' [[General_acid/base|protonating]] GH enzymes, the scissile [[Anomeric centre (alpha and beta)|anomeric bond]] (often studied using the thio-analogue) shows a dihedral angle φ (O5'-C1'-[O,S]x-Cx) that is in the lowest-energy synclinal (gauche) conformation. The rationale for this is that a minus synclinal dihedral angle φ for an equatorial glycosidic bond, or plus synclinal for an axial glycosidic bond <cite>Perez1978</cite>, allows for hyperconjugative overlap of the C1'-O5' antibonding orbital with an antiperiplanar-oriented lone pair orbital lobe of the glycosidic oxygen, thereby creating partial double bond character and stabilization of the glycosidic bond by 4–5 kcal/mol; this ground-state stabilizing phenomenon is known as the ‘exo-anomeric effect’ <cite>Cramer1997 Johnson2009 Alonso2016</cite>. ''Anti'' [[General_acid/base|protonation]] occurs on the glycosidic oxygen’s antiperiplanar lone pair, thereby removing the stabilizing exo-anomeric effect. This suggests that ''anti'' [[General_acid/base|protonation]] is an enzymic approach for lowering the activation barrier leading to the [[Transition state|transition state]] (Figure 1 centre).

''Syn'' [[General_acid/base|protonating]] [[glycoside hydrolase]]s apparently make use of a different approach <cite>Nerinckx2005 Wu2012</cite>. In many [[Sub-site nomenclature|–1/+1 subsite]]-spanning ligand complexes, the dihedral angle φ of the scissile anomeric bond has been rotated away from its lowest-energy synclinal position: clockwise to minus-anticlinal or antiperiplanar for beta-equatorial; counterclockwise to plus-anticlinal or antiperiplanar for alpha-axial [[Anomeric centre (alpha and beta)|anomeric bonds]]. This removes the hyperconjugative overlap and thus also the stabilizing exo-anomeric effect. And because of this rotation, a lone pair of the glycosidic oxygen is directed into the ''syn'' half-space, allowing it to be protonated by the ''syn''-positioned [[General_acid/base|proton donor]] (Figure 1 right).

[[File:Syn_anti.jpg|800px|thumb|center|Figure 1. Newman projections, with the glycosidic oxygen as proximal atom and the anomeric carbon as distal atom, showing ''anti'' (centre) versus ''syn'' (right) semi-lateral [[General_acid/base|protonation]] in beta-equatorial (top) and alpha-axial (bottom) [[glycoside hydrolase]]s. The indicated φ is the dihedral angle for O5'-C1'-O4-C4.]]

== Table of ''syn/anti'' protonation examples ==

This table contains only one example per GH [[Families|family]] of a ligand-complexed protein structure where the ''syn'' or ''anti'' positioning of the [[General_acid/base|proton donor]] can be clearly observed; other examples may be available on a [[Families|family-by-family]] basis. The reader is thus advised to consult the [http://www.cazy.org/fam/acc_GH.html#table CAZy database] for a current, comprehensive list of CAZyme structures. Where available, the selected examples are Michaelis-type complexes with the ligand spanning the [[Sub-site nomenclature|-1/+1 subsites]], since these have an intact glycosidic or thioglycosidic bond, or are ''N''-analogs of the substrate (''e.g.'' acarbose). In some examples, the [[General_acid/base|proton donor]] has been mutated (''e.g.'', to the corresponding amide or to an alanine), and in those cases one may wish to look at a superposition of the given PDB example with the structure of the native enzyme. If a Michaelis-type complex is not yet available, the second and third example choices, respectively, are trapped glycosyl-enzyme [[intermediate]]s and product complexes where [[Sub-site nomenclature|subsite -1]] is occupied.

''Please also be aware that this is a large table with many data. Please contact the page Author or Responsible Curator with corrections.''

=== Table ===
This table can be re-sorted by clicking on the icons in the header (''javascript must be turned on in your browser''). To reset the page to be sorted by GH family, click the ''View'' tab at the very top of the page.

{| {{Prettytable}} class="sortable"
|- valign="top"
! '''Family'''
! '''Clan'''
! '''Structure fold '''
! '''Anomeric specificity'''
! '''Mechanism'''
! '''''Syn/anti'' protonator'''
! '''Example PDB ID'''
! '''Enzyme'''
! '''Organism'''
! '''Ligand'''
! '''General acid'''
! '''Nucleophile or General base'''
! '''Reference'''
|-
| [[GH1]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2cer 2cer]
| β-glycosidase S
| ''Sulfolobus solfataricus'' P2
| phenethyl glucoimidazole
| '''Glu206'''
| Glu387
| <cite>Gloster2006</cite>
|-
| [[GH2]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vzu 2vzu]
| exo-β-glucosaminidase
| ''Amicolatopsis orientalis''
| PNP-β-{{Smallcaps|d}}-glucosamine
| '''Glu469'''
| Glu541
| <cite>van_Bueren2009</cite>
|-
| [[GH3]]
| none
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1iex 1iex]
| exo-1,3-1,4-glucanase
| ''Hordeum vulgare''
| thiocellobiose
| '''Glu491'''
| Asp285
| <cite>Hrmova2001</cite>
|-
| [[GH4]]
| none
| Rossmann + α6/β3 + β3/α4
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1u8x 1u8x]
| 6-P-α-glucosidase
| ''Bacillus subtilis''
| alpha-{{Smallcaps|d}}-glucose-6-phosphate
| '''Asp172'''
| not applicable
| <cite>Rajan2004</cite>
|-
| [[GH5]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1h2j 1h2j]
| endo-β-1,4-glucanase
| ''Bacillus agaradhaerens''
| 2',4'-DNP-2-F-cellobioside
| '''Glu129'''
| Glu228
| <cite>Varrot2003</cite>
|-
| [[GH6]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1qjw 1qjw]
| cellobiohydrolase 2
| ''Hypocrea jecorina''
| (Glc)2-S-(Glc)2
| '''Asp221'''
| debated
| <cite>Zhou1999</cite>
|-
| [[GH7]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1ovw 1ovw]
| endo-1,4-glucanase
| ''Fusarium oxysporum''
| thio-(Glc)5
| '''Glu202'''
| Glu197
| <cite>Sulzenbacher1999</cite>
|-
| [[GH8]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1kwf 1kwf]
| endo-1,4-glucanase
| ''Clostridium thermocellum''
| cellopentaose
| '''Glu95'''
| Asp278
| <cite>Guerin2002</cite>
|-
| [[GH9]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1rq5 1rq5]
| cellobiohydrolase
| ''Clostridium thermocellum''
| cellotetraose
| '''Glu795'''
| Asp383
| <cite>Schubot2004</cite>
|-
| [[GH10]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2d24 2d24]
| β-1,4-xylanase
| ''Streptomyces olivaceoviridis'' E-86
| xylopentaose
| '''Glu128'''
| Glu236
| <cite>Suzuki2009</cite>
|-
| [[GH11]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}4hk8 4hk8]
| endo-β-1,4-xylanase
| ''Hypocrea jecorina''
| xylohexaose
| '''Glu177'''
| Glu86
| <cite>Wan2014</cite>
|-
| [[GH12]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1w2u 1w2u]
| endoglucanase
| ''Humicola grisea''
| thiocellotetraose
| '''Glu205'''
| Glu120
| <cite>Sandgren2004</cite>
|-
| [[GH13]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1cxk 1cxk]
| β-cyclodextrin glucanotransferase
| ''Bacillus circulans''
| maltononaose
| '''Glu257'''
| Asp229
| <cite>Uitdehaag1999</cite>
|-
| [[GH14]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1itc 1itc]
| β-amylase
| ''Bacillus cereus''
| maltopentaose
| '''Glu172'''
| Glu367
| <cite>Miyake2003</cite>
|-
| [[GH15]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1dog 1dog]
| glucoamylase
| ''Aspergillus awamori''
| 1-deoxynojirimycin
| '''Glu179'''
| Glu400
| <cite>Harris1993</cite>
|-
| [[GH16]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1urx 1urx]
| β-agarase A
| ''Zobellia galactanivorans''
| oligoagarose
| '''Glu152'''
| Glu147
| <cite>Allouch2004</cite>
|-
| [[GH17]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzj 4gzj]
| endo-β-1,3-glucanase
| ''Solanum tuberosum''
| laminaratriose + laminarabiose
| '''Glu118'''
| Glu259
| <cite>Wojtkowiak2013</cite>
|-
| [[GH18]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1ffr 1ffr]
| chitinase A
| ''Serratia marcescens''
| (NAG)6
| '''Glu315'''
| internal
| <cite>Papanikolau2001</cite>
|-
| [[GH19]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}3wh1 3wh1]
| chitinase
| ''Bryum coronatum''
| (GlcNAc)4
| '''Glu61'''
| Glu70
| <cite>Ohnuma2014</cite>
|-
| [[GH20]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1c7s 1c7s]
| chitobiase
| ''Serratia marcescens''
| chitobiose
| '''Glu540'''
| internal
| <cite>Prag2000</cite>
|-
| [[GH22]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1h6m 1h6m]
| lysozyme C
| ''Gallus gallus''
| Chit-2-F-chitosyl
| '''Glu35'''
| Asp52
| <cite>Vocadlo2001</cite>
|-
| [[GH23]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1lsp 1lsp]
| lysozyme G
| ''Cygnus atratus''
| Bulgecin A
| '''Glu73'''
| internal
| <cite>Karlsen1996</cite>
|-
| [[GH24]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}148l 148l]
| lysozyme E
| Bacteriophage T4
| chitobiosyl
| '''Glu11'''
| Glu26
| <cite>Baldwin1993</cite>
|-
| [[GH26]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vx6 2vx6]
| exo-β-mannanase
| ''Cellvibrio japonicus'' Ueda107
| Gal1Man4
| '''Glu221'''
| Glu338
| <cite>Cartmell2008</cite>
|-
| [[GH27]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}} / beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3lrm 3lrm]
| α-galactosidase
| ''Saccharomyces cerevisiae''
| raffinose
| '''Asp209'''
| Asp141
| <cite>Fernandez-Leiro2010</cite>
|-
| [[GH28]]
| N
| β-helix
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}2uvf 2uvf]
| exo-polygalacturonosidase
| ''Yersinia enterocolitica'' ATCC9610D
| digalacturonic acid
| '''Asp402'''
| Asp381 Asp403
| <cite>Abbott2007</cite>
|-
| [[GH29]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| '''''syn'''''
| [{{PDBlink}}3uet 3uet]
| α-1,3/4-fucosidase
| ''Bifidobacterium longum'' subsp. infantis
| lacto-''N''-fucopentaose II
| '''Glu217'''
| Asp172
| <cite>Sakurama2012</cite>
|-
| [[GH30]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2y24 2y24]
| glucurono-xylanase
| ''Dickea chrysanthemi'' D1
| glucuronoxylan tetrasaccharide
| '''Glu163'''
| Glu253
| <cite>Urbanikova2011</cite>
|-
| [[GH31]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2qmj 2qmj]
| maltase-glucoamylase
| ''Homo sapiens''
| acarbose
| '''Asp542'''
| Asp443
| <cite>Sim2008</cite>
|-
| [[GH32]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2add 2add]
| fructan β-(2,1)-fructosidase
| ''Cichorium intybus''
| sucrose
| '''Glu201'''
| Asp22
| <cite>Verhaest2007</cite>
|-
| [[GH33]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1s0i 1s0i]
| transsialidase
| ''Trypanosoma cruzi''
| sialyllactose
| '''Asp59'''
| Tyr342
| <cite>Amaya2004</cite>
|-
| [[GH34]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzw 4gzw]
| N2 neuraminidase
| ''Influenza'' A Tanzania/205/2010 H3N2
| α-{{Smallcaps|d}}-Neup5Ac-(2,3)-β-{{Smallcaps|d}}-Galp-(1,4)-β-{{Smallcaps|d}}-GlcpNAc
| '''Asp151'''
| Tyr406
| <cite>Zhu2012</cite>
|-
| [[GH35]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3ogv 3ogv]
| β-galactosidase
| ''Hypocrea jecorina''
| 2-phenylethyl 1-thio-β-{{Smallcaps|d}}-galactopyranoside
| '''Glu200'''
| Glu298
| <cite>Maksimainen2011</cite>
|-
| [[GH36]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4fnu 4fnu]
| β-galactosidase
| ''Geobacillus stearothermophilus''
| stachyose
| '''Asp584'''
| Asp478
| <cite>Merceron2012</cite>
|-
| [[GH37]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2jf4 2jf4]
| trehalase
| ''Escherichia coli''
| validoxylamine
| '''Asp312'''
| Glu496
| <cite>Gibson2007</cite>
|-
| [[GH38]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3czn 3czn]
| Golgi α-mannosidase II
| ''Drosophila melanogaster''
| GlcNAcMan(5)GlcNAc(2)
| '''Asp341'''
| Asp204
| <cite>Shah2008</cite>
|-
| [[GH39]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2bfg 2bfg]
| β-xylosidase
| ''Geobacillus stearothermophilus''
| 2,5-dinitrophenyl-β-{{Smallcaps|d}}-xyloside
| '''Glu160'''
| Glu278
| <cite>Czjzek2005</cite>
|-
| [[GH42]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ucf 4ucf]
| β-galactosidase
| ''Bifidobacterium bifidum''
| {{Smallcaps|d}}-galactose
| '''Glu161'''
| Glu320
| <cite>Godoy2016</cite>
|-
| [[GH43]]
| F
| 5-fold β-propeller
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3akh 3akh]
| exo-1,5-α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces avermitilis''
| α-1,5-arabinofuranotriose
| '''Glu196'''
| Asp220
| <cite>Fujimoto2010</cite>
|-
| [[GH44]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2eqd 2eqd]
| endoglucanase
| ''Clostridium thermocellum''
| cellooctaose
| '''Glu186'''
| Glu359
| <cite>Kitago2007</cite>
|-
| [[GH45]]
| none
| 6-stranded β-barrel
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4eng 4eng]
| endo-1,4-glucanase
| ''Humicola insolens''
| cellohexaose
| '''Asp121'''
| Asp10
| <cite>Davies1996</cite>
|-
| [[GH46]]
| I
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4olt 4olt]
| chitosanase
| ''Microbacterium sp.'' OU01
| hexa-glucosamine
| '''Glu25'''
| Asp43
| <cite>Lyu2014</cite>
|-
| [[GH47]]
| none
| (α/α)7
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1x9d 1x9d]
| α-mannosidase I
| ''Homo sapiens''
| Me-2-S-(α-Man)-2-thio-α-Man
| '''Asp463'''
| Glu599
| <cite>Karaveg2005</cite>, <cite>Nerinckx2008</cite>
|-
| [[GH48]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH8''
|
|
|
|
|
|
|-
| [[GH49]]
| N
| β-helix
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH28''
|
|
|
|
|
|
|-
| [[GH50]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4bq5 4bq5]
| exo-β-agarase
| ''Saccharophagus degradans''
| neoagarotetraose
| '''Glu535'''
| Glu695
| <cite>Pluvinage2013</cite>
|-
| [[GH51]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1qw9 1qw9]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Geobacillus stearothermophilus''
| PNP-{{Smallcaps|l}}-arabinofuranoside
| '''Glu175'''
| Glu294
| <cite>Hoevel2003</cite>
|-
| [[GH52]]
| O
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4c1p 4c1p]
| β-xylosidase
| ''Geobacillus thermoglucosidasius''
| xylobiose
| '''Asp517'''
| Glu537
| <cite>Espina2014</cite>
|-
| [[GH53]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2ccr 2ccr]
| β-1,4-galactanase
| ''Bacillus licheniformis''
| galactotriose
| '''Glu165'''
| Glu263
| <cite>Le_Nours2009</cite>
|-
| [[GH54]]
| none
| β-sandwich
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1wd4 1wd4]
| α-{{Smallcaps|l}}-arabinofuranosidase B
| ''Aspergillus kawachii''
| {{Smallcaps|l}}-arabinofuranose
| '''Asp297'''
| Glu221
| <cite>Miyanaga2004</cite>
|-
| [[GH55]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4tz5 4tz5]
| exo-β-1,3-glucanase
| ''Streptomyces sp.'' SirexAA-E
| laminarihexaose
| '''Glu502'''
| unknown
| <cite>Bianchetti2015</cite>
|-
| [[GH56]]
| none
| (β/α)7
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1fcv 1fcv]
| hyaluronidase
| ''Apis mellifera''
| (hyaluron.)4
| '''Glu113'''
| internal
| <cite>Markovic-Housley2000</cite>
|-
| [[GH57]]
| T
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1k1y 1k1y]
| glucanotransferase
| ''Thermococcus litoralis''
| acarbose
| '''Asp214'''
| Glu123
| <cite>Imamura2003</cite>
|-
| [[GH59]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ccc 4ccc]
| β-galactocerebrosidase
| ''Mus musculus''
| PNP-β-{{Smallcaps|d}}-galactoside
| '''Glu182'''
| Glu258
| <cite>Hill2013</cite>
|-
| [[GH62]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3wn0 3wn0]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces coelicolor''
| β-{{Smallcaps|l}}-Arabinofuranose
| '''Glu361'''
| Asp202
| <cite>Maehara2014</cite>
|-
| [[GH63]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5ca3 5ca3]
| α-glucosidase
| ''Escherichia coli''
| glucose and lactose
| '''Asp501'''
| Glu727
| <cite>Miyazaki2016</cite>
|-
| [[GH65]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}4ktr 4ktr]
| 2-O-α-glucosylglycerol phosphorylase
| ''Bacillus selenitireducens''
| isofagomine
| '''Glu475'''
| phosphate
| <cite>Touhara2014</cite>
|-
| [[GH66]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5axh 5axh]
| dextranase
| ''Thermoanaerobacter pseudethanolicus''
| isomaltohexaose
| '''Glu374'''
| Asp312
| <cite>Suzuki2016</cite>
|-
| [[GH67]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1l8n 1l8n]
| α-glucuronidase
| ''Geobacillus stearothermophilus''
| 4-O-methyl-{{Smallcaps|d}}-glucuronic acid and xylotriose
| '''Glu286'''
| Asp364 Glu392
| <cite>Golan2004</cite>
|-
| [[GH68]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1pt2 1pt2]
| levansucrase
| ''Bacillus subtilis''
| sucrose
| '''Glu342'''
| Asp86
| <cite>Meng2003</cite>
|-
| [[GH70]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3aic 3aic]
| glucansucrase
| ''Streptococcus mutans''
| α-acarbose
| '''Glu515'''
| Asp477
| <cite>Ito2011</cite>
|-
| [[GH72]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w62 2w62]
| β-1,3-glucanotransferase
| ''Saccharomyces cerevisiae'' S288C
| laminaripentaose
| '''Glu176'''
| Glu275
| <cite>Hurtado-Gerrero2009</cite>
|-
| [[GH74]]
| none
| 7-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}2ebs 2ebs]
| cellobiohydrolase (OXG-RCBH)
| ''Geotrichum sp.'' m128
| xyloglucan heptasaccharide
| '''Asp465'''
| Asp35
| <cite>Yaoi2007</cite>
|-
| [[GH76]]
| none
| (α/α)6
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5agd 5agd]
| endo-α-1,6-mannanase
| ''Bacillus circulans''
| α-1,6-mannopentaose
| '''Asp125'''
| Asp124
| <cite>Thompson2015</cite>
|-
| [[GH77]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2oww 2oww]
| 4-α-glucanotransferase
| ''Thermus thermofilus''
| acarbose + 4-deoxy-α-{{Smallcaps|d}}-glucose
| '''Glu340'''
| Asp293
| <cite>Barends2007</cite>
|-
| [[GH78]]
| H
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3w5n 3w5n]
| α-{{Smallcaps|l}}-rhamnosidase
| ''Streptomyces avermitilis''
| {{Smallcaps|l}}-rhamnose
| '''Glu636'''
| Glu895
| <cite>Fujimoto2013</cite>
|-
| [[GH79]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5e9c 5e9c]
| heparanase
| ''Homo sapiens''
| heparin tetrasaccharide
| '''Glu225'''
| Glu343
| <cite>Wu2015</cite>
|-
| [[GH80]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH24''
|
|
|
|
|
|
|-
| [[GH81]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5t4g 5t4g]
| endo-β-1,3-glucanase
| ''Bacillus halodurans'' C-125
| laminarin
| '''Asp466'''
| Glu542
| <cite>Pluvinage2017</cite>
|-
| [[GH83]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1z4x 1z4x]
| hemagglutinin-neuraminidase
| Simian virus 5
| α-2,3-sialyllactose
| '''Glu247''' relay
| Tyr523
| <cite>Yuan2005</cite>
|-
| [[GH84]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2chn 2chn]
| β-''N''-acetyl-glucosaminidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| NAG-thiazoline
| '''Glu242'''
| internal
| <cite>Dennis2006</cite>
|-
| [[GH85]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w92 2w92]
| endo-β-''N''-acetyl-glucosaminidase D
| ''Streptococcus pneumoniae'' TIGR4
| NAG-thiazoline
| '''Glu337'''
| internal
| <cite>Abbott2009</cite>
|-
| [[GH86]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4aw7 4aw7]
| β-porphyranase
| ''Bacteroides plebeius''
| porphyran fragment
| '''Glu152'''
| Glu279
| <cite>Hehemann_1_2012</cite>
|-
| [[GH89]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vcb 2vcb]
| α-''N''-acetyl-glucosaminidase
| ''Clostridium perfringens''
| PUGNAc
| '''Glu483'''
| Glu601
| <cite>Ficko-Blean2008</cite>
|-
| [[GH92]]
| none
| (α/α)6 and β-sandwich
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ww1 2ww1]
| α-1,2-mannosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| thiomannobioside
| '''Glu533'''
| Asp644 Asp642
| <cite>Zhu2009</cite>
|-
| [[GH93]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3a72 3a72]
| exo-arabinanase
| ''Penicillium chrysogenum''
| arabinobiose
| '''Glu246'''
| Glu174
| <cite>Sogabe2011</cite>
|-
| [[GH94]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4zli 4zli]
| cellobionic acid phosphorylase
| ''Saccharophagus degradans''
| 3-O-β-{{Smallcaps|d}}-glucopyranosyl-α-{{Smallcaps|d}}-glucopyranuronic acid
| '''Asp472'''
| phosphate
| <cite>Nam2015</cite>
|-
| [[GH95]]
| none
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ead 2ead]
| α-1,2-{{Smallcaps|l}}-fucosidase
| ''Bifidobacterium bifidum''
| Fuc-α-1,2-Gal
| '''Glu566'''
| Asn423 Asp766
| <cite>Nagae2007</cite>
|-
| [[GH97]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining + inverting
| '''''anti'''''
| [{{PDBlink}}2zq0 2zq0]
| α-glucosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| acarbose
| '''Glu532'''
| Glu508
| <cite>Kitamura2008</cite>
|-
| [[GH98]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2wmg 2wmg]
| endo-β-1,4-galactosidase
| ''Streptococcus pneumoniae''
| A-LewisY pentasaccharide
| '''Glu158'''
| Asp251 Glu301
| <cite>Higgins2009</cite>
|-
| [[GH99]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ad4 4ad4]
| endo-α-mannosidase
| ''Bacteroides xylanisolvens''
| glucose-1,3-isofagomine and α-1,2- mannobiose
| '''Glu336'''
| debated
| <cite>Thompson2012</cite>
|-
| [[GH100]]
| G
| (α/α)6 core
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5gop 5gop]
| invertase
| ''Anabaena (Nostoc) sp.'' pcc7120
| sucrose
| '''Asp188'''
| Glu414
| <cite>Xie2016</cite>
|-
| [[GH102]]
| none
| double-ψ β-barrel
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}2pi8 2pi8]
| lytic transglycosylase A
| ''Escherichia coli''
| chitohexaose
| '''Asp308'''
| none
| <cite>van_Straaten2007</cite>
|-
| [[GH103]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1d0k 1d0k]
| lytic transglycosylase SLT35
| ''Escherichia coli''
| murodipeptides
| '''Glu162'''
| internal
| <cite>van_Asselt2000</cite>
|-
| [[GH106]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5mwk 5mwk]
| α-{{Smallcaps|l}}-rhamnosidase BT_0986
| ''Bacteroides thetaiotaomicron''
| pectin heptasaccharide
| '''Glu461'''
| Glu593 or Glu561
| <cite>Ndeh2017</cite>
|-
| [[GH107]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| ''predicted syn by clan''
| ''see at GH29''
|
|
|
|
|
|
|-
| [[GH110]]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}7jwf 7jwf]
| α-1,3-galactosidase
| ''Pseudoalteromonas distincta''
| Gal-α1,3-Gal
| '''Asp344'''
| Asp321 Asp345
| <cite>McGuire2020</cite>
|-
| [[GH113]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4cd8 4cd8]
| β-mannanase
| ''Alicyclobacillus acidocaldarius''
| mannobioimidazole
| '''Glu151'''
| Glu231
| <cite>Williams2014</cite>
|-
| [[GH116]]
| O
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at GH52''
|
|
|
|
|
|
|-
| [[GH117]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}4ak7 4ak7]
| α-1,3-3,6-anhydro-{{Smallcaps|l}}-galactosidase
| ''Bacteroides plebeius''
| neoagarobiose
| '''His302''' (relay from Asp320)
| Asp90
| <cite>Hehemann_2_2012</cite>
|-
| [[GH119]]
| T
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at GH57''
|
|
|
|
|
|
|-
| [[GH120]]
| none
| parallel β-helix and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3vsv 3vsv]
| β-xylosidase XylC
| ''Thermoanaerobacterium saccharolyticum'' JW/SL-YS485
| {{Smallcaps|d}}-xylose
| '''Glu405'''
| Asp382
| <cite>Huang2012</cite>
|-
| [[GH123]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5fr0 5fr0]
| exo-β-N-acetyl-galactosaminidase
| ''Clostridium perfringens''
| ''N''-difluoroacetyl-{{Smallcaps|d}}-galactosamine
| '''Glu345'''
| internal
| <cite>Noach2016</cite>
|-
| [[GH125]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5m7y 5m7y]
| exo-α-1,6-mannosidase
| ''Clostridium perfringens''
| 1,6-α-mannotriose
| '''Asp220'''
| Glu393
| <cite>Alonso-Gil2016</cite>
|-
| [[GH127]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3wrg 3wrg]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bifidobacterium longum''
| {{Smallcaps|l}}-arabinose
| '''Glu322'''
| Cys417
| <cite>Huang2014</cite>
|-
| [[GH128]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}6ufl 6ufl]
| β-1,3-glucanase
| ''Amycolatopsis mediterranei''
| laminarihexaose
| '''Glu102'''
| Glu199
| <cite>Santos2020</cite>
|-
| [[GH130]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5b0s 5b0s]
| β-1,2-mannobiose phosphorylase
| ''Listeria innocua''
| β-1,2-mannotriose
| '''Asp141''' relay
| phosphate
| <cite>Tsuda2015</cite>
|-
| [[GH134]]
| none
| β + α
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5jug 5jug]
| β-mannanase
| ''Streptomyces sp.''
| mannopentaose
| '''Glu45'''
| Asp57
| <cite>Jin2016</cite>
|-
| [[GH136]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}5gqf 5gqf]
| lacto-N-biosidase
| ''Bifidobacterium longum''
| lacto-N-biose
| '''Asp411'''
| Asp418
| <cite>Yamada2017</cite>
|-
| [[GH137]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|l}}
| unknown
| '''''anti'''''
| [{{PDBlink}}5mui 5mui]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0996
| ''Bacteroides thetaiotaomicron''
| pectin oligosaccharide
| '''Glu240'''
| Glu159
| <cite>Ndeh2017</cite>
|-
| [[GH138]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}6hzg 6hzg]
| α-1,2-{{Smallcaps|d}}-galacturonidase
| ''Bacteroides paurosaccharolyticus''
| alpha-{{Smallcaps|d}}-galactopyranuronic
| '''Glu294'''
| Glu361
| <cite>Labourel2019</cite>
|-
| [[GH140]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH146]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5opj 5opj]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0349
| ''Bacteroides thetaiotaomicron''
| {{Smallcaps|l}}-arabinose
| '''Glu320'''
| Cys416
| <cite>Luis2018</cite>
|-
| [[GH147]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH148]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH149]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH156]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}6s0e 6s0e]
| exo-α-sialidase
| uncultured bacterium pG7
| N-acetyl-2,3-dehydro-2-deoxyneuraminic acid
| '''His134''' (relay from Asp132)
| Asp14
| <cite>Bule2019</cite>
|-
| [[GH157]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH158]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH161]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH162]]
| S
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}6imw 6imw]
| endo-β-1,2-glucanase
| ''Talaromyces funiculosus''
| beta-1,2-glucan
| '''Glu262''' via C3-OH of glc at subs. +2
| Asp446
| <cite>Tanaka2019</cite>
|-
| [[GH164]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}6t75 6t75]
| β-mannosidase
| ''Bacteroides salyersiae''
| 2-deoxy-2-F-mannosyl
| '''Glu160'''
| Glu297
| <cite>Armstrong2020</cite>
|-
| [[GH167]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|-
| [[GH169]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH172]]
| none
| β-jelly roll
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}7v1w 7v1w]
| difructose-anhydride synthase
| ''Bifidobacterium dentum''
| beta-{{Smallcaps|d}}-arabinofuranose
| '''Glu270'''
| Glu291
| <cite>Kashima2021</cite>
|-
| [[GH173]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH178]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at e.g. GH15''
|
|
|
|

|
|-
| [[GH181]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}8axi 8axi]
| exo-α-sialidase
| ''Akkermansia muciniphila''
| 2-deoxy-2,3-dehydro-''N''-acetyl-neuraminic acid + T-antigen disaccharide
| '''Asp345'''
| Glu218
| <cite>Shuoker2023</cite>
|-
| [[GH183]]
| none
| 5-bladed β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}8ic1 8ic1]
| endo-α-1,5-{{Smallcaps|d}}-arabinofuranosidase
| ''Microbacterium arabinogalactanolyticum'' JCM 9171
| α-{{Smallcaps|d}}-Araf-(1,5)-α-{{Smallcaps|d}}-Araf-(1,5)-α-{{Smallcaps|d}}-Araf-(1,5)-α-{{Smallcaps|d}}-Araf
| '''Asp51'''
| Asp33
| <cite>Shimokawa2023</cite>
|-
| [[GH186]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}8ip1 8ip1]
| β-1,2-glucanase
| ''Escherechia coli''
| β-1,2-glucan
| '''Asp388'''
| Asp300 + 3 waters
| <cite>Motouchi2023</cite>
|-
| [http://www.cazy.org/GH0.html n.c.*]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2vjj 2vjj]
| endo-α-N-acetylglucosaminidase
| Bacteriophage HK620
| O18A1 O-antigen hexasaccharide
| '''Asp339'''
| Glu372
| <cite>Barbirz2008</cite>
|}
<nowiki>*</nowiki> n.c.: Found among the collection of [http://www.cazy.org/GH0.html non-classified GH sequences in the CAZy Database].

== References ==

<biblio>
# HeightmanVasella1999 Heightman TD and Vasella AT. ''Recent Insights into Inhibition, Structure, and Mechanism of Configuration-Retaining Glycosidases.'' Angew Chem Int Ed. 1999 38(6):750-770. [http://www3.interscience.wiley.com/journal/55000581/abstract Article online].
# Nerinckx2005 pmid=15642336
# Wu2012 pmid=23137336
# Perez1978 Pérez S and Marchessault RH. ''The exo-anomeric effect: experimental evidence from crystal structures.'' Carbohydr res. 1978 65:114-120. [http://dx.doi.org/10.1016/S0008-6215(00)84218-4 DOI:10.1016/S0008-6215(00)84218-4]
# Cramer1997 Cramer CJ, Truhlar DG, and French AD. ''Exo-anomeric effects on energies and geometries of different conformations of glucose and related systems in the gas phase and aqueous solution.'' Carbohydr res. 1997 298:1-14. [http://dx.doi.org/10.1016/S0008-6215(96)00297-2 DOI:10.1016/S0008-6215(96)00297-2]
# Johnson2009 pmid=19733839
# Alonso2016 pmid=26889578
# Gloster2006 pmid=17002288
# van_Bueren2009 pmid=18976664
# Hrmova2001 pmid=11709165
# Rajan2004 pmid=15341727
# Varrot2003 pmid=12595701
# Zhou1999 pmid=10508787
# Sulzenbacher1999 pmid=10200171
# Urbanikova2011 pmid=21501386
# Guerin2002 pmid=11884144
# Schubot2004 pmid=14756552
# Suzuki2009 pmid=19279191
# Wan2014 pmid=24419374
# Sandgren2004 pmid=15364577
# Uitdehaag1999 pmid=10331869
# Miyake2003 pmid=12741813
# Harris1993 pmid=8431441
# Allouch2004 pmid=15062085
# Wojtkowiak2013 pmid=23275163
# Papanikolau2001 pmid=11560481
# Prag2000 pmid=10884356
# Vocadlo2001 pmid=11518970
# Karlsen1996 pmid=15299731
# Baldwin1993 pmid=8259514
# Cartmell2008 pmid=18799462
# Fernandez-Leiro2010 pmid=20592022
# Abbott2007 pmid=17397864
# Sakurama2012 pmid=22451675
# Sim2008 pmid=18036614
# Verhaest2007 pmid=17335500
# Amaya2004 pmid=15130470
# Zhu2012 pmid=23015718
# Maksimainen2011 pmid=21130883
# Merceron2012 pmid=23012371
# Gibson2007 pmid=17455176
# Shah2008 pmid=18599462
# Czjzek2005 pmid=16212978
# Godoy2016 pmid=27685756
# Fujimoto2010 pmid=20739278
# Kitago2007 pmid=17905739
# Davies1996 pmid=15299721
# Lyu2014 pmid=24766439
# Karaveg2005 pmid=15713668
# Nerinckx2008 pmid=18619586
# Pluvinage2013 pmid=23921382
# Yuan2005 pmid=15893670
# Hoevel2003 pmid=14517232
# Espina2014 pmid=24816105
# Le_Nours2009 pmid=19089956
# Miyanaga2004 pmid=15292273
# Bianchetti2015 pmid=25752603
# Markovic-Housley2000 pmid=11080624
# Imamura2003 pmid=12618437
# Hill2013 pmid=24297913
# Maehara2014 pmid=24482228
# Miyazaki2016 pmid=27688023
# Touhara2014 pmid=24828502
# Suzuki2016 pmid=26494689
# Golan2004 pmid=14573597
# Meng2003 pmid=14517548
# Ito2011 pmid=21354427
# Hurtado-Gerrero2009 pmid=19097997
# Yaoi2007 pmid=17498741
# Thompson2015 pmid=25772148
# Barends2007 pmid=17420245
# Fujimoto2013 pmid=23486481
# Wu2015 pmid=26575439
# Pluvinage2017 pmid=28781080
# Dennis2006 pmid=16565725
# Abbott2009 pmid=19181667
# Hehemann_1_2012 pmid=23150581
# Ficko-Blean2008 pmid=18443291
# Zhu2009 pmid=20081828
# Sogabe2011 pmid=21543843
# Nam2015 pmid=26041776
# Nagae2007 pmid=17459873
# Kitamura2008 pmid=18981178
# Higgins2009 pmid=19608744
# van_Straaten2007 pmid=17502382
# van_Asselt2000 pmid=10684641
# Ndeh2017 pmid=28329766
# Labourel2019 pmid=30877196
# Luis2018 pmid=29255254
# Bule2019 pmid=31645552
# Jin2016 Jin Y, Petricevic M, John A, Raich L, Jenkins H, Portela De Souza L, Cuskin F, Gilbert HJ, Rovira C, Goddard-Borger ED, Williams SJ, and Davies GJ. ''A β-Mannanase with a Lysozyme-like Fold and a Novel Molecular Catalytic Mechanism.'' ACS Cent Sci. 2016 Nov [http://dx.doi.org/10.1021/acscentsci.6b00232 DOI:10.1021/acscentsci.6b00232]
# Yamada2017 pmid=28392148
# Ohnuma2014 pmid=24582745
# Thompson2012 pmid=22219371
# Xie2016 pmid=27777307
# Williams2014 pmid=24339341
# Hehemann_2_2012 pmid=22393053
# Huang2012 pmid=22992047
# Noach2016 pmid=27038508
# Alonso-Gil2016 pmid=28026180
# Huang2014 Huang CH, Zhu Z, Cheng YS, Chan HC, Ko TP, Chen CC, Wang I, Ho MR, Hsu ST, Zeng YF, Huang YN, Liu JR, Guo RT. ''Structure and Catalytic Mechanism of a Glycoside Hydrolase Family-127 β-L-Arabinofuranosidase (HypBA1).'' J Bioprocess Biotech. 2014 4:171 [http://dx.doi.org/10.4172/2155-9821.1000171 DOI:10.4172/2155-9821.1000171]
# Tsuda2015 pmid=26632508
# Barbirz2008 pmid=18547389
# Tanaka2019 pmid=30926603
# Armstrong2020 pmid=31871050
# Santos2020 pmid=32451508
# Kashima2021 pmid=34688653
# McGuire2020 pmid=33127644
# Shuoker2023 pmid=37005422
# Shimokawa2023 pmid=37726269
# Motouchi2023 pmid=37735577

</biblio>
[[Category:Definitions and explanations]]

Syn/anti lateral protonation

2024-10-29T09:46:19Z

Wim Nerinckx: Added GH186 syn protonator

{{CuratorApproved}}
* [[Author]]: [[User:Wim Nerinckx|Wim Nerinckx]]
* [[Responsible Curator]]: [[User:Spencer Williams|Spencer Williams]]

----

== Overview ==

This page provides a table that summarizes the spatial positioning of the catalytic [[general acid]] residue in the active sites of [[glycoside hydrolase]]s, relative to the substrate. The table below updates those found in the seminal paper on this concept by Heightman and Vasella <cite>HeightmanVasella1999</cite>, and a following paper by Nerinckx ''et al.'' <cite>Nerinckx2005</cite>.

== Background ==

The ''"not from above, but from the side"'' concept of semi-lateral glycosidic oxygen [[General_acid/base|protonation]] by [[glycoside hydrolase]]s was introduced by Heightman and Vasella <cite>HeightmanVasella1999</cite>. It was originally only described for [[Anomeric centre (alpha and beta)|beta]]-equatorial [[glycoside hydrolase]]s, but appears to be equally applicable to enzymes acting on an [[Anomeric centre (alpha and beta)|alpha]]-axial glycosidic bond <cite>Nerinckx2005</cite>. When dividing [[Sub-site nomenclature|subsite -1]] into half-spaces by a plane defined by the glycosidic oxygen and C1' and H1' of the –1 glycoside, many ligand-complexed structures reveal that the [[General_acid/base|proton donor]] is positioned either in the ''syn'' half-space (near the ring-oxygen of the –1 glycoside), or in the ''anti'' half-space (on the opposite side of the ring-oxygen). Members of the same GH [[Families|family]] appear to share a common ''syn'' or ''anti'' [[General_acid/base|protonator]] arrangement and further, this specificity appears to be preserved within [[Clans|Clans]] of [[Families|families]]. This page's compilation of [[Sub-site nomenclature|subsite -1]] occupied complexes shows that about 70% of all GH [[Families|families]] are ''anti'' [[General_acid/base|protonators]].

Closer inspection of crystal structures of [[Sub-site nomenclature|–1/+1 subsite]]-spanning substrates, or substrate-analogue ligands, in complex with enzymes reveals a further intriguing corollary <cite>Nerinckx2005 Wu2012</cite>. In substrate-bound complexes with ''anti'' [[General_acid/base|protonating]] GH enzymes, the scissile [[Anomeric centre (alpha and beta)|anomeric bond]] (often studied using the thio-analogue) shows a dihedral angle φ (O5'-C1'-[O,S]x-Cx) that is in the lowest-energy synclinal (gauche) conformation. The rationale for this is that a minus synclinal dihedral angle φ for an equatorial glycosidic bond, or plus synclinal for an axial glycosidic bond <cite>Perez1978</cite>, allows for hyperconjugative overlap of the C1'-O5' antibonding orbital with an antiperiplanar-oriented lone pair orbital lobe of the glycosidic oxygen, thereby creating partial double bond character and stabilization of the glycosidic bond by 4–5 kcal/mol; this ground-state stabilizing phenomenon is known as the ‘exo-anomeric effect’ <cite>Cramer1997 Johnson2009 Alonso2016</cite>. ''Anti'' [[General_acid/base|protonation]] occurs on the glycosidic oxygen’s antiperiplanar lone pair, thereby removing the stabilizing exo-anomeric effect. This suggests that ''anti'' [[General_acid/base|protonation]] is an enzymic approach for lowering the activation barrier leading to the [[Transition state|transition state]] (Figure 1 centre).

''Syn'' [[General_acid/base|protonating]] [[glycoside hydrolase]]s apparently make use of a different approach <cite>Nerinckx2005 Wu2012</cite>. In many [[Sub-site nomenclature|–1/+1 subsite]]-spanning ligand complexes, the dihedral angle φ of the scissile anomeric bond has been rotated away from its lowest-energy synclinal position: clockwise to minus-anticlinal or antiperiplanar for beta-equatorial; counterclockwise to plus-anticlinal or antiperiplanar for alpha-axial [[Anomeric centre (alpha and beta)|anomeric bonds]]. This removes the hyperconjugative overlap and thus also the stabilizing exo-anomeric effect. And because of this rotation, a lone pair of the glycosidic oxygen is directed into the ''syn'' half-space, allowing it to be protonated by the ''syn''-positioned [[General_acid/base|proton donor]] (Figure 1 right).

[[File:Syn_anti.jpg|800px|thumb|center|Figure 1. Newman projections, with the glycosidic oxygen as proximal atom and the anomeric carbon as distal atom, showing ''anti'' (centre) versus ''syn'' (right) semi-lateral [[General_acid/base|protonation]] in beta-equatorial (top) and alpha-axial (bottom) [[glycoside hydrolase]]s. The indicated φ is the dihedral angle for O5'-C1'-O4-C4.]]

== Table of ''syn/anti'' protonation examples ==

This table contains only one example per GH [[Families|family]] of a ligand-complexed protein structure where the ''syn'' or ''anti'' positioning of the [[General_acid/base|proton donor]] can be clearly observed; other examples may be available on a [[Families|family-by-family]] basis. The reader is thus advised to consult the [http://www.cazy.org/fam/acc_GH.html#table CAZy database] for a current, comprehensive list of CAZyme structures. Where available, the selected examples are Michaelis-type complexes with the ligand spanning the [[Sub-site nomenclature|-1/+1 subsites]], since these have an intact glycosidic or thioglycosidic bond, or are ''N''-analogs of the substrate (''e.g.'' acarbose). In some examples, the [[General_acid/base|proton donor]] has been mutated (''e.g.'', to the corresponding amide or to an alanine), and in those cases one may wish to look at a superposition of the given PDB example with the structure of the native enzyme. If a Michaelis-type complex is not yet available, the second and third example choices, respectively, are trapped glycosyl-enzyme [[intermediate]]s and product complexes where [[Sub-site nomenclature|subsite -1]] is occupied.

''Please also be aware that this is a large table with many data. Please contact the page Author or Responsible Curator with corrections.''

=== Table ===
This table can be re-sorted by clicking on the icons in the header (''javascript must be turned on in your browser''). To reset the page to be sorted by GH family, click the ''View'' tab at the very top of the page.

{| {{Prettytable}} class="sortable"
|- valign="top"
! '''Family'''
! '''Clan'''
! '''Structure fold '''
! '''Anomeric specificity'''
! '''Mechanism'''
! '''''Syn/anti'' protonator'''
! '''Example PDB ID'''
! '''Enzyme'''
! '''Organism'''
! '''Ligand'''
! '''General acid'''
! '''Nucleophile or General base'''
! '''Reference'''
|-
| [[GH1]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2cer 2cer]
| β-glycosidase S
| ''Sulfolobus solfataricus'' P2
| phenethyl glucoimidazole
| '''Glu206'''
| Glu387
| <cite>Gloster2006</cite>
|-
| [[GH2]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vzu 2vzu]
| exo-β-glucosaminidase
| ''Amicolatopsis orientalis''
| PNP-β-{{Smallcaps|d}}-glucosamine
| '''Glu469'''
| Glu541
| <cite>van_Bueren2009</cite>
|-
| [[GH3]]
| none
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1iex 1iex]
| exo-1,3-1,4-glucanase
| ''Hordeum vulgare''
| thiocellobiose
| '''Glu491'''
| Asp285
| <cite>Hrmova2001</cite>
|-
| [[GH4]]
| none
| Rossmann + α6/β3 + β3/α4
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1u8x 1u8x]
| 6-P-α-glucosidase
| ''Bacillus subtilis''
| alpha-{{Smallcaps|d}}-glucose-6-phosphate
| '''Asp172'''
| not applicable
| <cite>Rajan2004</cite>
|-
| [[GH5]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1h2j 1h2j]
| endo-β-1,4-glucanase
| ''Bacillus agaradhaerens''
| 2',4'-DNP-2-F-cellobioside
| '''Glu129'''
| Glu228
| <cite>Varrot2003</cite>
|-
| [[GH6]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1qjw 1qjw]
| cellobiohydrolase 2
| ''Hypocrea jecorina''
| (Glc)2-S-(Glc)2
| '''Asp221'''
| debated
| <cite>Zhou1999</cite>
|-
| [[GH7]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1ovw 1ovw]
| endo-1,4-glucanase
| ''Fusarium oxysporum''
| thio-(Glc)5
| '''Glu202'''
| Glu197
| <cite>Sulzenbacher1999</cite>
|-
| [[GH8]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1kwf 1kwf]
| endo-1,4-glucanase
| ''Clostridium thermocellum''
| cellopentaose
| '''Glu95'''
| Asp278
| <cite>Guerin2002</cite>
|-
| [[GH9]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1rq5 1rq5]
| cellobiohydrolase
| ''Clostridium thermocellum''
| cellotetraose
| '''Glu795'''
| Asp383
| <cite>Schubot2004</cite>
|-
| [[GH10]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2d24 2d24]
| β-1,4-xylanase
| ''Streptomyces olivaceoviridis'' E-86
| xylopentaose
| '''Glu128'''
| Glu236
| <cite>Suzuki2009</cite>
|-
| [[GH11]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}4hk8 4hk8]
| endo-β-1,4-xylanase
| ''Hypocrea jecorina''
| xylohexaose
| '''Glu177'''
| Glu86
| <cite>Wan2014</cite>
|-
| [[GH12]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1w2u 1w2u]
| endoglucanase
| ''Humicola grisea''
| thiocellotetraose
| '''Glu205'''
| Glu120
| <cite>Sandgren2004</cite>
|-
| [[GH13]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1cxk 1cxk]
| β-cyclodextrin glucanotransferase
| ''Bacillus circulans''
| maltononaose
| '''Glu257'''
| Asp229
| <cite>Uitdehaag1999</cite>
|-
| [[GH14]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1itc 1itc]
| β-amylase
| ''Bacillus cereus''
| maltopentaose
| '''Glu172'''
| Glu367
| <cite>Miyake2003</cite>
|-
| [[GH15]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1dog 1dog]
| glucoamylase
| ''Aspergillus awamori''
| 1-deoxynojirimycin
| '''Glu179'''
| Glu400
| <cite>Harris1993</cite>
|-
| [[GH16]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1urx 1urx]
| β-agarase A
| ''Zobellia galactanivorans''
| oligoagarose
| '''Glu152'''
| Glu147
| <cite>Allouch2004</cite>
|-
| [[GH17]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzj 4gzj]
| endo-β-1,3-glucanase
| ''Solanum tuberosum''
| laminaratriose + laminarabiose
| '''Glu118'''
| Glu259
| <cite>Wojtkowiak2013</cite>
|-
| [[GH18]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1ffr 1ffr]
| chitinase A
| ''Serratia marcescens''
| (NAG)6
| '''Glu315'''
| internal
| <cite>Papanikolau2001</cite>
|-
| [[GH19]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}3wh1 3wh1]
| chitinase
| ''Bryum coronatum''
| (GlcNAc)4
| '''Glu61'''
| Glu70
| <cite>Ohnuma2014</cite>
|-
| [[GH20]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1c7s 1c7s]
| chitobiase
| ''Serratia marcescens''
| chitobiose
| '''Glu540'''
| internal
| <cite>Prag2000</cite>
|-
| [[GH22]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1h6m 1h6m]
| lysozyme C
| ''Gallus gallus''
| Chit-2-F-chitosyl
| '''Glu35'''
| Asp52
| <cite>Vocadlo2001</cite>
|-
| [[GH23]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1lsp 1lsp]
| lysozyme G
| ''Cygnus atratus''
| Bulgecin A
| '''Glu73'''
| internal
| <cite>Karlsen1996</cite>
|-
| [[GH24]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}148l 148l]
| lysozyme E
| Bacteriophage T4
| chitobiosyl
| '''Glu11'''
| Glu26
| <cite>Baldwin1993</cite>
|-
| [[GH26]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vx6 2vx6]
| exo-β-mannanase
| ''Cellvibrio japonicus'' Ueda107
| Gal1Man4
| '''Glu221'''
| Glu338
| <cite>Cartmell2008</cite>
|-
| [[GH27]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}} / beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3lrm 3lrm]
| α-galactosidase
| ''Saccharomyces cerevisiae''
| raffinose
| '''Asp209'''
| Asp141
| <cite>Fernandez-Leiro2010</cite>
|-
| [[GH28]]
| N
| β-helix
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}2uvf 2uvf]
| exo-polygalacturonosidase
| ''Yersinia enterocolitica'' ATCC9610D
| digalacturonic acid
| '''Asp402'''
| Asp381 Asp403
| <cite>Abbott2007</cite>
|-
| [[GH29]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| '''''syn'''''
| [{{PDBlink}}3uet 3uet]
| α-1,3/4-fucosidase
| ''Bifidobacterium longum'' subsp. infantis
| lacto-''N''-fucopentaose II
| '''Glu217'''
| Asp172
| <cite>Sakurama2012</cite>
|-
| [[GH30]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2y24 2y24]
| glucurono-xylanase
| ''Dickea chrysanthemi'' D1
| glucuronoxylan tetrasaccharide
| '''Glu163'''
| Glu253
| <cite>Urbanikova2011</cite>
|-
| [[GH31]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2qmj 2qmj]
| maltase-glucoamylase
| ''Homo sapiens''
| acarbose
| '''Asp542'''
| Asp443
| <cite>Sim2008</cite>
|-
| [[GH32]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2add 2add]
| fructan β-(2,1)-fructosidase
| ''Cichorium intybus''
| sucrose
| '''Glu201'''
| Asp22
| <cite>Verhaest2007</cite>
|-
| [[GH33]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1s0i 1s0i]
| transsialidase
| ''Trypanosoma cruzi''
| sialyllactose
| '''Asp59'''
| Tyr342
| <cite>Amaya2004</cite>
|-
| [[GH34]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzw 4gzw]
| N2 neuraminidase
| ''Influenza'' A Tanzania/205/2010 H3N2
| α-{{Smallcaps|d}}-Neup5Ac-(2,3)-β-{{Smallcaps|d}}-Galp-(1,4)-β-{{Smallcaps|d}}-GlcpNAc
| '''Asp151'''
| Tyr406
| <cite>Zhu2012</cite>
|-
| [[GH35]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3ogv 3ogv]
| β-galactosidase
| ''Hypocrea jecorina''
| 2-phenylethyl 1-thio-β-{{Smallcaps|d}}-galactopyranoside
| '''Glu200'''
| Glu298
| <cite>Maksimainen2011</cite>
|-
| [[GH36]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4fnu 4fnu]
| β-galactosidase
| ''Geobacillus stearothermophilus''
| stachyose
| '''Asp584'''
| Asp478
| <cite>Merceron2012</cite>
|-
| [[GH37]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2jf4 2jf4]
| trehalase
| ''Escherichia coli''
| validoxylamine
| '''Asp312'''
| Glu496
| <cite>Gibson2007</cite>
|-
| [[GH38]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3czn 3czn]
| Golgi α-mannosidase II
| ''Drosophila melanogaster''
| GlcNAcMan(5)GlcNAc(2)
| '''Asp341'''
| Asp204
| <cite>Shah2008</cite>
|-
| [[GH39]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2bfg 2bfg]
| β-xylosidase
| ''Geobacillus stearothermophilus''
| 2,5-dinitrophenyl-β-{{Smallcaps|d}}-xyloside
| '''Glu160'''
| Glu278
| <cite>Czjzek2005</cite>
|-
| [[GH42]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ucf 4ucf]
| β-galactosidase
| ''Bifidobacterium bifidum''
| {{Smallcaps|d}}-galactose
| '''Glu161'''
| Glu320
| <cite>Godoy2016</cite>
|-
| [[GH43]]
| F
| 5-fold β-propeller
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3akh 3akh]
| exo-1,5-α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces avermitilis''
| α-1,5-arabinofuranotriose
| '''Glu196'''
| Asp220
| <cite>Fujimoto2010</cite>
|-
| [[GH44]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2eqd 2eqd]
| endoglucanase
| ''Clostridium thermocellum''
| cellooctaose
| '''Glu186'''
| Glu359
| <cite>Kitago2007</cite>
|-
| [[GH45]]
| none
| 6-stranded β-barrel
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4eng 4eng]
| endo-1,4-glucanase
| ''Humicola insolens''
| cellohexaose
| '''Asp121'''
| Asp10
| <cite>Davies1996</cite>
|-
| [[GH46]]
| I
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4olt 4olt]
| chitosanase
| ''Microbacterium sp.'' OU01
| hexa-glucosamine
| '''Glu25'''
| Asp43
| <cite>Lyu2014</cite>
|-
| [[GH47]]
| none
| (α/α)7
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1x9d 1x9d]
| α-mannosidase I
| ''Homo sapiens''
| Me-2-S-(α-Man)-2-thio-α-Man
| '''Asp463'''
| Glu599
| <cite>Karaveg2005</cite>, <cite>Nerinckx2008</cite>
|-
| [[GH48]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH8''
|
|
|
|
|
|
|-
| [[GH49]]
| N
| β-helix
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH28''
|
|
|
|
|
|
|-
| [[GH50]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4bq5 4bq5]
| exo-β-agarase
| ''Saccharophagus degradans''
| neoagarotetraose
| '''Glu535'''
| Glu695
| <cite>Pluvinage2013</cite>
|-
| [[GH51]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1qw9 1qw9]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Geobacillus stearothermophilus''
| PNP-{{Smallcaps|l}}-arabinofuranoside
| '''Glu175'''
| Glu294
| <cite>Hoevel2003</cite>
|-
| [[GH52]]
| O
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4c1p 4c1p]
| β-xylosidase
| ''Geobacillus thermoglucosidasius''
| xylobiose
| '''Asp517'''
| Glu537
| <cite>Espina2014</cite>
|-
| [[GH53]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2ccr 2ccr]
| β-1,4-galactanase
| ''Bacillus licheniformis''
| galactotriose
| '''Glu165'''
| Glu263
| <cite>Le_Nours2009</cite>
|-
| [[GH54]]
| none
| β-sandwich
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1wd4 1wd4]
| α-{{Smallcaps|l}}-arabinofuranosidase B
| ''Aspergillus kawachii''
| {{Smallcaps|l}}-arabinofuranose
| '''Asp297'''
| Glu221
| <cite>Miyanaga2004</cite>
|-
| [[GH55]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4tz5 4tz5]
| exo-β-1,3-glucanase
| ''Streptomyces sp.'' SirexAA-E
| laminarihexaose
| '''Glu502'''
| unknown
| <cite>Bianchetti2015</cite>
|-
| [[GH56]]
| none
| (β/α)7
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1fcv 1fcv]
| hyaluronidase
| ''Apis mellifera''
| (hyaluron.)4
| '''Glu113'''
| internal
| <cite>Markovic-Housley2000</cite>
|-
| [[GH57]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1k1y 1k1y]
| glucanotransferase
| ''Thermococcus litoralis''
| acarbose
| '''Asp214'''
| Glu123
| <cite>Imamura2003</cite>
|-
| [[GH59]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ccc 4ccc]
| β-galactocerebrosidase
| ''Mus musculus''
| PNP-β-{{Smallcaps|d}}-galactoside
| '''Glu182'''
| Glu258
| <cite>Hill2013</cite>
|-
| [[GH62]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3wn0 3wn0]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces coelicolor''
| β-{{Smallcaps|l}}-Arabinofuranose
| '''Glu361'''
| Asp202
| <cite>Maehara2014</cite>
|-
| [[GH63]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5ca3 5ca3]
| α-glucosidase
| ''Escherichia coli''
| glucose and lactose
| '''Asp501'''
| Glu727
| <cite>Miyazaki2016</cite>
|-
| [[GH65]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}4ktr 4ktr]
| 2-O-α-glucosylglycerol phosphorylase
| ''Bacillus selenitireducens''
| isofagomine
| '''Glu475'''
| phosphate
| <cite>Touhara2014</cite>
|-
| [[GH66]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5axh 5axh]
| dextranase
| ''Thermoanaerobacter pseudethanolicus''
| isomaltohexaose
| '''Glu374'''
| Asp312
| <cite>Suzuki2016</cite>
|-
| [[GH67]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1l8n 1l8n]
| α-glucuronidase
| ''Geobacillus stearothermophilus''
| 4-O-methyl-{{Smallcaps|d}}-glucuronic acid and xylotriose
| '''Glu286'''
| Asp364 Glu392
| <cite>Golan2004</cite>
|-
| [[GH68]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1pt2 1pt2]
| levansucrase
| ''Bacillus subtilis''
| sucrose
| '''Glu342'''
| Asp86
| <cite>Meng2003</cite>
|-
| [[GH70]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3aic 3aic]
| glucansucrase
| ''Streptococcus mutans''
| α-acarbose
| '''Glu515'''
| Asp477
| <cite>Ito2011</cite>
|-
| [[GH72]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w62 2w62]
| β-1,3-glucanotransferase
| ''Saccharomyces cerevisiae'' S288C
| laminaripentaose
| '''Glu176'''
| Glu275
| <cite>Hurtado-Gerrero2009</cite>
|-
| [[GH74]]
| none
| 7-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}2ebs 2ebs]
| cellobiohydrolase (OXG-RCBH)
| ''Geotrichum sp.'' m128
| xyloglucan heptasaccharide
| '''Asp465'''
| Asp35
| <cite>Yaoi2007</cite>
|-
| [[GH76]]
| none
| (α/α)6
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5agd 5agd]
| endo-α-1,6-mannanase
| ''Bacillus circulans''
| α-1,6-mannopentaose
| '''Asp125'''
| Asp124
| <cite>Thompson2015</cite>
|-
| [[GH77]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2oww 2oww]
| 4-α-glucanotransferase
| ''Thermus thermofilus''
| acarbose + 4-deoxy-α-{{Smallcaps|d}}-glucose
| '''Glu340'''
| Asp293
| <cite>Barends2007</cite>
|-
| [[GH78]]
| H
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3w5n 3w5n]
| α-{{Smallcaps|l}}-rhamnosidase
| ''Streptomyces avermitilis''
| {{Smallcaps|l}}-rhamnose
| '''Glu636'''
| Glu895
| <cite>Fujimoto2013</cite>
|-
| [[GH79]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5e9c 5e9c]
| heparanase
| ''Homo sapiens''
| heparin tetrasaccharide
| '''Glu225'''
| Glu343
| <cite>Wu2015</cite>
|-
| [[GH80]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH24''
|
|
|
|
|
|
|-
| [[GH81]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5t4g 5t4g]
| endo-β-1,3-glucanase
| ''Bacillus halodurans'' C-125
| laminarin
| '''Asp466'''
| Glu542
| <cite>Pluvinage2017</cite>
|-
| [[GH83]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1z4x 1z4x]
| hemagglutinin-neuraminidase
| Simian virus 5
| α-2,3-sialyllactose
| '''Glu247''' relay
| Tyr523
| <cite>Yuan2005</cite>
|-
| [[GH84]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2chn 2chn]
| β-''N''-acetyl-glucosaminidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| NAG-thiazoline
| '''Glu242'''
| internal
| <cite>Dennis2006</cite>
|-
| [[GH85]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w92 2w92]
| endo-β-''N''-acetyl-glucosaminidase D
| ''Streptococcus pneumoniae'' TIGR4
| NAG-thiazoline
| '''Glu337'''
| internal
| <cite>Abbott2009</cite>
|-
| [[GH86]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4aw7 4aw7]
| β-porphyranase
| ''Bacteroides plebeius''
| porphyran fragment
| '''Glu152'''
| Glu279
| <cite>Hehemann_1_2012</cite>
|-
| [[GH89]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vcb 2vcb]
| α-''N''-acetyl-glucosaminidase
| ''Clostridium perfringens''
| PUGNAc
| '''Glu483'''
| Glu601
| <cite>Ficko-Blean2008</cite>
|-
| [[GH92]]
| none
| (α/α)6 and β-sandwich
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ww1 2ww1]
| α-1,2-mannosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| thiomannobioside
| '''Glu533'''
| Asp644 Asp642
| <cite>Zhu2009</cite>
|-
| [[GH93]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3a72 3a72]
| exo-arabinanase
| ''Penicillium chrysogenum''
| arabinobiose
| '''Glu246'''
| Glu174
| <cite>Sogabe2011</cite>
|-
| [[GH94]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4zli 4zli]
| cellobionic acid phosphorylase
| ''Saccharophagus degradans''
| 3-O-β-{{Smallcaps|d}}-glucopyranosyl-α-{{Smallcaps|d}}-glucopyranuronic acid
| '''Asp472'''
| phosphate
| <cite>Nam2015</cite>
|-
| [[GH95]]
| none
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ead 2ead]
| α-1,2-{{Smallcaps|l}}-fucosidase
| ''Bifidobacterium bifidum''
| Fuc-α-1,2-Gal
| '''Glu566'''
| Asn423 Asp766
| <cite>Nagae2007</cite>
|-
| [[GH97]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining + inverting
| '''''anti'''''
| [{{PDBlink}}2zq0 2zq0]
| α-glucosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| acarbose
| '''Glu532'''
| Glu508
| <cite>Kitamura2008</cite>
|-
| [[GH98]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2wmg 2wmg]
| endo-β-1,4-galactosidase
| ''Streptococcus pneumoniae''
| A-LewisY pentasaccharide
| '''Glu158'''
| Asp251 Glu301
| <cite>Higgins2009</cite>
|-
| [[GH99]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ad4 4ad4]
| endo-α-mannosidase
| ''Bacteroides xylanisolvens''
| glucose-1,3-isofagomine and α-1,2- mannobiose
| '''Glu336'''
| debated
| <cite>Thompson2012</cite>
|-
| [[GH100]]
| none
| (α/α)6 core
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5gop 5gop]
| invertase
| ''Anabaena (Nostoc) sp.'' pcc7120
| sucrose
| '''Asp188'''
| Glu414
| <cite>Xie2016</cite>
|-
| [[GH102]]
| none
| double-ψ β-barrel
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}2pi8 2pi8]
| lytic transglycosylase A
| ''Escherichia coli''
| chitohexaose
| '''Asp308'''
| none
| <cite>van_Straaten2007</cite>
|-
| [[GH103]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1d0k 1d0k]
| lytic transglycosylase SLT35
| ''Escherichia coli''
| murodipeptides
| '''Glu162'''
| internal
| <cite>van_Asselt2000</cite>
|-
| [[GH106]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5mwk 5mwk]
| α-{{Smallcaps|l}}-rhamnosidase BT_0986
| ''Bacteroides thetaiotaomicron''
| pectin heptasaccharide
| '''Glu461'''
| Glu593 or Glu561
| <cite>Ndeh2017</cite>
|-
| [[GH107]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| ''predicted syn by clan''
| ''see at GH29''
|
|
|
|
|
|
|-
| [[GH110]]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}7jwf 7jwf]
| α-1,3-galactosidase
| ''Pseudoalteromonas distincta''
| Gal-α1,3-Gal
| '''Asp344'''
| Asp321 Asp345
| <cite>McGuire2020</cite>
|-
| [[GH113]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4cd8 4cd8]
| β-mannanase
| ''Alicyclobacillus acidocaldarius''
| mannobioimidazole
| '''Glu151'''
| Glu231
| <cite>Williams2014</cite>
|-
| [[GH116]]
| O
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at GH52''
|
|
|
|
|
|
|-
| [[GH117]]
| none
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}4ak7 4ak7]
| α-1,3-3,6-anhydro-{{Smallcaps|l}}-galactosidase
| ''Bacteroides plebeius''
| neoagarobiose
| '''His302''' (relay from Asp320)
| Asp90
| <cite>Hehemann_2_2012</cite>
|-
| [[GH120]]
| none
| parallel β-helix and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3vsv 3vsv]
| β-xylosidase XylC
| ''Thermoanaerobacterium saccharolyticum'' JW/SL-YS485
| {{Smallcaps|d}}-xylose
| '''Glu405'''
| Asp382
| <cite>Huang2012</cite>
|-
| [[GH123]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5fr0 5fr0]
| exo-β-N-acetyl-galactosaminidase
| ''Clostridium perfringens''
| ''N''-difluoroacetyl-{{Smallcaps|d}}-galactosamine
| '''Glu345'''
| internal
| <cite>Noach2016</cite>
|-
| [[GH125]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5m7y 5m7y]
| exo-α-1,6-mannosidase
| ''Clostridium perfringens''
| 1,6-α-mannotriose
| '''Asp220'''
| Glu393
| <cite>Alonso-Gil2016</cite>
|-
| [[GH127]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3wrg 3wrg]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bifidobacterium longum''
| {{Smallcaps|l}}-arabinose
| '''Glu322'''
| Cys417
| <cite>Huang2014</cite>
|-
| [[GH128]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}6ufl 6ufl]
| β-1,3-glucanase
| ''Amycolatopsis mediterranei''
| laminarihexaose
| '''Glu102'''
| Glu199
| <cite>Santos2020</cite>
|-
| [[GH130]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5b0s 5b0s]
| β-1,2-mannobiose phosphorylase
| ''Listeria innocua''
| β-1,2-mannotriose
| '''Asp141''' relay
| phosphate
| <cite>Tsuda2015</cite>
|-
| [[GH134]]
| none
| β + α
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5jug 5jug]
| β-mannanase
| ''Streptomyces sp.''
| mannopentaose
| '''Glu45'''
| Asp57
| <cite>Jin2016</cite>
|-
| [[GH136]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}5gqf 5gqf]
| lacto-N-biosidase
| ''Bifidobacterium longum''
| lacto-N-biose
| '''Asp411'''
| Asp418
| <cite>Yamada2017</cite>
|-
| [[GH137]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|l}}
| unknown
| '''''anti'''''
| [{{PDBlink}}5mui 5mui]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0996
| ''Bacteroides thetaiotaomicron''
| pectin oligosaccharide
| '''Glu240'''
| Glu159
| <cite>Ndeh2017</cite>
|-
| [[GH138]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}6hzg 6hzg]
| α-1,2-{{Smallcaps|d}}-galacturonidase
| ''Bacteroides paurosaccharolyticus''
| alpha-{{Smallcaps|d}}-galactopyranuronic
| '''Glu294'''
| Glu361
| <cite>Labourel2019</cite>
|-
| [[GH146]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5opj 5opj]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0349
| ''Bacteroides thetaiotaomicron''
| {{Smallcaps|l}}-arabinose
| '''Glu320'''
| Cys416
| <cite>Luis2018</cite>
|-
| [[GH147]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH148]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH149]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH156]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}6s0e 6s0e]
| exo-α-sialidase
| uncultured bacterium pG7
| N-acetyl-2,3-dehydro-2-deoxyneuraminic acid
| '''His134''' (relay from Asp132)
| Asp14
| <cite>Bule2019</cite>
|-
| [[GH157]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH158]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH161]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH162]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}6imw 6imw]
| endo-β-1,2-glucanase
| ''Talaromyces funiculosus''
| beta-1,2-glucan
| '''Glu262''' via C3-OH of glc at subs. +2
| Asp446
| <cite>Tanaka2019</cite>
|-
| [[GH164]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}6t75 6t75]
| β-mannosidase
| ''Bacteroides salyersiae''
| 2-deoxy-2-F-mannosyl
| '''Glu160'''
| Glu297
| <cite>Armstrong2020</cite>
|-
| [[GH172]]
| none
| β-jelly roll
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}7v1w 7v1w]
| difructose-anhydride synthase
| ''Bifidobacterium dentum''
| beta-{{Smallcaps|d}}-arabinofuranose
| '''Glu270'''
| Glu291
| <cite>Kashima2021</cite>
|-
| [[GH181]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}8axi 8axi]
| exo-α-sialidase
| ''Akkermansia muciniphila''
| 2-deoxy-2,3-dehydro-''N''-acetyl-neuraminic acid + T-antigen disaccharide
| '''Asp345'''
| Glu218
| <cite>Shuoker2023</cite>
|-
| [[GH183]]
| none
| 5-bladed β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}8ic1 8ic1]
| endo-α-1,5-{{Smallcaps|d}}-arabinofuranosidase
| ''Microbacterium arabinogalactanolyticum'' JCM 9171
| α-{{Smallcaps|d}}-Araf-(1,5)-α-{{Smallcaps|d}}-Araf-(1,5)-α-{{Smallcaps|d}}-Araf-(1,5)-α-{{Smallcaps|d}}-Araf
| '''Asp51'''
| Asp33
| <cite>Shimokawa2023</cite>
|-
| [[GH186]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}8ip1 8ip1]
| β-1,2-glucanase
| ''Escherechia coli''
| β-1,2-glucan
| '''Asp388'''
| Asp300 + 2 waters
| <cite>Motouchi2023</cite>
|-
| [http://www.cazy.org/GH0.html n.c.*]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2vjj 2vjj]
| endo-α-N-acetylglucosaminidase
| Bacteriophage HK620
| O18A1 O-antigen hexasaccharide
| '''Asp339'''
| Glu372
| <cite>Barbirz2008</cite>
|}
<nowiki>*</nowiki> n.c.: Found among the collection of [http://www.cazy.org/GH0.html non-classified GH sequences in the CAZy Database].

== References ==

<biblio>
# HeightmanVasella1999 Heightman TD and Vasella AT. ''Recent Insights into Inhibition, Structure, and Mechanism of Configuration-Retaining Glycosidases.'' Angew Chem Int Ed. 1999 38(6):750-770. [http://www3.interscience.wiley.com/journal/55000581/abstract Article online].
# Nerinckx2005 pmid=15642336
# Wu2012 pmid=23137336
# Perez1978 Pérez S and Marchessault RH. ''The exo-anomeric effect: experimental evidence from crystal structures.'' Carbohydr res. 1978 65:114-120. [http://dx.doi.org/10.1016/S0008-6215(00)84218-4 DOI:10.1016/S0008-6215(00)84218-4]
# Cramer1997 Cramer CJ, Truhlar DG, and French AD. ''Exo-anomeric effects on energies and geometries of different conformations of glucose and related systems in the gas phase and aqueous solution.'' Carbohydr res. 1997 298:1-14. [http://dx.doi.org/10.1016/S0008-6215(96)00297-2 DOI:10.1016/S0008-6215(96)00297-2]
# Johnson2009 pmid=19733839
# Alonso2016 pmid=26889578
# Gloster2006 pmid=17002288
# van_Bueren2009 pmid=18976664
# Hrmova2001 pmid=11709165
# Rajan2004 pmid=15341727
# Varrot2003 pmid=12595701
# Zhou1999 pmid=10508787
# Sulzenbacher1999 pmid=10200171
# Urbanikova2011 pmid=21501386
# Guerin2002 pmid=11884144
# Schubot2004 pmid=14756552
# Suzuki2009 pmid=19279191
# Wan2014 pmid=24419374
# Sandgren2004 pmid=15364577
# Uitdehaag1999 pmid=10331869
# Miyake2003 pmid=12741813
# Harris1993 pmid=8431441
# Allouch2004 pmid=15062085
# Wojtkowiak2013 pmid=23275163
# Papanikolau2001 pmid=11560481
# Prag2000 pmid=10884356
# Vocadlo2001 pmid=11518970
# Karlsen1996 pmid=15299731
# Baldwin1993 pmid=8259514
# Cartmell2008 pmid=18799462
# Fernandez-Leiro2010 pmid=20592022
# Abbott2007 pmid=17397864
# Sakurama2012 pmid=22451675
# Sim2008 pmid=18036614
# Verhaest2007 pmid=17335500
# Amaya2004 pmid=15130470
# Zhu2012 pmid=23015718
# Maksimainen2011 pmid=21130883
# Merceron2012 pmid=23012371
# Gibson2007 pmid=17455176
# Shah2008 pmid=18599462
# Czjzek2005 pmid=16212978
# Godoy2016 pmid=27685756
# Fujimoto2010 pmid=20739278
# Kitago2007 pmid=17905739
# Davies1996 pmid=15299721
# Lyu2014 pmid=24766439
# Karaveg2005 pmid=15713668
# Nerinckx2008 pmid=18619586
# Pluvinage2013 pmid=23921382
# Yuan2005 pmid=15893670
# Hoevel2003 pmid=14517232
# Espina2014 pmid=24816105
# Le_Nours2009 pmid=19089956
# Miyanaga2004 pmid=15292273
# Bianchetti2015 pmid=25752603
# Markovic-Housley2000 pmid=11080624
# Imamura2003 pmid=12618437
# Hill2013 pmid=24297913
# Maehara2014 pmid=24482228
# Miyazaki2016 pmid=27688023
# Touhara2014 pmid=24828502
# Suzuki2016 pmid=26494689
# Golan2004 pmid=14573597
# Meng2003 pmid=14517548
# Ito2011 pmid=21354427
# Hurtado-Gerrero2009 pmid=19097997
# Yaoi2007 pmid=17498741
# Thompson2015 pmid=25772148
# Barends2007 pmid=17420245
# Fujimoto2013 pmid=23486481
# Wu2015 pmid=26575439
# Pluvinage2017 pmid=28781080
# Dennis2006 pmid=16565725
# Abbott2009 pmid=19181667
# Hehemann_1_2012 pmid=23150581
# Ficko-Blean2008 pmid=18443291
# Zhu2009 pmid=20081828
# Sogabe2011 pmid=21543843
# Nam2015 pmid=26041776
# Nagae2007 pmid=17459873
# Kitamura2008 pmid=18981178
# Higgins2009 pmid=19608744
# van_Straaten2007 pmid=17502382
# van_Asselt2000 pmid=10684641
# Ndeh2017 pmid=28329766
# Labourel2019 pmid=30877196
# Luis2018 pmid=29255254
# Bule2019 pmid=31645552
# Jin2016 Jin Y, Petricevic M, John A, Raich L, Jenkins H, Portela De Souza L, Cuskin F, Gilbert HJ, Rovira C, Goddard-Borger ED, Williams SJ, and Davies GJ. ''A β-Mannanase with a Lysozyme-like Fold and a Novel Molecular Catalytic Mechanism.'' ACS Cent Sci. 2016 Nov [http://dx.doi.org/10.1021/acscentsci.6b00232 DOI:10.1021/acscentsci.6b00232]
# Yamada2017 pmid=28392148
# Ohnuma2014 pmid=24582745
# Thompson2012 pmid=22219371
# Xie2016 pmid=27777307
# Williams2014 pmid=24339341
# Hehemann_2_2012 pmid=22393053
# Huang2012 pmid=22992047
# Noach2016 pmid=27038508
# Alonso-Gil2016 pmid=28026180
# Huang2014 Huang CH, Zhu Z, Cheng YS, Chan HC, Ko TP, Chen CC, Wang I, Ho MR, Hsu ST, Zeng YF, Huang YN, Liu JR, Guo RT. ''Structure and Catalytic Mechanism of a Glycoside Hydrolase Family-127 β-L-Arabinofuranosidase (HypBA1).'' J Bioprocess Biotech. 2014 4:171 [http://dx.doi.org/10.4172/2155-9821.1000171 DOI:10.4172/2155-9821.1000171]
# Tsuda2015 pmid=26632508
# Barbirz2008 pmid=18547389
# Tanaka2019 pmid=30926603
# Armstrong2020 pmid=31871050
# Santos2020 pmid=32451508
# Kashima2021 pmid=34688653
# McGuire2020 pmid=33127644
# Shuoker2023 pmid=37005422
# Shimokawa2023 pmid=37726269
# Motouchi2023 pmid=37735577

</biblio>
[[Category:Definitions and explanations]]

Syn/anti lateral protonation

2023-10-26T07:29:21Z

Wim Nerinckx: Added GH183 anti protonator

{{CuratorApproved}}
* [[Author]]: [[User:Wim Nerinckx|Wim Nerinckx]]
* [[Responsible Curator]]: [[User:Spencer Williams|Spencer Williams]]

----

== Overview ==

This page provides a table that summarizes the spatial positioning of the catalytic [[general acid]] residue in the active sites of [[glycoside hydrolase]]s, relative to the substrate. The table below updates those found in the seminal paper on this concept by Heightman and Vasella <cite>HeightmanVasella1999</cite>, and a following paper by Nerinckx ''et al.'' <cite>Nerinckx2005</cite>.

== Background ==

The ''"not from above, but from the side"'' concept of semi-lateral glycosidic oxygen [[General_acid/base|protonation]] by [[glycoside hydrolase]]s was introduced by Heightman and Vasella <cite>HeightmanVasella1999</cite>. It was originally only described for [[Anomeric centre (alpha and beta)|beta]]-equatorial [[glycoside hydrolase]]s, but appears to be equally applicable to enzymes acting on an [[Anomeric centre (alpha and beta)|alpha]]-axial glycosidic bond <cite>Nerinckx2005</cite>. When dividing [[Sub-site nomenclature|subsite -1]] into half-spaces by a plane defined by the glycosidic oxygen and C1' and H1' of the –1 glycoside, many ligand-complexed structures reveal that the [[General_acid/base|proton donor]] is positioned either in the ''syn'' half-space (near the ring-oxygen of the –1 glycoside), or in the ''anti'' half-space (on the opposite side of the ring-oxygen). Members of the same GH [[Families|family]] appear to share a common ''syn'' or ''anti'' [[General_acid/base|protonator]] arrangement and further, this specificity appears to be preserved within [[Clans|Clans]] of [[Families|families]]. This page's compilation of [[Sub-site nomenclature|subsite -1]] occupied complexes shows that about 70% of all GH [[Families|families]] are ''anti'' [[General_acid/base|protonators]].

Closer inspection of crystal structures of [[Sub-site nomenclature|–1/+1 subsite]]-spanning substrates, or substrate-analogue ligands, in complex with enzymes reveals a further intriguing corollary <cite>Nerinckx2005 Wu2012</cite>. In substrate-bound complexes with ''anti'' [[General_acid/base|protonating]] GH enzymes, the scissile [[Anomeric centre (alpha and beta)|anomeric bond]] (often studied using the thio-analogue) shows a dihedral angle φ (O5'-C1'-[O,S]x-Cx) that is in the lowest-energy synclinal (gauche) conformation. The rationale for this is that a minus synclinal dihedral angle φ for an equatorial glycosidic bond, or plus synclinal for an axial glycosidic bond <cite>Perez1978</cite>, allows for hyperconjugative overlap of the C1'-O5' antibonding orbital with an antiperiplanar-oriented lone pair orbital lobe of the glycosidic oxygen, thereby creating partial double bond character and stabilization of the glycosidic bond by 4–5 kcal/mol; this ground-state stabilizing phenomenon is known as the ‘exo-anomeric effect’ <cite>Cramer1997 Johnson2009 Alonso2016</cite>. ''Anti'' [[General_acid/base|protonation]] occurs on the glycosidic oxygen’s antiperiplanar lone pair, thereby removing the stabilizing exo-anomeric effect. This suggests that ''anti'' [[General_acid/base|protonation]] is an enzymic approach for lowering the activation barrier leading to the [[Transition state|transition state]] (Figure 1 centre).

''Syn'' [[General_acid/base|protonating]] [[glycoside hydrolase]]s apparently make use of a different approach <cite>Nerinckx2005 Wu2012</cite>. In many [[Sub-site nomenclature|–1/+1 subsite]]-spanning ligand complexes, the dihedral angle φ of the scissile anomeric bond has been rotated away from its lowest-energy synclinal position: clockwise to minus-anticlinal or antiperiplanar for beta-equatorial; counterclockwise to plus-anticlinal or antiperiplanar for alpha-axial [[Anomeric centre (alpha and beta)|anomeric bonds]]. This removes the hyperconjugative overlap and thus also the stabilizing exo-anomeric effect. And because of this rotation, a lone pair of the glycosidic oxygen is directed into the ''syn'' half-space, allowing it to be protonated by the ''syn''-positioned [[General_acid/base|proton donor]] (Figure 1 right).

[[File:Syn_anti.jpg|800px|thumb|center|Figure 1. Newman projections, with the glycosidic oxygen as proximal atom and the anomeric carbon as distal atom, showing ''anti'' (centre) versus ''syn'' (right) semi-lateral [[General_acid/base|protonation]] in beta-equatorial (top) and alpha-axial (bottom) [[glycoside hydrolase]]s. The indicated φ is the dihedral angle for O5'-C1'-O4-C4.]]

== Table of ''syn/anti'' protonation examples ==

This table contains only one example per GH [[Families|family]] of a ligand-complexed protein structure where the ''syn'' or ''anti'' positioning of the [[General_acid/base|proton donor]] can be clearly observed; other examples may be available on a [[Families|family-by-family]] basis. The reader is thus advised to consult the [http://www.cazy.org/fam/acc_GH.html#table CAZy database] for a current, comprehensive list of CAZyme structures. Where available, the selected examples are Michaelis-type complexes with the ligand spanning the [[Sub-site nomenclature|-1/+1 subsites]], since these have an intact glycosidic or thioglycosidic bond, or are ''N''-analogs of the substrate (''e.g.'' acarbose). In some examples, the [[General_acid/base|proton donor]] has been mutated (''e.g.'', to the corresponding amide or to an alanine), and in those cases one may wish to look at a superposition of the given PDB example with the structure of the native enzyme. If a Michaelis-type complex is not yet available, the second and third example choices, respectively, are trapped glycosyl-enzyme [[intermediate]]s and product complexes where [[Sub-site nomenclature|subsite -1]] is occupied.

''Please also be aware that this is a large table with many data. Please contact the page Author or Responsible Curator with corrections.''

=== Table ===
This table can be re-sorted by clicking on the icons in the header (''javascript must be turned on in your browser''). To reset the page to be sorted by GH family, click the ''View'' tab at the very top of the page.

{| {{Prettytable}} class="sortable"
|- valign="top"
! '''Family'''
! '''Clan'''
! '''Structure fold '''
! '''Anomeric specificity'''
! '''Mechanism'''
! '''''Syn/anti'' protonator'''
! '''Example PDB ID'''
! '''Enzyme'''
! '''Organism'''
! '''Ligand'''
! '''General acid'''
! '''Nucleophile or General base'''
! '''Reference'''
|-
| [[GH1]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2cer 2cer]
| β-glycosidase S
| ''Sulfolobus solfataricus'' P2
| phenethyl glucoimidazole
| '''Glu206'''
| Glu387
| <cite>Gloster2006</cite>
|-
| [[GH2]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vzu 2vzu]
| exo-β-glucosaminidase
| ''Amicolatopsis orientalis''
| PNP-β-{{Smallcaps|d}}-glucosamine
| '''Glu469'''
| Glu541
| <cite>van_Bueren2009</cite>
|-
| [[GH3]]
| none
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1iex 1iex]
| exo-1,3-1,4-glucanase
| ''Hordeum vulgare''
| thiocellobiose
| '''Glu491'''
| Asp285
| <cite>Hrmova2001</cite>
|-
| [[GH4]]
| none
| Rossmann + α6/β3 + β3/α4
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1u8x 1u8x]
| 6-P-α-glucosidase
| ''Bacillus subtilis''
| alpha-{{Smallcaps|d}}-glucose-6-phosphate
| '''Asp172'''
| not applicable
| <cite>Rajan2004</cite>
|-
| [[GH5]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1h2j 1h2j]
| endo-β-1,4-glucanase
| ''Bacillus agaradhaerens''
| 2',4'-DNP-2-F-cellobioside
| '''Glu129'''
| Glu228
| <cite>Varrot2003</cite>
|-
| [[GH6]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1qjw 1qjw]
| cellobiohydrolase 2
| ''Hypocrea jecorina''
| (Glc)2-S-(Glc)2
| '''Asp221'''
| debated
| <cite>Zhou1999</cite>
|-
| [[GH7]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1ovw 1ovw]
| endo-1,4-glucanase
| ''Fusarium oxysporum''
| thio-(Glc)5
| '''Glu202'''
| Glu197
| <cite>Sulzenbacher1999</cite>
|-
| [[GH8]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1kwf 1kwf]
| endo-1,4-glucanase
| ''Clostridium thermocellum''
| cellopentaose
| '''Glu95'''
| Asp278
| <cite>Guerin2002</cite>
|-
| [[GH9]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1rq5 1rq5]
| cellobiohydrolase
| ''Clostridium thermocellum''
| cellotetraose
| '''Glu795'''
| Asp383
| <cite>Schubot2004</cite>
|-
| [[GH10]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2d24 2d24]
| β-1,4-xylanase
| ''Streptomyces olivaceoviridis'' E-86
| xylopentaose
| '''Glu128'''
| Glu236
| <cite>Suzuki2009</cite>
|-
| [[GH11]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}4hk8 4hk8]
| endo-β-1,4-xylanase
| ''Hypocrea jecorina''
| xylohexaose
| '''Glu177'''
| Glu86
| <cite>Wan2014</cite>
|-
| [[GH12]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1w2u 1w2u]
| endoglucanase
| ''Humicola grisea''
| thiocellotetraose
| '''Glu205'''
| Glu120
| <cite>Sandgren2004</cite>
|-
| [[GH13]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1cxk 1cxk]
| β-cyclodextrin glucanotransferase
| ''Bacillus circulans''
| maltononaose
| '''Glu257'''
| Asp229
| <cite>Uitdehaag1999</cite>
|-
| [[GH14]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1itc 1itc]
| β-amylase
| ''Bacillus cereus''
| maltopentaose
| '''Glu172'''
| Glu367
| <cite>Miyake2003</cite>
|-
| [[GH15]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1dog 1dog]
| glucoamylase
| ''Aspergillus awamori''
| 1-deoxynojirimycin
| '''Glu179'''
| Glu400
| <cite>Harris1993</cite>
|-
| [[GH16]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1urx 1urx]
| β-agarase A
| ''Zobellia galactanivorans''
| oligoagarose
| '''Glu152'''
| Glu147
| <cite>Allouch2004</cite>
|-
| [[GH17]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzj 4gzj]
| endo-β-1,3-glucanase
| ''Solanum tuberosum''
| laminaratriose + laminarabiose
| '''Glu118'''
| Glu259
| <cite>Wojtkowiak2013</cite>
|-
| [[GH18]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1ffr 1ffr]
| chitinase A
| ''Serratia marcescens''
| (NAG)6
| '''Glu315'''
| internal
| <cite>Papanikolau2001</cite>
|-
| [[GH19]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}3wh1 3wh1]
| chitinase
| ''Bryum coronatum''
| (GlcNAc)4
| '''Glu61'''
| Glu70
| <cite>Ohnuma2014</cite>
|-
| [[GH20]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1c7s 1c7s]
| chitobiase
| ''Serratia marcescens''
| chitobiose
| '''Glu540'''
| internal
| <cite>Prag2000</cite>
|-
| [[GH22]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1h6m 1h6m]
| lysozyme C
| ''Gallus gallus''
| Chit-2-F-chitosyl
| '''Glu35'''
| Asp52
| <cite>Vocadlo2001</cite>
|-
| [[GH23]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1lsp 1lsp]
| lysozyme G
| ''Cygnus atratus''
| Bulgecin A
| '''Glu73'''
| internal
| <cite>Karlsen1996</cite>
|-
| [[GH24]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}148l 148l]
| lysozyme E
| Bacteriophage T4
| chitobiosyl
| '''Glu11'''
| Glu26
| <cite>Baldwin1993</cite>
|-
| [[GH26]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vx6 2vx6]
| exo-β-mannanase
| ''Cellvibrio japonicus'' Ueda107
| Gal1Man4
| '''Glu221'''
| Glu338
| <cite>Cartmell2008</cite>
|-
| [[GH27]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}} / beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3lrm 3lrm]
| α-galactosidase
| ''Saccharomyces cerevisiae''
| raffinose
| '''Asp209'''
| Asp141
| <cite>Fernandez-Leiro2010</cite>
|-
| [[GH28]]
| N
| β-helix
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}2uvf 2uvf]
| exo-polygalacturonosidase
| ''Yersinia enterocolitica'' ATCC9610D
| digalacturonic acid
| '''Asp402'''
| Asp381 Asp403
| <cite>Abbott2007</cite>
|-
| [[GH29]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| '''''syn'''''
| [{{PDBlink}}3uet 3uet]
| α-1,3/4-fucosidase
| ''Bifidobacterium longum'' subsp. infantis
| lacto-''N''-fucopentaose II
| '''Glu217'''
| Asp172
| <cite>Sakurama2012</cite>
|-
| [[GH30]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2y24 2y24]
| glucurono-xylanase
| ''Dickea chrysanthemi'' D1
| glucuronoxylan tetrasaccharide
| '''Glu163'''
| Glu253
| <cite>Urbanikova2011</cite>
|-
| [[GH31]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2qmj 2qmj]
| maltase-glucoamylase
| ''Homo sapiens''
| acarbose
| '''Asp542'''
| Asp443
| <cite>Sim2008</cite>
|-
| [[GH32]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2add 2add]
| fructan β-(2,1)-fructosidase
| ''Cichorium intybus''
| sucrose
| '''Glu201'''
| Asp22
| <cite>Verhaest2007</cite>
|-
| [[GH33]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1s0i 1s0i]
| transsialidase
| ''Trypanosoma cruzi''
| sialyllactose
| '''Asp59'''
| Tyr342
| <cite>Amaya2004</cite>
|-
| [[GH34]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzw 4gzw]
| N2 neuraminidase
| ''Influenza'' A Tanzania/205/2010 H3N2
| α-{{Smallcaps|d}}-Neup5Ac-(2,3)-β-{{Smallcaps|d}}-Galp-(1,4)-β-{{Smallcaps|d}}-GlcpNAc
| '''Asp151'''
| Tyr406
| <cite>Zhu2012</cite>
|-
| [[GH35]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3ogv 3ogv]
| β-galactosidase
| ''Hypocrea jecorina''
| 2-phenylethyl 1-thio-β-{{Smallcaps|d}}-galactopyranoside
| '''Glu200'''
| Glu298
| <cite>Maksimainen2011</cite>
|-
| [[GH36]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4fnu 4fnu]
| β-galactosidase
| ''Geobacillus stearothermophilus''
| stachyose
| '''Asp584'''
| Asp478
| <cite>Merceron2012</cite>
|-
| [[GH37]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2jf4 2jf4]
| trehalase
| ''Escherichia coli''
| validoxylamine
| '''Asp312'''
| Glu496
| <cite>Gibson2007</cite>
|-
| [[GH38]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3czn 3czn]
| Golgi α-mannosidase II
| ''Drosophila melanogaster''
| GlcNAcMan(5)GlcNAc(2)
| '''Asp341'''
| Asp204
| <cite>Shah2008</cite>
|-
| [[GH39]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2bfg 2bfg]
| β-xylosidase
| ''Geobacillus stearothermophilus''
| 2,5-dinitrophenyl-β-{{Smallcaps|d}}-xyloside
| '''Glu160'''
| Glu278
| <cite>Czjzek2005</cite>
|-
| [[GH42]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ucf 4ucf]
| β-galactosidase
| ''Bifidobacterium bifidum''
| {{Smallcaps|d}}-galactose
| '''Glu161'''
| Glu320
| <cite>Godoy2016</cite>
|-
| [[GH43]]
| F
| 5-fold β-propeller
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3akh 3akh]
| exo-1,5-α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces avermitilis''
| α-1,5-arabinofuranotriose
| '''Glu196'''
| Asp220
| <cite>Fujimoto2010</cite>
|-
| [[GH44]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2eqd 2eqd]
| endoglucanase
| ''Clostridium thermocellum''
| cellooctaose
| '''Glu186'''
| Glu359
| <cite>Kitago2007</cite>
|-
| [[GH45]]
| none
| 6-stranded β-barrel
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4eng 4eng]
| endo-1,4-glucanase
| ''Humicola insolens''
| cellohexaose
| '''Asp121'''
| Asp10
| <cite>Davies1996</cite>
|-
| [[GH46]]
| I
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4olt 4olt]
| chitosanase
| ''Microbacterium sp.'' OU01
| hexa-glucosamine
| '''Glu25'''
| Asp43
| <cite>Lyu2014</cite>
|-
| [[GH47]]
| none
| (α/α)7
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1x9d 1x9d]
| α-mannosidase I
| ''Homo sapiens''
| Me-2-S-(α-Man)-2-thio-α-Man
| '''Asp463'''
| Glu599
| <cite>Karaveg2005</cite>, <cite>Nerinckx2008</cite>
|-
| [[GH48]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH8''
|
|
|
|
|
|
|-
| [[GH49]]
| N
| β-helix
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH28''
|
|
|
|
|
|
|-
| [[GH50]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4bq5 4bq5]
| exo-β-agarase
| ''Saccharophagus degradans''
| neoagarotetraose
| '''Glu535'''
| Glu695
| <cite>Pluvinage2013</cite>
|-
| [[GH51]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1qw9 1qw9]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Geobacillus stearothermophilus''
| PNP-{{Smallcaps|l}}-arabinofuranoside
| '''Glu175'''
| Glu294
| <cite>Hoevel2003</cite>
|-
| [[GH52]]
| O
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4c1p 4c1p]
| β-xylosidase
| ''Geobacillus thermoglucosidasius''
| xylobiose
| '''Asp517'''
| Glu537
| <cite>Espina2014</cite>
|-
| [[GH53]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2ccr 2ccr]
| β-1,4-galactanase
| ''Bacillus licheniformis''
| galactotriose
| '''Glu165'''
| Glu263
| <cite>Le_Nours2009</cite>
|-
| [[GH54]]
| none
| β-sandwich
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1wd4 1wd4]
| α-{{Smallcaps|l}}-arabinofuranosidase B
| ''Aspergillus kawachii''
| {{Smallcaps|l}}-arabinofuranose
| '''Asp297'''
| Glu221
| <cite>Miyanaga2004</cite>
|-
| [[GH55]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4tz5 4tz5]
| exo-β-1,3-glucanase
| ''Streptomyces sp.'' SirexAA-E
| laminarihexaose
| '''Glu502'''
| unknown
| <cite>Bianchetti2015</cite>
|-
| [[GH56]]
| none
| (β/α)7
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1fcv 1fcv]
| hyaluronidase
| ''Apis mellifera''
| (hyaluron.)4
| '''Glu113'''
| internal
| <cite>Markovic-Housley2000</cite>
|-
| [[GH57]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1k1y 1k1y]
| glucanotransferase
| ''Thermococcus litoralis''
| acarbose
| '''Asp214'''
| Glu123
| <cite>Imamura2003</cite>
|-
| [[GH59]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ccc 4ccc]
| β-galactocerebrosidase
| ''Mus musculus''
| PNP-β-{{Smallcaps|d}}-galactoside
| '''Glu182'''
| Glu258
| <cite>Hill2013</cite>
|-
| [[GH62]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3wn0 3wn0]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces coelicolor''
| β-{{Smallcaps|l}}-Arabinofuranose
| '''Glu361'''
| Asp202
| <cite>Maehara2014</cite>
|-
| [[GH63]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5ca3 5ca3]
| α-glucosidase
| ''Escherichia coli''
| glucose and lactose
| '''Asp501'''
| Glu727
| <cite>Miyazaki2016</cite>
|-
| [[GH65]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}4ktr 4ktr]
| 2-O-α-glucosylglycerol phosphorylase
| ''Bacillus selenitireducens''
| isofagomine
| '''Glu475'''
| phosphate
| <cite>Touhara2014</cite>
|-
| [[GH66]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5axh 5axh]
| dextranase
| ''Thermoanaerobacter pseudethanolicus''
| isomaltohexaose
| '''Glu374'''
| Asp312
| <cite>Suzuki2016</cite>
|-
| [[GH67]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1l8n 1l8n]
| α-glucuronidase
| ''Geobacillus stearothermophilus''
| 4-O-methyl-{{Smallcaps|d}}-glucuronic acid and xylotriose
| '''Glu286'''
| Asp364 Glu392
| <cite>Golan2004</cite>
|-
| [[GH68]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1pt2 1pt2]
| levansucrase
| ''Bacillus subtilis''
| sucrose
| '''Glu342'''
| Asp86
| <cite>Meng2003</cite>
|-
| [[GH70]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3aic 3aic]
| glucansucrase
| ''Streptococcus mutans''
| α-acarbose
| '''Glu515'''
| Asp477
| <cite>Ito2011</cite>
|-
| [[GH72]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w62 2w62]
| β-1,3-glucanotransferase
| ''Saccharomyces cerevisiae'' S288C
| laminaripentaose
| '''Glu176'''
| Glu275
| <cite>Hurtado-Gerrero2009</cite>
|-
| [[GH74]]
| none
| 7-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}2ebs 2ebs]
| cellobiohydrolase (OXG-RCBH)
| ''Geotrichum sp.'' m128
| xyloglucan heptasaccharide
| '''Asp465'''
| Asp35
| <cite>Yaoi2007</cite>
|-
| [[GH76]]
| none
| (α/α)6
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5agd 5agd]
| endo-α-1,6-mannanase
| ''Bacillus circulans''
| α-1,6-mannopentaose
| '''Asp125'''
| Asp124
| <cite>Thompson2015</cite>
|-
| [[GH77]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2oww 2oww]
| 4-α-glucanotransferase
| ''Thermus thermofilus''
| acarbose + 4-deoxy-α-{{Smallcaps|d}}-glucose
| '''Glu340'''
| Asp293
| <cite>Barends2007</cite>
|-
| [[GH78]]
| H
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3w5n 3w5n]
| α-{{Smallcaps|l}}-rhamnosidase
| ''Streptomyces avermitilis''
| {{Smallcaps|l}}-rhamnose
| '''Glu636'''
| Glu895
| <cite>Fujimoto2013</cite>
|-
| [[GH79]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5e9c 5e9c]
| heparanase
| ''Homo sapiens''
| heparin tetrasaccharide
| '''Glu225'''
| Glu343
| <cite>Wu2015</cite>
|-
| [[GH80]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH24''
|
|
|
|
|
|
|-
| [[GH81]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5t4g 5t4g]
| endo-β-1,3-glucanase
| ''Bacillus halodurans'' C-125
| laminarin
| '''Asp466'''
| Glu542
| <cite>Pluvinage2017</cite>
|-
| [[GH83]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1z4x 1z4x]
| hemagglutinin-neuraminidase
| Simian virus 5
| α-2,3-sialyllactose
| '''Glu247''' relay
| Tyr523
| <cite>Yuan2005</cite>
|-
| [[GH84]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2chn 2chn]
| β-''N''-acetyl-glucosaminidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| NAG-thiazoline
| '''Glu242'''
| internal
| <cite>Dennis2006</cite>
|-
| [[GH85]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w92 2w92]
| endo-β-''N''-acetyl-glucosaminidase D
| ''Streptococcus pneumoniae'' TIGR4
| NAG-thiazoline
| '''Glu337'''
| internal
| <cite>Abbott2009</cite>
|-
| [[GH86]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4aw7 4aw7]
| β-porphyranase
| ''Bacteroides plebeius''
| porphyran fragment
| '''Glu152'''
| Glu279
| <cite>Hehemann_1_2012</cite>
|-
| [[GH89]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vcb 2vcb]
| α-''N''-acetyl-glucosaminidase
| ''Clostridium perfringens''
| PUGNAc
| '''Glu483'''
| Glu601
| <cite>Ficko-Blean2008</cite>
|-
| [[GH92]]
| none
| (α/α)6 and β-sandwich
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ww1 2ww1]
| α-1,2-mannosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| thiomannobioside
| '''Glu533'''
| Asp644 Asp642
| <cite>Zhu2009</cite>
|-
| [[GH93]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3a72 3a72]
| exo-arabinanase
| ''Penicillium chrysogenum''
| arabinobiose
| '''Glu246'''
| Glu174
| <cite>Sogabe2011</cite>
|-
| [[GH94]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4zli 4zli]
| cellobionic acid phosphorylase
| ''Saccharophagus degradans''
| 3-O-β-{{Smallcaps|d}}-glucopyranosyl-α-{{Smallcaps|d}}-glucopyranuronic acid
| '''Asp472'''
| phosphate
| <cite>Nam2015</cite>
|-
| [[GH95]]
| none
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ead 2ead]
| α-1,2-{{Smallcaps|l}}-fucosidase
| ''Bifidobacterium bifidum''
| Fuc-α-1,2-Gal
| '''Glu566'''
| Asn423 Asp766
| <cite>Nagae2007</cite>
|-
| [[GH97]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining + inverting
| '''''anti'''''
| [{{PDBlink}}2zq0 2zq0]
| α-glucosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| acarbose
| '''Glu532'''
| Glu508
| <cite>Kitamura2008</cite>
|-
| [[GH98]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2wmg 2wmg]
| endo-β-1,4-galactosidase
| ''Streptococcus pneumoniae''
| A-LewisY pentasaccharide
| '''Glu158'''
| Asp251 Glu301
| <cite>Higgins2009</cite>
|-
| [[GH99]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ad4 4ad4]
| endo-α-mannosidase
| ''Bacteroides xylanisolvens''
| glucose-1,3-isofagomine and α-1,2- mannobiose
| '''Glu336'''
| debated
| <cite>Thompson2012</cite>
|-
| [[GH100]]
| none
| (α/α)6 core
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5gop 5gop]
| invertase
| ''Anabaena (Nostoc) sp.'' pcc7120
| sucrose
| '''Asp188'''
| Glu414
| <cite>Xie2016</cite>
|-
| [[GH102]]
| none
| double-ψ β-barrel
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}2pi8 2pi8]
| lytic transglycosylase A
| ''Escherichia coli''
| chitohexaose
| '''Asp308'''
| none
| <cite>van_Straaten2007</cite>
|-
| [[GH103]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1d0k 1d0k]
| lytic transglycosylase SLT35
| ''Escherichia coli''
| murodipeptides
| '''Glu162'''
| internal
| <cite>van_Asselt2000</cite>
|-
| [[GH106]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5mwk 5mwk]
| α-{{Smallcaps|l}}-rhamnosidase BT_0986
| ''Bacteroides thetaiotaomicron''
| pectin heptasaccharide
| '''Glu461'''
| Glu593 or Glu561
| <cite>Ndeh2017</cite>
|-
| [[GH107]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| ''predicted syn by clan''
| ''see at GH29''
|
|
|
|
|
|
|-
| [[GH110]]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}7jwf 7jwf]
| α-1,3-galactosidase
| ''Pseudoalteromonas distincta''
| Gal-α1,3-Gal
| '''Asp344'''
| Asp321 Asp345
| <cite>McGuire2020</cite>
|-
| [[GH113]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4cd8 4cd8]
| β-mannanase
| ''Alicyclobacillus acidocaldarius''
| mannobioimidazole
| '''Glu151'''
| Glu231
| <cite>Williams2014</cite>
|-
| [[GH116]]
| O
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at GH52''
|
|
|
|
|
|
|-
| [[GH117]]
| none
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}4ak7 4ak7]
| α-1,3-3,6-anhydro-{{Smallcaps|l}}-galactosidase
| ''Bacteroides plebeius''
| neoagarobiose
| '''His302''' (relay from Asp320)
| Asp90
| <cite>Hehemann_2_2012</cite>
|-
| [[GH120]]
| none
| parallel β-helix and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3vsv 3vsv]
| β-xylosidase XylC
| ''Thermoanaerobacterium saccharolyticum'' JW/SL-YS485
| {{Smallcaps|d}}-xylose
| '''Glu405'''
| Asp382
| <cite>Huang2012</cite>
|-
| [[GH123]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5fr0 5fr0]
| exo-β-N-acetyl-galactosaminidase
| ''Clostridium perfringens''
| ''N''-difluoroacetyl-{{Smallcaps|d}}-galactosamine
| '''Glu345'''
| internal
| <cite>Noach2016</cite>
|-
| [[GH125]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5m7y 5m7y]
| exo-α-1,6-mannosidase
| ''Clostridium perfringens''
| 1,6-α-mannotriose
| '''Asp220'''
| Glu393
| <cite>Alonso-Gil2016</cite>
|-
| [[GH127]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3wrg 3wrg]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bifidobacterium longum''
| {{Smallcaps|l}}-arabinose
| '''Glu322'''
| Cys417
| <cite>Huang2014</cite>
|-
| [[GH128]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}6ufl 6ufl]
| β-1,3-glucanase
| ''Amycolatopsis mediterranei''
| laminarihexaose
| '''Glu102'''
| Glu199
| <cite>Santos2020</cite>
|-
| [[GH130]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5b0s 5b0s]
| β-1,2-mannobiose phosphorylase
| ''Listeria innocua''
| β-1,2-mannotriose
| '''Asp141''' relay
| phosphate
| <cite>Tsuda2015</cite>
|-
| [[GH134]]
| none
| β + α
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5jug 5jug]
| β-mannanase
| ''Streptomyces sp.''
| mannopentaose
| '''Glu45'''
| Asp57
| <cite>Jin2016</cite>
|-
| [[GH136]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}5gqf 5gqf]
| lacto-N-biosidase
| ''Bifidobacterium longum''
| lacto-N-biose
| '''Asp411'''
| Asp418
| <cite>Yamada2017</cite>
|-
| [[GH137]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|l}}
| unknown
| '''''anti'''''
| [{{PDBlink}}5mui 5mui]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0996
| ''Bacteroides thetaiotaomicron''
| pectin oligosaccharide
| '''Glu240'''
| Glu159
| <cite>Ndeh2017</cite>
|-
| [[GH138]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}6hzg 6hzg]
| α-1,2-{{Smallcaps|d}}-galacturonidase
| ''Bacteroides paurosaccharolyticus''
| alpha-{{Smallcaps|d}}-galactopyranuronic
| '''Glu294'''
| Glu361
| <cite>Labourel2019</cite>
|-
| [[GH146]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5opj 5opj]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0349
| ''Bacteroides thetaiotaomicron''
| {{Smallcaps|l}}-arabinose
| '''Glu320'''
| Cys416
| <cite>Luis2018</cite>
|-
| [[GH147]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH148]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH149]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH156]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}6s0e 6s0e]
| exo-α-sialidase
| uncultured bacterium pG7
| N-acetyl-2,3-dehydro-2-deoxyneuraminic acid
| '''His134''' (relay from Asp132)
| Asp14
| <cite>Bule2019</cite>
|-
| [[GH157]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH158]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH161]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH162]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}6imw 6imw]
| endo-β-1,2-glucanase
| ''Talaromyces funiculosus''
| beta-1,2-glucan
| '''Glu262''' via C3-OH of glc at subs. +2
| Asp446
| <cite>Tanaka2019</cite>
|-
| [[GH164]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}6t75 6t75]
| β-mannosidase
| ''Bacteroides salyersiae''
| 2-deoxy-2-F-mannosyl
| '''Glu160'''
| Glu297
| <cite>Armstrong2020</cite>
|-
| [[GH172]]
| none
| β-jelly roll
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}7v1w 7v1w]
| difructose-anhydride synthase
| ''Bifidobacterium dentum''
| beta-{{Smallcaps|d}}-arabinofuranose
| '''Glu270'''
| Glu291
| <cite>Kashima2021</cite>
|-
| [[GH181]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}8axi 8axi]
| exo-α-sialidase
| ''Akkermansia muciniphila''
| 2-deoxy-2,3-dehydro-''N''-acetyl-neuraminic acid + T-antigen disaccharide
| '''Asp345'''
| Glu218
| <cite>Shuoker2023</cite>
|-
| [[GH183]]
| none
| 5-bladed β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}8ic1 8ic1]
| endo-α-1,5-{{Smallcaps|d}}-arabinofuranosidase
| ''Microbacterium arabinogalactanolyticum'' JCM 9171
| α-{{Smallcaps|d}}-Araf-(1,5)-α-{{Smallcaps|d}}-Araf-(1,5)-α-{{Smallcaps|d}}-Araf-(1,5)-α-{{Smallcaps|d}}-Araf
| '''Asp51'''
| Asp33
| <cite>Shimokawa2023</cite>
|-
| [http://www.cazy.org/GH0.html n.c.*]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2vjj 2vjj]
| endo-α-N-acetylglucosaminidase
| Bacteriophage HK620
| O18A1 O-antigen hexasaccharide
| '''Asp339'''
| Glu372
| <cite>Barbirz2008</cite>
|}
<nowiki>*</nowiki> n.c.: Found among the collection of [http://www.cazy.org/GH0.html non-classified GH sequences in the CAZy Database].

== References ==

<biblio>
# HeightmanVasella1999 Heightman TD and Vasella AT. ''Recent Insights into Inhibition, Structure, and Mechanism of Configuration-Retaining Glycosidases.'' Angew Chem Int Ed. 1999 38(6):750-770. [http://www3.interscience.wiley.com/journal/55000581/abstract Article online].
# Nerinckx2005 pmid=15642336
# Wu2012 pmid=23137336
# Perez1978 Pérez S and Marchessault RH. ''The exo-anomeric effect: experimental evidence from crystal structures.'' Carbohydr res. 1978 65:114-120. [http://dx.doi.org/10.1016/S0008-6215(00)84218-4 DOI:10.1016/S0008-6215(00)84218-4]
# Cramer1997 Cramer CJ, Truhlar DG, and French AD. ''Exo-anomeric effects on energies and geometries of different conformations of glucose and related systems in the gas phase and aqueous solution.'' Carbohydr res. 1997 298:1-14. [http://dx.doi.org/10.1016/S0008-6215(96)00297-2 DOI:10.1016/S0008-6215(96)00297-2]
# Johnson2009 pmid=19733839
# Alonso2016 pmid=26889578
# Gloster2006 pmid=17002288
# van_Bueren2009 pmid=18976664
# Hrmova2001 pmid=11709165
# Rajan2004 pmid=15341727
# Varrot2003 pmid=12595701
# Zhou1999 pmid=10508787
# Sulzenbacher1999 pmid=10200171
# Urbanikova2011 pmid=21501386
# Guerin2002 pmid=11884144
# Schubot2004 pmid=14756552
# Suzuki2009 pmid=19279191
# Wan2014 pmid=24419374
# Sandgren2004 pmid=15364577
# Uitdehaag1999 pmid=10331869
# Miyake2003 pmid=12741813
# Harris1993 pmid=8431441
# Allouch2004 pmid=15062085
# Wojtkowiak2013 pmid=23275163
# Papanikolau2001 pmid=11560481
# Prag2000 pmid=10884356
# Vocadlo2001 pmid=11518970
# Karlsen1996 pmid=15299731
# Baldwin1993 pmid=8259514
# Cartmell2008 pmid=18799462
# Fernandez-Leiro2010 pmid=20592022
# Abbott2007 pmid=17397864
# Sakurama2012 pmid=22451675
# Sim2008 pmid=18036614
# Verhaest2007 pmid=17335500
# Amaya2004 pmid=15130470
# Zhu2012 pmid=23015718
# Maksimainen2011 pmid=21130883
# Merceron2012 pmid=23012371
# Gibson2007 pmid=17455176
# Shah2008 pmid=18599462
# Czjzek2005 pmid=16212978
# Godoy2016 pmid=27685756
# Fujimoto2010 pmid=20739278
# Kitago2007 pmid=17905739
# Davies1996 pmid=15299721
# Lyu2014 pmid=24766439
# Karaveg2005 pmid=15713668
# Nerinckx2008 pmid=18619586
# Pluvinage2013 pmid=23921382
# Yuan2005 pmid=15893670
# Hoevel2003 pmid=14517232
# Espina2014 pmid=24816105
# Le_Nours2009 pmid=19089956
# Miyanaga2004 pmid=15292273
# Bianchetti2015 pmid=25752603
# Markovic-Housley2000 pmid=11080624
# Imamura2003 pmid=12618437
# Hill2013 pmid=24297913
# Maehara2014 pmid=24482228
# Miyazaki2016 pmid=27688023
# Touhara2014 pmid=24828502
# Suzuki2016 pmid=26494689
# Golan2004 pmid=14573597
# Meng2003 pmid=14517548
# Ito2011 pmid=21354427
# Hurtado-Gerrero2009 pmid=19097997
# Yaoi2007 pmid=17498741
# Thompson2015 pmid=25772148
# Barends2007 pmid=17420245
# Fujimoto2013 pmid=23486481
# Wu2015 pmid=26575439
# Pluvinage2017 pmid=28781080
# Dennis2006 pmid=16565725
# Abbott2009 pmid=19181667
# Hehemann_1_2012 pmid=23150581
# Ficko-Blean2008 pmid=18443291
# Zhu2009 pmid=20081828
# Sogabe2011 pmid=21543843
# Nam2015 pmid=26041776
# Nagae2007 pmid=17459873
# Kitamura2008 pmid=18981178
# Higgins2009 pmid=19608744
# van_Straaten2007 pmid=17502382
# van_Asselt2000 pmid=10684641
# Ndeh2017 pmid=28329766
# Labourel2019 pmid=30877196
# Luis2018 pmid=29255254
# Bule2019 pmid=31645552
# Jin2016 Jin Y, Petricevic M, John A, Raich L, Jenkins H, Portela De Souza L, Cuskin F, Gilbert HJ, Rovira C, Goddard-Borger ED, Williams SJ, and Davies GJ. ''A β-Mannanase with a Lysozyme-like Fold and a Novel Molecular Catalytic Mechanism.'' ACS Cent Sci. 2016 Nov [http://dx.doi.org/10.1021/acscentsci.6b00232 DOI:10.1021/acscentsci.6b00232]
# Yamada2017 pmid=28392148
# Ohnuma2014 pmid=24582745
# Thompson2012 pmid=22219371
# Xie2016 pmid=27777307
# Williams2014 pmid=24339341
# Hehemann_2_2012 pmid=22393053
# Huang2012 pmid=22992047
# Noach2016 pmid=27038508
# Alonso-Gil2016 pmid=28026180
# Huang2014 Huang CH, Zhu Z, Cheng YS, Chan HC, Ko TP, Chen CC, Wang I, Ho MR, Hsu ST, Zeng YF, Huang YN, Liu JR, Guo RT. ''Structure and Catalytic Mechanism of a Glycoside Hydrolase Family-127 β-L-Arabinofuranosidase (HypBA1).'' J Bioprocess Biotech. 2014 4:171 [http://dx.doi.org/10.4172/2155-9821.1000171 DOI:10.4172/2155-9821.1000171]
# Tsuda2015 pmid=26632508
# Barbirz2008 pmid=18547389
# Tanaka2019 pmid=30926603
# Armstrong2020 pmid=31871050
# Santos2020 pmid=32451508
# Kashima2021 pmid=34688653
# McGuire2020 pmid=33127644
# Shuoker2023 pmid=37005422
# Shimokawa2023 pmid=37726269
</biblio>

[[Category:Definitions and explanations]]

Syn/anti lateral protonation

2023-07-25T09:30:41Z

Wim Nerinckx: Added GH181 anti protonator

{{CuratorApproved}}
* [[Author]]: [[User:Wim Nerinckx|Wim Nerinckx]]
* [[Responsible Curator]]: [[User:Spencer Williams|Spencer Williams]]

----

== Overview ==

This page provides a table that summarizes the spatial positioning of the catalytic [[general acid]] residue in the active sites of [[glycoside hydrolase]]s, relative to the substrate. The table below updates those found in the seminal paper on this concept by Heightman and Vasella <cite>HeightmanVasella1999</cite>, and a following paper by Nerinckx ''et al.'' <cite>Nerinckx2005</cite>.

== Background ==

The ''"not from above, but from the side"'' concept of semi-lateral glycosidic oxygen [[General_acid/base|protonation]] by [[glycoside hydrolase]]s was introduced by Heightman and Vasella <cite>HeightmanVasella1999</cite>. It was originally only described for [[Anomeric centre (alpha and beta)|beta]]-equatorial [[glycoside hydrolase]]s, but appears to be equally applicable to enzymes acting on an [[Anomeric centre (alpha and beta)|alpha]]-axial glycosidic bond <cite>Nerinckx2005</cite>. When dividing [[Sub-site nomenclature|subsite -1]] into half-spaces by a plane defined by the glycosidic oxygen and C1' and H1' of the –1 glycoside, many ligand-complexed structures reveal that the [[General_acid/base|proton donor]] is positioned either in the ''syn'' half-space (near the ring-oxygen of the –1 glycoside), or in the ''anti'' half-space (on the opposite side of the ring-oxygen). Members of the same GH [[Families|family]] appear to share a common ''syn'' or ''anti'' [[General_acid/base|protonator]] arrangement and further, this specificity appears to be preserved within [[Clans|Clans]] of [[Families|families]]. This page's compilation of [[Sub-site nomenclature|subsite -1]] occupied complexes shows that about 70% of all GH [[Families|families]] are ''anti'' [[General_acid/base|protonators]].

Closer inspection of crystal structures of [[Sub-site nomenclature|–1/+1 subsite]]-spanning substrates, or substrate-analogue ligands, in complex with enzymes reveals a further intriguing corollary <cite>Nerinckx2005 Wu2012</cite>. In substrate-bound complexes with ''anti'' [[General_acid/base|protonating]] GH enzymes, the scissile [[Anomeric centre (alpha and beta)|anomeric bond]] (often studied using the thio-analogue) shows a dihedral angle φ (O5'-C1'-[O,S]x-Cx) that is in the lowest-energy synclinal (gauche) conformation. The rationale for this is that a minus synclinal dihedral angle φ for an equatorial glycosidic bond, or plus synclinal for an axial glycosidic bond <cite>Perez1978</cite>, allows for hyperconjugative overlap of the C1'-O5' antibonding orbital with an antiperiplanar-oriented lone pair orbital lobe of the glycosidic oxygen, thereby creating partial double bond character and stabilization of the glycosidic bond by 4–5 kcal/mol; this ground-state stabilizing phenomenon is known as the ‘exo-anomeric effect’ <cite>Cramer1997 Johnson2009 Alonso2016</cite>. ''Anti'' [[General_acid/base|protonation]] occurs on the glycosidic oxygen’s antiperiplanar lone pair, thereby removing the stabilizing exo-anomeric effect. This suggests that ''anti'' [[General_acid/base|protonation]] is an enzymic approach for lowering the activation barrier leading to the [[Transition state|transition state]] (Figure 1 centre).

''Syn'' [[General_acid/base|protonating]] [[glycoside hydrolase]]s apparently make use of a different approach <cite>Nerinckx2005 Wu2012</cite>. In many [[Sub-site nomenclature|–1/+1 subsite]]-spanning ligand complexes, the dihedral angle φ of the scissile anomeric bond has been rotated away from its lowest-energy synclinal position: clockwise to minus-anticlinal or antiperiplanar for beta-equatorial; counterclockwise to plus-anticlinal or antiperiplanar for alpha-axial [[Anomeric centre (alpha and beta)|anomeric bonds]]. This removes the hyperconjugative overlap and thus also the stabilizing exo-anomeric effect. And because of this rotation, a lone pair of the glycosidic oxygen is directed into the ''syn'' half-space, allowing it to be protonated by the ''syn''-positioned [[General_acid/base|proton donor]] (Figure 1 right).

[[File:Syn_anti.jpg|800px|thumb|center|Figure 1. Newman projections, with the glycosidic oxygen as proximal atom and the anomeric carbon as distal atom, showing ''anti'' (centre) versus ''syn'' (right) semi-lateral [[General_acid/base|protonation]] in beta-equatorial (top) and alpha-axial (bottom) [[glycoside hydrolase]]s. The indicated φ is the dihedral angle for O5'-C1'-O4-C4.]]

== Table of ''syn/anti'' protonation examples ==

This table contains only one example per GH [[Families|family]] of a ligand-complexed protein structure where the ''syn'' or ''anti'' positioning of the [[General_acid/base|proton donor]] can be clearly observed; other examples may be available on a [[Families|family-by-family]] basis. The reader is thus advised to consult the [http://www.cazy.org/fam/acc_GH.html#table CAZy database] for a current, comprehensive list of CAZyme structures. Where available, the selected examples are Michaelis-type complexes with the ligand spanning the [[Sub-site nomenclature|-1/+1 subsites]], since these have an intact glycosidic or thioglycosidic bond, or are ''N''-analogs of the substrate (''e.g.'' acarbose). In some examples, the [[General_acid/base|proton donor]] has been mutated (''e.g.'', to the corresponding amide or to an alanine), and in those cases one may wish to look at a superposition of the given PDB example with the structure of the native enzyme. If a Michaelis-type complex is not yet available, the second and third example choices, respectively, are trapped glycosyl-enzyme [[intermediate]]s and product complexes where [[Sub-site nomenclature|subsite -1]] is occupied.

''Please also be aware that this is a large table with many data. Please contact the page Author or Responsible Curator with corrections.''

=== Table ===
This table can be re-sorted by clicking on the icons in the header (''javascript must be turned on in your browser''). To reset the page to be sorted by GH family, click the ''View'' tab at the very top of the page.

{| {{Prettytable}} class="sortable"
|- valign="top"
! '''Family'''
! '''Clan'''
! '''Structure fold '''
! '''Anomeric specificity'''
! '''Mechanism'''
! '''''Syn/anti'' protonator'''
! '''Example PDB ID'''
! '''Enzyme'''
! '''Organism'''
! '''Ligand'''
! '''General acid'''
! '''Nucleophile or General base'''
! '''Reference'''
|-
| [[GH1]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2cer 2cer]
| β-glycosidase S
| ''Sulfolobus solfataricus'' P2
| phenethyl glucoimidazole
| '''Glu206'''
| Glu387
| <cite>Gloster2006</cite>
|-
| [[GH2]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vzu 2vzu]
| exo-β-glucosaminidase
| ''Amicolatopsis orientalis''
| PNP-β-{{Smallcaps|d}}-glucosamine
| '''Glu469'''
| Glu541
| <cite>van_Bueren2009</cite>
|-
| [[GH3]]
| none
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1iex 1iex]
| exo-1,3-1,4-glucanase
| ''Hordeum vulgare''
| thiocellobiose
| '''Glu491'''
| Asp285
| <cite>Hrmova2001</cite>
|-
| [[GH4]]
| none
| Rossmann + α6/β3 + β3/α4
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1u8x 1u8x]
| 6-P-α-glucosidase
| ''Bacillus subtilis''
| alpha-{{Smallcaps|d}}-glucose-6-phosphate
| '''Asp172'''
| not applicable
| <cite>Rajan2004</cite>
|-
| [[GH5]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1h2j 1h2j]
| endo-β-1,4-glucanase
| ''Bacillus agaradhaerens''
| 2',4'-DNP-2-F-cellobioside
| '''Glu129'''
| Glu228
| <cite>Varrot2003</cite>
|-
| [[GH6]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1qjw 1qjw]
| cellobiohydrolase 2
| ''Hypocrea jecorina''
| (Glc)2-S-(Glc)2
| '''Asp221'''
| debated
| <cite>Zhou1999</cite>
|-
| [[GH7]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1ovw 1ovw]
| endo-1,4-glucanase
| ''Fusarium oxysporum''
| thio-(Glc)5
| '''Glu202'''
| Glu197
| <cite>Sulzenbacher1999</cite>
|-
| [[GH8]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1kwf 1kwf]
| endo-1,4-glucanase
| ''Clostridium thermocellum''
| cellopentaose
| '''Glu95'''
| Asp278
| <cite>Guerin2002</cite>
|-
| [[GH9]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1rq5 1rq5]
| cellobiohydrolase
| ''Clostridium thermocellum''
| cellotetraose
| '''Glu795'''
| Asp383
| <cite>Schubot2004</cite>
|-
| [[GH10]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2d24 2d24]
| β-1,4-xylanase
| ''Streptomyces olivaceoviridis'' E-86
| xylopentaose
| '''Glu128'''
| Glu236
| <cite>Suzuki2009</cite>
|-
| [[GH11]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}4hk8 4hk8]
| endo-β-1,4-xylanase
| ''Hypocrea jecorina''
| xylohexaose
| '''Glu177'''
| Glu86
| <cite>Wan2014</cite>
|-
| [[GH12]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1w2u 1w2u]
| endoglucanase
| ''Humicola grisea''
| thiocellotetraose
| '''Glu205'''
| Glu120
| <cite>Sandgren2004</cite>
|-
| [[GH13]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1cxk 1cxk]
| β-cyclodextrin glucanotransferase
| ''Bacillus circulans''
| maltononaose
| '''Glu257'''
| Asp229
| <cite>Uitdehaag1999</cite>
|-
| [[GH14]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1itc 1itc]
| β-amylase
| ''Bacillus cereus''
| maltopentaose
| '''Glu172'''
| Glu367
| <cite>Miyake2003</cite>
|-
| [[GH15]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1dog 1dog]
| glucoamylase
| ''Aspergillus awamori''
| 1-deoxynojirimycin
| '''Glu179'''
| Glu400
| <cite>Harris1993</cite>
|-
| [[GH16]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1urx 1urx]
| β-agarase A
| ''Zobellia galactanivorans''
| oligoagarose
| '''Glu152'''
| Glu147
| <cite>Allouch2004</cite>
|-
| [[GH17]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzj 4gzj]
| endo-β-1,3-glucanase
| ''Solanum tuberosum''
| laminaratriose + laminarabiose
| '''Glu118'''
| Glu259
| <cite>Wojtkowiak2013</cite>
|-
| [[GH18]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1ffr 1ffr]
| chitinase A
| ''Serratia marcescens''
| (NAG)6
| '''Glu315'''
| internal
| <cite>Papanikolau2001</cite>
|-
| [[GH19]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}3wh1 3wh1]
| chitinase
| ''Bryum coronatum''
| (GlcNAc)4
| '''Glu61'''
| Glu70
| <cite>Ohnuma2014</cite>
|-
| [[GH20]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1c7s 1c7s]
| chitobiase
| ''Serratia marcescens''
| chitobiose
| '''Glu540'''
| internal
| <cite>Prag2000</cite>
|-
| [[GH22]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1h6m 1h6m]
| lysozyme C
| ''Gallus gallus''
| Chit-2-F-chitosyl
| '''Glu35'''
| Asp52
| <cite>Vocadlo2001</cite>
|-
| [[GH23]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1lsp 1lsp]
| lysozyme G
| ''Cygnus atratus''
| Bulgecin A
| '''Glu73'''
| internal
| <cite>Karlsen1996</cite>
|-
| [[GH24]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}148l 148l]
| lysozyme E
| Bacteriophage T4
| chitobiosyl
| '''Glu11'''
| Glu26
| <cite>Baldwin1993</cite>
|-
| [[GH26]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vx6 2vx6]
| exo-β-mannanase
| ''Cellvibrio japonicus'' Ueda107
| Gal1Man4
| '''Glu221'''
| Glu338
| <cite>Cartmell2008</cite>
|-
| [[GH27]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}} / beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3lrm 3lrm]
| α-galactosidase
| ''Saccharomyces cerevisiae''
| raffinose
| '''Asp209'''
| Asp141
| <cite>Fernandez-Leiro2010</cite>
|-
| [[GH28]]
| N
| β-helix
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}2uvf 2uvf]
| exo-polygalacturonosidase
| ''Yersinia enterocolitica'' ATCC9610D
| digalacturonic acid
| '''Asp402'''
| Asp381 Asp403
| <cite>Abbott2007</cite>
|-
| [[GH29]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| '''''syn'''''
| [{{PDBlink}}3uet 3uet]
| α-1,3/4-fucosidase
| ''Bifidobacterium longum'' subsp. infantis
| lacto-''N''-fucopentaose II
| '''Glu217'''
| Asp172
| <cite>Sakurama2012</cite>
|-
| [[GH30]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2y24 2y24]
| glucurono-xylanase
| ''Dickea chrysanthemi'' D1
| glucuronoxylan tetrasaccharide
| '''Glu163'''
| Glu253
| <cite>Urbanikova2011</cite>
|-
| [[GH31]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2qmj 2qmj]
| maltase-glucoamylase
| ''Homo sapiens''
| acarbose
| '''Asp542'''
| Asp443
| <cite>Sim2008</cite>
|-
| [[GH32]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2add 2add]
| fructan β-(2,1)-fructosidase
| ''Cichorium intybus''
| sucrose
| '''Glu201'''
| Asp22
| <cite>Verhaest2007</cite>
|-
| [[GH33]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1s0i 1s0i]
| transsialidase
| ''Trypanosoma cruzi''
| sialyllactose
| '''Asp59'''
| Tyr342
| <cite>Amaya2004</cite>
|-
| [[GH34]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzw 4gzw]
| N2 neuraminidase
| ''Influenza'' A Tanzania/205/2010 H3N2
| α-{{Smallcaps|d}}-Neup5Ac-(2,3)-β-{{Smallcaps|d}}-Galp-(1,4)-β-{{Smallcaps|d}}-GlcpNAc
| '''Asp151'''
| Tyr406
| <cite>Zhu2012</cite>
|-
| [[GH35]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3ogv 3ogv]
| β-galactosidase
| ''Hypocrea jecorina''
| 2-phenylethyl 1-thio-β-{{Smallcaps|d}}-galactopyranoside
| '''Glu200'''
| Glu298
| <cite>Maksimainen2011</cite>
|-
| [[GH36]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4fnu 4fnu]
| β-galactosidase
| ''Geobacillus stearothermophilus''
| stachyose
| '''Asp584'''
| Asp478
| <cite>Merceron2012</cite>
|-
| [[GH37]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2jf4 2jf4]
| trehalase
| ''Escherichia coli''
| validoxylamine
| '''Asp312'''
| Glu496
| <cite>Gibson2007</cite>
|-
| [[GH38]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3czn 3czn]
| Golgi α-mannosidase II
| ''Drosophila melanogaster''
| GlcNAcMan(5)GlcNAc(2)
| '''Asp341'''
| Asp204
| <cite>Shah2008</cite>
|-
| [[GH39]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2bfg 2bfg]
| β-xylosidase
| ''Geobacillus stearothermophilus''
| 2,5-dinitrophenyl-β-{{Smallcaps|d}}-xyloside
| '''Glu160'''
| Glu278
| <cite>Czjzek2005</cite>
|-
| [[GH42]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ucf 4ucf]
| β-galactosidase
| ''Bifidobacterium bifidum''
| {{Smallcaps|d}}-galactose
| '''Glu161'''
| Glu320
| <cite>Godoy2016</cite>
|-
| [[GH43]]
| F
| 5-fold β-propeller
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3akh 3akh]
| exo-1,5-α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces avermitilis''
| α-1,5-arabinofuranotriose
| '''Glu196'''
| Asp220
| <cite>Fujimoto2010</cite>
|-
| [[GH44]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2eqd 2eqd]
| endoglucanase
| ''Clostridium thermocellum''
| cellooctaose
| '''Glu186'''
| Glu359
| <cite>Kitago2007</cite>
|-
| [[GH45]]
| none
| 6-stranded β-barrel
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4eng 4eng]
| endo-1,4-glucanase
| ''Humicola insolens''
| cellohexaose
| '''Asp121'''
| Asp10
| <cite>Davies1996</cite>
|-
| [[GH46]]
| I
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4olt 4olt]
| chitosanase
| ''Microbacterium sp.'' OU01
| hexa-glucosamine
| '''Glu25'''
| Asp43
| <cite>Lyu2014</cite>
|-
| [[GH47]]
| none
| (α/α)7
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1x9d 1x9d]
| α-mannosidase I
| ''Homo sapiens''
| Me-2-S-(α-Man)-2-thio-α-Man
| '''Asp463'''
| Glu599
| <cite>Karaveg2005</cite>, <cite>Nerinckx2008</cite>
|-
| [[GH48]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH8''
|
|
|
|
|
|
|-
| [[GH49]]
| N
| β-helix
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH28''
|
|
|
|
|
|
|-
| [[GH50]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4bq5 4bq5]
| exo-β-agarase
| ''Saccharophagus degradans''
| neoagarotetraose
| '''Glu535'''
| Glu695
| <cite>Pluvinage2013</cite>
|-
| [[GH51]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1qw9 1qw9]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Geobacillus stearothermophilus''
| PNP-{{Smallcaps|l}}-arabinofuranoside
| '''Glu175'''
| Glu294
| <cite>Hoevel2003</cite>
|-
| [[GH52]]
| O
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4c1p 4c1p]
| β-xylosidase
| ''Geobacillus thermoglucosidasius''
| xylobiose
| '''Asp517'''
| Glu537
| <cite>Espina2014</cite>
|-
| [[GH53]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2ccr 2ccr]
| β-1,4-galactanase
| ''Bacillus licheniformis''
| galactotriose
| '''Glu165'''
| Glu263
| <cite>Le_Nours2009</cite>
|-
| [[GH54]]
| none
| β-sandwich
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1wd4 1wd4]
| α-{{Smallcaps|l}}-arabinofuranosidase B
| ''Aspergillus kawachii''
| {{Smallcaps|l}}-arabinofuranose
| '''Asp297'''
| Glu221
| <cite>Miyanaga2004</cite>
|-
| [[GH55]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4tz5 4tz5]
| exo-β-1,3-glucanase
| ''Streptomyces sp.'' SirexAA-E
| laminarihexaose
| '''Glu502'''
| unknown
| <cite>Bianchetti2015</cite>
|-
| [[GH56]]
| none
| (β/α)7
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1fcv 1fcv]
| hyaluronidase
| ''Apis mellifera''
| (hyaluron.)4
| '''Glu113'''
| internal
| <cite>Markovic-Housley2000</cite>
|-
| [[GH57]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1k1y 1k1y]
| glucanotransferase
| ''Thermococcus litoralis''
| acarbose
| '''Asp214'''
| Glu123
| <cite>Imamura2003</cite>
|-
| [[GH59]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ccc 4ccc]
| β-galactocerebrosidase
| ''Mus musculus''
| PNP-β-{{Smallcaps|d}}-galactoside
| '''Glu182'''
| Glu258
| <cite>Hill2013</cite>
|-
| [[GH62]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3wn0 3wn0]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces coelicolor''
| β-{{Smallcaps|l}}-Arabinofuranose
| '''Glu361'''
| Asp202
| <cite>Maehara2014</cite>
|-
| [[GH63]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5ca3 5ca3]
| α-glucosidase
| ''Escherichia coli''
| glucose and lactose
| '''Asp501'''
| Glu727
| <cite>Miyazaki2016</cite>
|-
| [[GH65]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}4ktr 4ktr]
| 2-O-α-glucosylglycerol phosphorylase
| ''Bacillus selenitireducens''
| isofagomine
| '''Glu475'''
| phosphate
| <cite>Touhara2014</cite>
|-
| [[GH66]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5axh 5axh]
| dextranase
| ''Thermoanaerobacter pseudethanolicus''
| isomaltohexaose
| '''Glu374'''
| Asp312
| <cite>Suzuki2016</cite>
|-
| [[GH67]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1l8n 1l8n]
| α-glucuronidase
| ''Geobacillus stearothermophilus''
| 4-O-methyl-{{Smallcaps|d}}-glucuronic acid and xylotriose
| '''Glu286'''
| Asp364 Glu392
| <cite>Golan2004</cite>
|-
| [[GH68]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1pt2 1pt2]
| levansucrase
| ''Bacillus subtilis''
| sucrose
| '''Glu342'''
| Asp86
| <cite>Meng2003</cite>
|-
| [[GH70]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3aic 3aic]
| glucansucrase
| ''Streptococcus mutans''
| α-acarbose
| '''Glu515'''
| Asp477
| <cite>Ito2011</cite>
|-
| [[GH72]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w62 2w62]
| β-1,3-glucanotransferase
| ''Saccharomyces cerevisiae'' S288C
| laminaripentaose
| '''Glu176'''
| Glu275
| <cite>Hurtado-Gerrero2009</cite>
|-
| [[GH74]]
| none
| 7-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}2ebs 2ebs]
| cellobiohydrolase (OXG-RCBH)
| ''Geotrichum sp.'' m128
| xyloglucan heptasaccharide
| '''Asp465'''
| Asp35
| <cite>Yaoi2007</cite>
|-
| [[GH76]]
| none
| (α/α)6
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5agd 5agd]
| endo-α-1,6-mannanase
| ''Bacillus circulans''
| α-1,6-mannopentaose
| '''Asp125'''
| Asp124
| <cite>Thompson2015</cite>
|-
| [[GH77]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2oww 2oww]
| 4-α-glucanotransferase
| ''Thermus thermofilus''
| acarbose + 4-deoxy-α-{{Smallcaps|d}}-glucose
| '''Glu340'''
| Asp293
| <cite>Barends2007</cite>
|-
| [[GH78]]
| H
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3w5n 3w5n]
| α-{{Smallcaps|l}}-rhamnosidase
| ''Streptomyces avermitilis''
| {{Smallcaps|l}}-rhamnose
| '''Glu636'''
| Glu895
| <cite>Fujimoto2013</cite>
|-
| [[GH79]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5e9c 5e9c]
| heparanase
| ''Homo sapiens''
| heparin tetrasaccharide
| '''Glu225'''
| Glu343
| <cite>Wu2015</cite>
|-
| [[GH80]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH24''
|
|
|
|
|
|
|-
| [[GH81]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5t4g 5t4g]
| endo-β-1,3-glucanase
| ''Bacillus halodurans'' C-125
| laminarin
| '''Asp466'''
| Glu542
| <cite>Pluvinage2017</cite>
|-
| [[GH83]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1z4x 1z4x]
| hemagglutinin-neuraminidase
| Simian virus 5
| α-2,3-sialyllactose
| '''Glu247''' relay
| Tyr523
| <cite>Yuan2005</cite>
|-
| [[GH84]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2chn 2chn]
| β-''N''-acetyl-glucosaminidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| NAG-thiazoline
| '''Glu242'''
| internal
| <cite>Dennis2006</cite>
|-
| [[GH85]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w92 2w92]
| endo-β-''N''-acetyl-glucosaminidase D
| ''Streptococcus pneumoniae'' TIGR4
| NAG-thiazoline
| '''Glu337'''
| internal
| <cite>Abbott2009</cite>
|-
| [[GH86]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4aw7 4aw7]
| β-porphyranase
| ''Bacteroides plebeius''
| porphyran fragment
| '''Glu152'''
| Glu279
| <cite>Hehemann_1_2012</cite>
|-
| [[GH89]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vcb 2vcb]
| α-''N''-acetyl-glucosaminidase
| ''Clostridium perfringens''
| PUGNAc
| '''Glu483'''
| Glu601
| <cite>Ficko-Blean2008</cite>
|-
| [[GH92]]
| none
| (α/α)6 and β-sandwich
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ww1 2ww1]
| α-1,2-mannosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| thiomannobioside
| '''Glu533'''
| Asp644 Asp642
| <cite>Zhu2009</cite>
|-
| [[GH93]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3a72 3a72]
| exo-arabinanase
| ''Penicillium chrysogenum''
| arabinobiose
| '''Glu246'''
| Glu174
| <cite>Sogabe2011</cite>
|-
| [[GH94]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4zli 4zli]
| cellobionic acid phosphorylase
| ''Saccharophagus degradans''
| 3-O-β-{{Smallcaps|d}}-glucopyranosyl-α-{{Smallcaps|d}}-glucopyranuronic acid
| '''Asp472'''
| phosphate
| <cite>Nam2015</cite>
|-
| [[GH95]]
| none
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ead 2ead]
| α-1,2-{{Smallcaps|l}}-fucosidase
| ''Bifidobacterium bifidum''
| Fuc-α-1,2-Gal
| '''Glu566'''
| Asn423 Asp766
| <cite>Nagae2007</cite>
|-
| [[GH97]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining + inverting
| '''''anti'''''
| [{{PDBlink}}2zq0 2zq0]
| α-glucosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| acarbose
| '''Glu532'''
| Glu508
| <cite>Kitamura2008</cite>
|-
| [[GH98]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2wmg 2wmg]
| endo-β-1,4-galactosidase
| ''Streptococcus pneumoniae''
| A-LewisY pentasaccharide
| '''Glu158'''
| Asp251 Glu301
| <cite>Higgins2009</cite>
|-
| [[GH99]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ad4 4ad4]
| endo-α-mannosidase
| ''Bacteroides xylanisolvens''
| glucose-1,3-isofagomine and α-1,2- mannobiose
| '''Glu336'''
| debated
| <cite>Thompson2012</cite>
|-
| [[GH100]]
| none
| (α/α)6 core
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5gop 5gop]
| invertase
| ''Anabaena (Nostoc) sp.'' pcc7120
| sucrose
| '''Asp188'''
| Glu414
| <cite>Xie2016</cite>
|-
| [[GH102]]
| none
| double-ψ β-barrel
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}2pi8 2pi8]
| lytic transglycosylase A
| ''Escherichia coli''
| chitohexaose
| '''Asp308'''
| none
| <cite>van_Straaten2007</cite>
|-
| [[GH103]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1d0k 1d0k]
| lytic transglycosylase SLT35
| ''Escherichia coli''
| murodipeptides
| '''Glu162'''
| internal
| <cite>van_Asselt2000</cite>
|-
| [[GH106]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5mwk 5mwk]
| α-{{Smallcaps|l}}-rhamnosidase BT_0986
| ''Bacteroides thetaiotaomicron''
| pectin heptasaccharide
| '''Glu461'''
| Glu593 or Glu561
| <cite>Ndeh2017</cite>
|-
| [[GH107]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| ''predicted syn by clan''
| ''see at GH29''
|
|
|
|
|
|
|-
| [[GH110]]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}7jwf 7jwf]
| α-1,3-galactosidase
| ''Pseudoalteromonas distincta''
| Gal-α1,3-Gal
| '''Asp344'''
| Asp321 Asp345
| <cite>McGuire2020</cite>
|-
| [[GH113]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4cd8 4cd8]
| β-mannanase
| ''Alicyclobacillus acidocaldarius''
| mannobioimidazole
| '''Glu151'''
| Glu231
| <cite>Williams2014</cite>
|-
| [[GH116]]
| O
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at GH52''
|
|
|
|
|
|
|-
| [[GH117]]
| none
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}4ak7 4ak7]
| α-1,3-3,6-anhydro-{{Smallcaps|l}}-galactosidase
| ''Bacteroides plebeius''
| neoagarobiose
| '''His302''' (relay from Asp320)
| Asp90
| <cite>Hehemann_2_2012</cite>
|-
| [[GH120]]
| none
| parallel β-helix and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3vsv 3vsv]
| β-xylosidase XylC
| ''Thermoanaerobacterium saccharolyticum'' JW/SL-YS485
| {{Smallcaps|d}}-xylose
| '''Glu405'''
| Asp382
| <cite>Huang2012</cite>
|-
| [[GH123]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5fr0 5fr0]
| exo-β-N-acetyl-galactosaminidase
| ''Clostridium perfringens''
| ''N''-difluoroacetyl-{{Smallcaps|d}}-galactosamine
| '''Glu345'''
| internal
| <cite>Noach2016</cite>
|-
| [[GH125]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5m7y 5m7y]
| exo-α-1,6-mannosidase
| ''Clostridium perfringens''
| 1,6-α-mannotriose
| '''Asp220'''
| Glu393
| <cite>Alonso-Gil2016</cite>
|-
| [[GH127]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3wrg 3wrg]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bifidobacterium longum''
| {{Smallcaps|l}}-arabinose
| '''Glu322'''
| Cys417
| <cite>Huang2014</cite>
|-
| [[GH128]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}6ufl 6ufl]
| β-1,3-glucanase
| ''Amycolatopsis mediterranei''
| laminarihexaose
| '''Glu102'''
| Glu199
| <cite>Santos2020</cite>
|-
| [[GH130]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5b0s 5b0s]
| β-1,2-mannobiose phosphorylase
| ''Listeria innocua''
| β-1,2-mannotriose
| '''Asp141''' relay
| phosphate
| <cite>Tsuda2015</cite>
|-
| [[GH134]]
| none
| β + α
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5jug 5jug]
| β-mannanase
| ''Streptomyces sp.''
| mannopentaose
| '''Glu45'''
| Asp57
| <cite>Jin2016</cite>
|-
| [[GH136]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}5gqf 5gqf]
| lacto-N-biosidase
| ''Bifidobacterium longum''
| lacto-N-biose
| '''Asp411'''
| Asp418
| <cite>Yamada2017</cite>
|-
| [[GH137]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|l}}
| unknown
| '''''anti'''''
| [{{PDBlink}}5mui 5mui]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0996
| ''Bacteroides thetaiotaomicron''
| pectin oligosaccharide
| '''Glu240'''
| Glu159
| <cite>Ndeh2017</cite>
|-
| [[GH138]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}6hzg 6hzg]
| α-1,2-{{Smallcaps|d}}-galacturonidase
| ''Bacteroides paurosaccharolyticus''
| alpha-{{Smallcaps|d}}-galactopyranuronic
| '''Glu294'''
| Glu361
| <cite>Labourel2019</cite>
|-
| [[GH146]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5opj 5opj]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0349
| ''Bacteroides thetaiotaomicron''
| {{Smallcaps|l}}-arabinose
| '''Glu320'''
| Cys416
| <cite>Luis2018</cite>
|-
| [[GH147]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH148]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH149]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH156]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}6s0e 6s0e]
| exo-α-sialidase
| uncultured bacterium pG7
| N-acetyl-2,3-dehydro-2-deoxyneuraminic acid
| '''His134''' (relay from Asp132)
| Asp14
| <cite>Bule2019</cite>
|-
| [[GH157]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH158]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH161]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH162]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}6imw 6imw]
| endo-β-1,2-glucanase
| ''Talaromyces funiculosus''
| beta-1,2-glucan
| '''Glu262''' via C3-OH of glc at subs. +2
| Asp446
| <cite>Tanaka2019</cite>
|-
| [[GH164]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}6t75 6t75]
| β-mannosidase
| ''Bacteroides salyersiae''
| 2-deoxy-2-F-mannosyl
| '''Glu160'''
| Glu297
| <cite>Armstrong2020</cite>
|-
| [[GH172]]
| none
| β-jelly roll
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}7v1w 7v1w]
| difructose-anhydride synthase
| ''Bifidobacterium dentum''
| beta-{{Smallcaps|d}}-arabinofuranose
| '''Glu270'''
| Glu291
| <cite>Kashima2021</cite>

|-
| [[GH181]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}8axi 8axi]
| exo-α-sialidase
| ''Akkermansia muciniphila''
| 2-deoxy-2,3-dehydro-''N''-acetyl-neuraminic acid + T-antigen disaccharide
| '''Asp345'''
| Glu218
| <cite>Shuoker2023</cite>

|-

| [http://www.cazy.org/GH0.html n.c.*]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2vjj 2vjj]
| endo-α-N-acetylglucosaminidase
| Bacteriophage HK620
| O18A1 O-antigen hexasaccharide
| '''Asp339'''
| Glu372
| <cite>Barbirz2008</cite>
|}
<nowiki>*</nowiki> n.c.: Found among the collection of [http://www.cazy.org/GH0.html non-classified GH sequences in the CAZy Database].

== References ==

<biblio>
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# Wu2012 pmid=23137336
# Perez1978 Pérez S and Marchessault RH. ''The exo-anomeric effect: experimental evidence from crystal structures.'' Carbohydr res. 1978 65:114-120. [http://dx.doi.org/10.1016/S0008-6215(00)84218-4 DOI:10.1016/S0008-6215(00)84218-4]
# Cramer1997 Cramer CJ, Truhlar DG, and French AD. ''Exo-anomeric effects on energies and geometries of different conformations of glucose and related systems in the gas phase and aqueous solution.'' Carbohydr res. 1997 298:1-14. [http://dx.doi.org/10.1016/S0008-6215(96)00297-2 DOI:10.1016/S0008-6215(96)00297-2]
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# Maehara2014 pmid=24482228
# Miyazaki2016 pmid=27688023
# Touhara2014 pmid=24828502
# Suzuki2016 pmid=26494689
# Golan2004 pmid=14573597
# Meng2003 pmid=14517548
# Ito2011 pmid=21354427
# Hurtado-Gerrero2009 pmid=19097997
# Yaoi2007 pmid=17498741
# Thompson2015 pmid=25772148
# Barends2007 pmid=17420245
# Fujimoto2013 pmid=23486481
# Wu2015 pmid=26575439
# Pluvinage2017 pmid=28781080
# Dennis2006 pmid=16565725
# Abbott2009 pmid=19181667
# Hehemann_1_2012 pmid=23150581
# Ficko-Blean2008 pmid=18443291
# Zhu2009 pmid=20081828
# Sogabe2011 pmid=21543843
# Nam2015 pmid=26041776
# Nagae2007 pmid=17459873
# Kitamura2008 pmid=18981178
# Higgins2009 pmid=19608744
# van_Straaten2007 pmid=17502382
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# Ndeh2017 pmid=28329766
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# Luis2018 pmid=29255254
# Bule2019 pmid=31645552
# Jin2016 Jin Y, Petricevic M, John A, Raich L, Jenkins H, Portela De Souza L, Cuskin F, Gilbert HJ, Rovira C, Goddard-Borger ED, Williams SJ, and Davies GJ. ''A β-Mannanase with a Lysozyme-like Fold and a Novel Molecular Catalytic Mechanism.'' ACS Cent Sci. 2016 Nov [http://dx.doi.org/10.1021/acscentsci.6b00232 DOI:10.1021/acscentsci.6b00232]
# Yamada2017 pmid=28392148
# Ohnuma2014 pmid=24582745
# Thompson2012 pmid=22219371
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# Shuoker2023 pmid=37005422

</biblio>
[[Category:Definitions and explanations]]

Syn/anti lateral protonation

2021-11-23T15:23:45Z

Wim Nerinckx: GH110 anti-protonating

{{CuratorApproved}}
* [[Author]]: ^^^Wim Nerinckx^^^
* [[Responsible Curator]]: ^^^Spencer Williams^^^

----

== Overview ==

This page provides a table that summarizes the spatial positioning of the catalytic [[general acid]] residue in the active sites of [[glycoside hydrolase]]s, relative to the substrate. The table below updates those found in the seminal paper on this concept by Heightman and Vasella <cite>HeightmanVasella1999</cite>, and a following paper by Nerinckx ''et al.'' <cite>Nerinckx2005</cite>.

== Background ==

The ''"not from above, but from the side"'' concept of semi-lateral glycosidic oxygen [[General_acid/base|protonation]] by [[glycoside hydrolase]]s was introduced by Heightman and Vasella <cite>HeightmanVasella1999</cite>. It was originally only described for [[Anomeric centre (alpha and beta)|beta]]-equatorial [[glycoside hydrolase]]s, but appears to be equally applicable to enzymes acting on an [[Anomeric centre (alpha and beta)|alpha]]-axial glycosidic bond <cite>Nerinckx2005</cite>. When dividing [[Sub-site nomenclature|subsite -1]] into half-spaces by a plane defined by the glycosidic oxygen and C1' and H1' of the –1 glycoside, many ligand-complexed structures reveal that the [[General_acid/base|proton donor]] is positioned either in the ''syn'' half-space (near the ring-oxygen of the –1 glycoside), or in the ''anti'' half-space (on the opposite side of the ring-oxygen). Members of the same GH [[Families|family]] appear to share a common ''syn'' or ''anti'' [[General_acid/base|protonator]] arrangement and further, this specificity appears to be preserved within [[Clans|Clans]] of [[Families|families]]. This page's compilation of [[Sub-site nomenclature|subsite -1]] occupied complexes shows that about 70% of all GH [[Families|families]] are ''anti'' [[General_acid/base|protonators]].

Closer inspection of crystal structures of [[Sub-site nomenclature|–1/+1 subsite]]-spanning substrates, or substrate-analogue ligands, in complex with enzymes reveals a further intriguing corollary <cite>Nerinckx2005 Wu2012</cite>. In substrate-bound complexes with ''anti'' [[General_acid/base|protonating]] GH enzymes, the scissile [[Anomeric centre (alpha and beta)|anomeric bond]] (often studied using the thio-analogue) shows a dihedral angle φ (O5'-C1'-[O,S]x-Cx) that is in the lowest-energy synclinal (gauche) conformation. The rationale for this is that a minus synclinal dihedral angle φ for an equatorial glycosidic bond, or plus synclinal for an axial glycosidic bond <cite>Perez1978</cite>, allows for hyperconjugative overlap of the C1'-O5' antibonding orbital with an antiperiplanar-oriented lone pair orbital lobe of the glycosidic oxygen, thereby creating partial double bond character and stabilization of the glycosidic bond by 4–5 kcal/mol; this ground-state stabilizing phenomenon is known as the ‘exo-anomeric effect’ <cite>Cramer1997 Johnson2009 Alonso2016</cite>. ''Anti'' [[General_acid/base|protonation]] occurs on the glycosidic oxygen’s antiperiplanar lone pair, thereby removing the stabilizing exo-anomeric effect. This suggests that ''anti'' [[General_acid/base|protonation]] is an enzymic approach for lowering the activation barrier leading to the [[Transition state|transition state]] (Figure 1 centre).

''Syn'' [[General_acid/base|protonating]] [[glycoside hydrolase]]s apparently make use of a different approach <cite>Nerinckx2005 Wu2012</cite>. In many [[Sub-site nomenclature|–1/+1 subsite]]-spanning ligand complexes, the dihedral angle φ of the scissile anomeric bond has been rotated away from its lowest-energy synclinal position: clockwise to minus-anticlinal or antiperiplanar for beta-equatorial; counterclockwise to plus-anticlinal or antiperiplanar for alpha-axial [[Anomeric centre (alpha and beta)|anomeric bonds]]. This removes the hyperconjugative overlap and thus also the stabilizing exo-anomeric effect. And because of this rotation, a lone pair of the glycosidic oxygen is directed into the ''syn'' half-space, allowing it to be protonated by the ''syn''-positioned [[General_acid/base|proton donor]] (Figure 1 right).

[[File:Syn_anti.jpg|800px|thumb|center|Figure 1. Newman projections, with the glycosidic oxygen as proximal atom and the anomeric carbon as distal atom, showing ''anti'' (centre) versus ''syn'' (right) semi-lateral [[General_acid/base|protonation]] in beta-equatorial (top) and alpha-axial (bottom) [[glycoside hydrolase]]s. The indicated φ is the dihedral angle for O5'-C1'-O4-C4.]]

== Table of ''syn/anti'' protonation examples ==

This table contains only one example per GH [[Families|family]] of a ligand-complexed protein structure where the ''syn'' or ''anti'' positioning of the [[General_acid/base|proton donor]] can be clearly observed; other examples may be available on a [[Families|family-by-family]] basis. The reader is thus advised to consult the [http://www.cazy.org/fam/acc_GH.html#table CAZy database] for a current, comprehensive list of CAZyme structures. Where available, the selected examples are Michaelis-type complexes with the ligand spanning the [[Sub-site nomenclature|-1/+1 subsites]], since these have an intact glycosidic or thioglycosidic bond, or are ''N''-analogs of the substrate (''e.g.'' acarbose). In some examples, the [[General_acid/base|proton donor]] has been mutated (''e.g.'', to the corresponding amide or to an alanine), and in those cases one may wish to look at a superposition of the given PDB example with the structure of the native enzyme. If a Michaelis-type complex is not yet available, the second and third example choices, respectively, are trapped glycosyl-enzyme [[intermediate]]s and product complexes where [[Sub-site nomenclature|subsite -1]] is occupied.

''Please also be aware that this is a large table with many data. Please contact the page Author or Responsible Curator with corrections.''

=== Table ===
This table can be re-sorted by clicking on the icons in the header (''javascript must be turned on in your browser''). To reset the page to be sorted by GH family, click the ''View'' tab at the very top of the page.

{| {{Prettytable}} class="sortable"
|- valign="top"
! '''Family'''
! '''Clan'''
! '''Structure fold '''
! '''Anomeric specificity'''
! '''Mechanism'''
! '''''Syn/anti'' protonator'''
! '''Example PDB ID'''
! '''Enzyme'''
! '''Organism'''
! '''Ligand'''
! '''General acid'''
! '''Nucleophile or General base'''
! '''Reference'''
|-
| [[GH1]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2cer 2cer]
| β-glycosidase S
| ''Sulfolobus solfataricus'' P2
| phenethyl glucoimidazole
| '''Glu206'''
| Glu387
| <cite>Gloster2006</cite>
|-
| [[GH2]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vzu 2vzu]
| exo-β-glucosaminidase
| ''Amicolatopsis orientalis''
| PNP-β-{{Smallcaps|d}}-glucosamine
| '''Glu469'''
| Glu541
| <cite>van_Bueren2009</cite>
|-
| [[GH3]]
| none
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1iex 1iex]
| exo-1,3-1,4-glucanase
| ''Hordeum vulgare''
| thiocellobiose
| '''Glu491'''
| Asp285
| <cite>Hrmova2001</cite>
|-
| [[GH4]]
| none
| Rossmann + α6/β3 + β3/α4
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1u8x 1u8x]
| 6-P-α-glucosidase
| ''Bacillus subtilis''
| alpha-{{Smallcaps|d}}-glucose-6-phosphate
| '''Asp172'''
| not applicable
| <cite>Rajan2004</cite>
|-
| [[GH5]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1h2j 1h2j]
| endo-β-1,4-glucanase
| ''Bacillus agaradhaerens''
| 2',4'-DNP-2-F-cellobioside
| '''Glu129'''
| Glu228
| <cite>Varrot2003</cite>
|-
| [[GH6]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1qjw 1qjw]
| cellobiohydrolase 2
| ''Hypocrea jecorina''
| (Glc)2-S-(Glc)2
| '''Asp221'''
| debated
| <cite>Zhou1999</cite>
|-
| [[GH7]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1ovw 1ovw]
| endo-1,4-glucanase
| ''Fusarium oxysporum''
| thio-(Glc)5
| '''Glu202'''
| Glu197
| <cite>Sulzenbacher1999</cite>
|-
| [[GH8]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1kwf 1kwf]
| endo-1,4-glucanase
| ''Clostridium thermocellum''
| cellopentaose
| '''Glu95'''
| Asp278
| <cite>Guerin2002</cite>
|-
| [[GH9]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1rq5 1rq5]
| cellobiohydrolase
| ''Clostridium thermocellum''
| cellotetraose
| '''Glu795'''
| Asp383
| <cite>Schubot2004</cite>
|-
| [[GH10]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2d24 2d24]
| β-1,4-xylanase
| ''Streptomyces olivaceoviridis'' E-86
| xylopentaose
| '''Glu128'''
| Glu236
| <cite>Suzuki2009</cite>
|-
| [[GH11]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}4hk8 4hk8]
| endo-β-1,4-xylanase
| ''Hypocrea jecorina''
| xylohexaose
| '''Glu177'''
| Glu86
| <cite>Wan2014</cite>
|-
| [[GH12]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1w2u 1w2u]
| endoglucanase
| ''Humicola grisea''
| thiocellotetraose
| '''Glu205'''
| Glu120
| <cite>Sandgren2004</cite>
|-
| [[GH13]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1cxk 1cxk]
| β-cyclodextrin glucanotransferase
| ''Bacillus circulans''
| maltononaose
| '''Glu257'''
| Asp229
| <cite>Uitdehaag1999</cite>
|-
| [[GH14]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1itc 1itc]
| β-amylase
| ''Bacillus cereus''
| maltopentaose
| '''Glu172'''
| Glu367
| <cite>Miyake2003</cite>
|-
| [[GH15]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1dog 1dog]
| glucoamylase
| ''Aspergillus awamori''
| 1-deoxynojirimycin
| '''Glu179'''
| Glu400
| <cite>Harris1993</cite>
|-
| [[GH16]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1urx 1urx]
| β-agarase A
| ''Zobellia galactanivorans''
| oligoagarose
| '''Glu152'''
| Glu147
| <cite>Allouch2004</cite>
|-
| [[GH17]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzj 4gzj]
| endo-β-1,3-glucanase
| ''Solanum tuberosum''
| laminaratriose + laminarabiose
| '''Glu118'''
| Glu259
| <cite>Wojtkowiak2013</cite>
|-
| [[GH18]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1ffr 1ffr]
| chitinase A
| ''Serratia marcescens''
| (NAG)6
| '''Glu315'''
| internal
| <cite>Papanikolau2001</cite>
|-
| [[GH19]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}3wh1 3wh1]
| chitinase
| ''Bryum coronatum''
| (GlcNAc)4
| '''Glu61'''
| Glu70
| <cite>Ohnuma2014</cite>
|-
| [[GH20]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1c7s 1c7s]
| chitobiase
| ''Serratia marcescens''
| chitobiose
| '''Glu540'''
| internal
| <cite>Prag2000</cite>
|-
| [[GH22]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1h6m 1h6m]
| lysozyme C
| ''Gallus gallus''
| Chit-2-F-chitosyl
| '''Glu35'''
| Asp52
| <cite>Vocadlo2001</cite>
|-
| [[GH23]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1lsp 1lsp]
| lysozyme G
| ''Cygnus atratus''
| Bulgecin A
| '''Glu73'''
| internal
| <cite>Karlsen1996</cite>
|-
| [[GH24]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}148l 148l]
| lysozyme E
| Bacteriophage T4
| chitobiosyl
| '''Glu11'''
| Glu26
| <cite>Baldwin1993</cite>
|-
| [[GH26]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vx6 2vx6]
| exo-β-mannanase
| ''Cellvibrio japonicus'' Ueda107
| Gal1Man4
| '''Glu221'''
| Glu338
| <cite>Cartmell2008</cite>
|-
| [[GH27]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}} / beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3lrm 3lrm]
| α-galactosidase
| ''Saccharomyces cerevisiae''
| raffinose
| '''Asp209'''
| Asp141
| <cite>Fernandez-Leiro2010</cite>
|-
| [[GH28]]
| N
| β-helix
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}2uvf 2uvf]
| exo-polygalacturonosidase
| ''Yersinia enterocolitica'' ATCC9610D
| digalacturonic acid
| '''Asp402'''
| Asp381 Asp403
| <cite>Abbott2007</cite>
|-
| [[GH29]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| '''''syn'''''
| [{{PDBlink}}3uet 3uet]
| α-1,3/4-fucosidase
| ''Bifidobacterium longum'' subsp. infantis
| lacto-''N''-fucopentaose II
| '''Glu217'''
| Asp172
| <cite>Sakurama2012</cite>
|-
| [[GH30]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2y24 2y24]
| glucurono-xylanase
| ''Dickea chrysanthemi'' D1
| glucuronoxylan tetrasaccharide
| '''Glu163'''
| Glu253
| <cite>Urbanikova2011</cite>
|-
| [[GH31]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2qmj 2qmj]
| maltase-glucoamylase
| ''Homo sapiens''
| acarbose
| '''Asp542'''
| Asp443
| <cite>Sim2008</cite>
|-
| [[GH32]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2add 2add]
| fructan β-(2,1)-fructosidase
| ''Cichorium intybus''
| sucrose
| '''Glu201'''
| Asp22
| <cite>Verhaest2007</cite>
|-
| [[GH33]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1s0i 1s0i]
| transsialidase
| ''Trypanosoma cruzi''
| sialyllactose
| '''Asp59'''
| Tyr342
| <cite>Amaya2004</cite>
|-
| [[GH34]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzw 4gzw]
| N2 neuraminidase
| ''Influenza'' A Tanzania/205/2010 H3N2
| α-{{Smallcaps|d}}-Neup5Ac-(2,3)-β-{{Smallcaps|d}}-Galp-(1,4)-β-{{Smallcaps|d}}-GlcpNAc
| '''Asp151'''
| Tyr406
| <cite>Zhu2012</cite>
|-
| [[GH35]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3ogv 3ogv]
| β-galactosidase
| ''Hypocrea jecorina''
| 2-phenylethyl 1-thio-β-{{Smallcaps|d}}-galactopyranoside
| '''Glu200'''
| Glu298
| <cite>Maksimainen2011</cite>
|-
| [[GH36]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4fnu 4fnu]
| β-galactosidase
| ''Geobacillus stearothermophilus''
| stachyose
| '''Asp584'''
| Asp478
| <cite>Merceron2012</cite>
|-
| [[GH37]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2jf4 2jf4]
| trehalase
| ''Escherichia coli''
| validoxylamine
| '''Asp312'''
| Glu496
| <cite>Gibson2007</cite>
|-
| [[GH38]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3czn 3czn]
| Golgi α-mannosidase II
| ''Drosophila melanogaster''
| GlcNAcMan(5)GlcNAc(2)
| '''Asp341'''
| Asp204
| <cite>Shah2008</cite>
|-
| [[GH39]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2bfg 2bfg]
| β-xylosidase
| ''Geobacillus stearothermophilus''
| 2,5-dinitrophenyl-β-{{Smallcaps|d}}-xyloside
| '''Glu160'''
| Glu278
| <cite>Czjzek2005</cite>
|-
| [[GH42]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ucf 4ucf]
| β-galactosidase
| ''Bifidobacterium bifidum''
| {{Smallcaps|d}}-galactose
| '''Glu161'''
| Glu320
| <cite>Godoy2016</cite>
|-
| [[GH43]]
| F
| 5-fold β-propeller
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3akh 3akh]
| exo-1,5-α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces avermitilis''
| α-1,5-arabinofuranotriose
| '''Glu196'''
| Asp220
| <cite>Fujimoto2010</cite>
|-
| [[GH44]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2eqd 2eqd]
| endoglucanase
| ''Clostridium thermocellum''
| cellooctaose
| '''Glu186'''
| Glu359
| <cite>Kitago2007</cite>
|-
| [[GH45]]
| none
| 6-stranded β-barrel
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4eng 4eng]
| endo-1,4-glucanase
| ''Humicola insolens''
| cellohexaose
| '''Asp121'''
| Asp10
| <cite>Davies1996</cite>
|-
| [[GH46]]
| I
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4olt 4olt]
| chitosanase
| ''Microbacterium sp.'' OU01
| hexa-glucosamine
| '''Glu25'''
| Asp43
| <cite>Lyu2014</cite>
|-
| [[GH47]]
| none
| (α/α)7
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1x9d 1x9d]
| α-mannosidase I
| ''Homo sapiens''
| Me-2-S-(α-Man)-2-thio-α-Man
| '''Asp463'''
| Glu599
| <cite>Karaveg2005</cite>, <cite>Nerinckx2008</cite>
|-
| [[GH48]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH8''
|
|
|
|
|
|
|-
| [[GH49]]
| N
| β-helix
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH28''
|
|
|
|
|
|
|-
| [[GH50]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4bq5 4bq5]
| exo-β-agarase
| ''Saccharophagus degradans''
| neoagarotetraose
| '''Glu535'''
| Glu695
| <cite>Pluvinage2013</cite>
|-
| [[GH51]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1qw9 1qw9]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Geobacillus stearothermophilus''
| PNP-{{Smallcaps|l}}-arabinofuranoside
| '''Glu175'''
| Glu294
| <cite>Hoevel2003</cite>
|-
| [[GH52]]
| O
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4c1p 4c1p]
| β-xylosidase
| ''Geobacillus thermoglucosidasius''
| xylobiose
| '''Asp517'''
| Glu537
| <cite>Espina2014</cite>
|-
| [[GH53]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2ccr 2ccr]
| β-1,4-galactanase
| ''Bacillus licheniformis''
| galactotriose
| '''Glu165'''
| Glu263
| <cite>Le_Nours2009</cite>
|-
| [[GH54]]
| none
| β-sandwich
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1wd4 1wd4]
| α-{{Smallcaps|l}}-arabinofuranosidase B
| ''Aspergillus kawachii''
| {{Smallcaps|l}}-arabinofuranose
| '''Asp297'''
| Glu221
| <cite>Miyanaga2004</cite>
|-
| [[GH55]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4tz5 4tz5]
| exo-β-1,3-glucanase
| ''Streptomyces sp.'' SirexAA-E
| laminarihexaose
| '''Glu502'''
| unknown
| <cite>Bianchetti2015</cite>
|-
| [[GH56]]
| none
| (β/α)7
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1fcv 1fcv]
| hyaluronidase
| ''Apis mellifera''
| (hyaluron.)4
| '''Glu113'''
| internal
| <cite>Markovic-Housley2000</cite>
|-
| [[GH57]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1k1y 1k1y]
| glucanotransferase
| ''Thermococcus litoralis''
| acarbose
| '''Asp214'''
| Glu123
| <cite>Imamura2003</cite>
|-
| [[GH59]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ccc 4ccc]
| β-galactocerebrosidase
| ''Mus musculus''
| PNP-β-{{Smallcaps|d}}-galactoside
| '''Glu182'''
| Glu258
| <cite>Hill2013</cite>
|-
| [[GH62]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3wn0 3wn0]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces coelicolor''
| β-{{Smallcaps|l}}-Arabinofuranose
| '''Glu361'''
| Asp202
| <cite>Maehara2014</cite>
|-
| [[GH63]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5ca3 5ca3]
| α-glucosidase
| ''Escherichia coli''
| glucose and lactose
| '''Asp501'''
| Glu727
| <cite>Miyazaki2016</cite>
|-
| [[GH65]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}4ktr 4ktr]
| 2-O-α-glucosylglycerol phosphorylase
| ''Bacillus selenitireducens''
| isofagomine
| '''Glu475'''
| phosphate
| <cite>Touhara2014</cite>
|-
| [[GH66]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5axh 5axh]
| dextranase
| ''Thermoanaerobacter pseudethanolicus''
| isomaltohexaose
| '''Glu374'''
| Asp312
| <cite>Suzuki2016</cite>
|-
| [[GH67]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1l8n 1l8n]
| α-glucuronidase
| ''Geobacillus stearothermophilus''
| 4-O-methyl-{{Smallcaps|d}}-glucuronic acid and xylotriose
| '''Glu286'''
| Asp364 Glu392
| <cite>Golan2004</cite>
|-
| [[GH68]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1pt2 1pt2]
| levansucrase
| ''Bacillus subtilis''
| sucrose
| '''Glu342'''
| Asp86
| <cite>Meng2003</cite>
|-
| [[GH70]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3aic 3aic]
| glucansucrase
| ''Streptococcus mutans''
| α-acarbose
| '''Glu515'''
| Asp477
| <cite>Ito2011</cite>
|-
| [[GH72]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w62 2w62]
| β-1,3-glucanotransferase
| ''Saccharomyces cerevisiae'' S288C
| laminaripentaose
| '''Glu176'''
| Glu275
| <cite>Hurtado-Gerrero2009</cite>
|-
| [[GH74]]
| none
| 7-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}2ebs 2ebs]
| cellobiohydrolase (OXG-RCBH)
| ''Geotrichum sp.'' m128
| xyloglucan heptasaccharide
| '''Asp465'''
| Asp35
| <cite>Yaoi2007</cite>
|-
| [[GH76]]
| none
| (α/α)6
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5agd 5agd]
| endo-α-1,6-mannanase
| ''Bacillus circulans''
| α-1,6-mannopentaose
| '''Asp125'''
| Asp124
| <cite>Thompson2015</cite>
|-
| [[GH77]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2oww 2oww]
| 4-α-glucanotransferase
| ''Thermus thermofilus''
| acarbose + 4-deoxy-α-{{Smallcaps|d}}-glucose
| '''Glu340'''
| Asp293
| <cite>Barends2007</cite>
|-
| [[GH78]]
| H
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3w5n 3w5n]
| α-{{Smallcaps|l}}-rhamnosidase
| ''Streptomyces avermitilis''
| {{Smallcaps|l}}-rhamnose
| '''Glu636'''
| Glu895
| <cite>Fujimoto2013</cite>
|-
| [[GH79]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5e9c 5e9c]
| heparanase
| ''Homo sapiens''
| heparin tetrasaccharide
| '''Glu225'''
| Glu343
| <cite>Wu2015</cite>
|-
| [[GH80]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH24''
|
|
|
|
|
|
|-
| [[GH81]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5t4g 5t4g]
| endo-β-1,3-glucanase
| ''Bacillus halodurans'' C-125
| laminarin
| '''Asp466'''
| Glu542
| <cite>Pluvinage2017</cite>
|-
| [[GH83]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1z4x 1z4x]
| hemagglutinin-neuraminidase
| Simian virus 5
| α-2,3-sialyllactose
| '''Glu247''' relay
| Tyr523
| <cite>Yuan2005</cite>
|-
| [[GH84]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2chn 2chn]
| β-''N''-acetyl-glucosaminidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| NAG-thiazoline
| '''Glu242'''
| internal
| <cite>Dennis2006</cite>
|-
| [[GH85]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w92 2w92]
| endo-β-''N''-acetyl-glucosaminidase D
| ''Streptococcus pneumoniae'' TIGR4
| NAG-thiazoline
| '''Glu337'''
| internal
| <cite>Abbott2009</cite>
|-
| [[GH86]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4aw7 4aw7]
| β-porphyranase
| ''Bacteroides plebeius''
| porphyran fragment
| '''Glu152'''
| Glu279
| <cite>Hehemann_1_2012</cite>
|-
| [[GH89]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vcb 2vcb]
| α-''N''-acetyl-glucosaminidase
| ''Clostridium perfringens''
| PUGNAc
| '''Glu483'''
| Glu601
| <cite>Ficko-Blean2008</cite>
|-
| [[GH92]]
| none
| (α/α)6 and β-sandwich
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ww1 2ww1]
| α-1,2-mannosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| thiomannobioside
| '''Glu533'''
| Asp644 Asp642
| <cite>Zhu2009</cite>
|-
| [[GH93]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3a72 3a72]
| exo-arabinanase
| ''Penicillium chrysogenum''
| arabinobiose
| '''Glu246'''
| Glu174
| <cite>Sogabe2011</cite>
|-
| [[GH94]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4zli 4zli]
| cellobionic acid phosphorylase
| ''Saccharophagus degradans''
| 3-O-β-{{Smallcaps|d}}-glucopyranosyl-α-{{Smallcaps|d}}-glucopyranuronic acid
| '''Asp472'''
| phosphate
| <cite>Nam2015</cite>
|-
| [[GH95]]
| none
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ead 2ead]
| α-1,2-{{Smallcaps|l}}-fucosidase
| ''Bifidobacterium bifidum''
| Fuc-α-1,2-Gal
| '''Glu566'''
| Asn423 Asp766
| <cite>Nagae2007</cite>
|-
| [[GH97]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining + inverting
| '''''anti'''''
| [{{PDBlink}}2zq0 2zq0]
| α-glucosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| acarbose
| '''Glu532'''
| Glu508
| <cite>Kitamura2008</cite>
|-
| [[GH98]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2wmg 2wmg]
| endo-β-1,4-galactosidase
| ''Streptococcus pneumoniae''
| A-LewisY pentasaccharide
| '''Glu158'''
| Asp251 Glu301
| <cite>Higgins2009</cite>
|-
| [[GH99]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ad4 4ad4]
| endo-α-mannosidase
| ''Bacteroides xylanisolvens''
| glucose-1,3-isofagomine and α-1,2- mannobiose
| '''Glu336'''
| debated
| <cite>Thompson2012</cite>
|-
| [[GH100]]
| none
| (α/α)6 core
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5gop 5gop]
| invertase
| ''Anabaena (Nostoc) sp.'' pcc7120
| sucrose
| '''Asp188'''
| Glu414
| <cite>Xie2016</cite>
|-
| [[GH102]]
| none
| double-ψ β-barrel
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}2pi8 2pi8]
| lytic transglycosylase A
| ''Escherichia coli''
| chitohexaose
| '''Asp308'''
| none
| <cite>van_Straaten2007</cite>
|-
| [[GH103]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1d0k 1d0k]
| lytic transglycosylase SLT35
| ''Escherichia coli''
| murodipeptides
| '''Glu162'''
| internal
| <cite>van_Asselt2000</cite>
|-
| [[GH106]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5mwk 5mwk]
| α-{{Smallcaps|l}}-rhamnosidase BT_0986
| ''Bacteroides thetaiotaomicron''
| pectin heptasaccharide
| '''Glu461'''
| Glu593 or Glu561
| <cite>Ndeh2017</cite>
|-
| [[GH107]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| ''predicted syn by clan''
| ''see at GH29''
|
|
|
|
|
|
|-
| [[GH110]]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}7jwf 7jwf]
| α-1,3-galactosidase
| ''Pseudoalteromonas distincta''
| Gal-α1,3-Gal
| '''Asp344'''
| Asp321 Asp345
| <cite>McGuire2020</cite>
|-
| [[GH113]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4cd8 4cd8]
| β-mannanase
| ''Alicyclobacillus acidocaldarius''
| mannobioimidazole
| '''Glu151'''
| Glu231
| <cite>Williams2014</cite>
|-
| [[GH116]]
| O
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at GH52''
|
|
|
|
|
|
|-
| [[GH117]]
| none
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}4ak7 4ak7]
| α-1,3-3,6-anhydro-{{Smallcaps|l}}-galactosidase
| ''Bacteroides plebeius''
| neoagarobiose
| '''His302''' (relay from Asp320)
| Asp90
| <cite>Hehemann_2_2012</cite>
|-
| [[GH120]]
| none
| parallel β-helix and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3vsv 3vsv]
| β-xylosidase XylC
| ''Thermoanaerobacterium saccharolyticum'' JW/SL-YS485
| {{Smallcaps|d}}-xylose
| '''Glu405'''
| Asp382
| <cite>Huang2012</cite>
|-
| [[GH123]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5fr0 5fr0]
| exo-β-N-acetyl-galactosaminidase
| ''Clostridium perfringens''
| ''N''-difluoroacetyl-{{Smallcaps|d}}-galactosamine
| '''Glu345'''
| internal
| <cite>Noach2016</cite>
|-
| [[GH125]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5m7y 5m7y]
| exo-α-1,6-mannosidase
| ''Clostridium perfringens''
| 1,6-α-mannotriose
| '''Asp220'''
| Glu393
| <cite>Alonso-Gil2016</cite>
|-
| [[GH127]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3wrg 3wrg]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bifidobacterium longum''
| {{Smallcaps|l}}-arabinose
| '''Glu322'''
| Cys417
| <cite>Huang2014</cite>
|-
| [[GH128]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}6ufl 6ufl]
| β-1,3-glucanase
| ''Amycolatopsis mediterranei''
| laminarihexaose
| '''Glu102'''
| Glu199
| <cite>Santos2020</cite>
|-
| [[GH130]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5b0s 5b0s]
| β-1,2-mannobiose phosphorylase
| ''Listeria innocua''
| β-1,2-mannotriose
| '''Asp141''' relay
| phosphate
| <cite>Tsuda2015</cite>
|-
| [[GH134]]
| none
| β + α
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5jug 5jug]
| β-mannanase
| ''Streptomyces sp.''
| mannopentaose
| '''Glu45'''
| Asp57
| <cite>Jin2016</cite>
|-
| [[GH136]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}5gqf 5gqf]
| lacto-N-biosidase
| ''Bifidobacterium longum''
| lacto-N-biose
| '''Asp411'''
| Asp418
| <cite>Yamada2017</cite>
|-
| [[GH137]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|l}}
| unknown
| '''''anti'''''
| [{{PDBlink}}5mui 5mui]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0996
| ''Bacteroides thetaiotaomicron''
| pectin oligosaccharide
| '''Glu240'''
| Glu159
| <cite>Ndeh2017</cite>
|-
| [[GH138]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}6hzg 6hzg]
| α-1,2-{{Smallcaps|d}}-galacturonidase
| ''Bacteroides paurosaccharolyticus''
| alpha-{{Smallcaps|d}}-galactopyranuronic
| '''Glu294'''
| Glu361
| <cite>Labourel2019</cite>
|-
| [[GH146]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5opj 5opj]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0349
| ''Bacteroides thetaiotaomicron''
| {{Smallcaps|l}}-arabinose
| '''Glu320'''
| Cys416
| <cite>Luis2018</cite>
|-
| [[GH147]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH148]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH149]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH156]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}6s0e 6s0e]
| exo-α-sialidase
| uncultured bacterium pG7
| N-acetyl-2,3-dehydro-2-deoxyneuraminic acid
| '''His134''' (relay from Asp132)
| Asp14
| <cite>Bule2019</cite>
|-
| [[GH157]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH158]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH161]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH162]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}6imw 6imw]
| endo-β-1,2-glucanase
| ''Talaromyces funiculosus''
| beta-1,2-glucan
| '''Glu262''' via C3-OH of glc at subs. +2
| Asp446
| <cite>Tanaka2019</cite>
|-
| [[GH164]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}6t75 6t75]
| β-mannosidase
| ''Bacteroides salyersiae''
| 2-deoxy-2-F-mannosyl
| '''Glu160'''
| Glu297
| <cite>Armstrong2020</cite>
|-
| [[GH172]]
| none
| β-jelly roll
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}7v1w 7v1w]
| difructose-anhydride synthase
| ''Bifidobacterium dentum''
| beta-{{Smallcaps|d}}-arabinofuranose
| '''Glu270'''
| Glu291
| <cite>Kashima2021</cite>
|-
| [http://www.cazy.org/GH0.html n.c.*]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2vjj 2vjj]
| endo-α-N-acetylglucosaminidase
| Bacteriophage HK620
| O18A1 O-antigen hexasaccharide
| '''Asp339'''
| Glu372
| <cite>Barbirz2008</cite>
|}
<nowiki>*</nowiki> n.c.: Found among the collection of [http://www.cazy.org/GH0.html non-classified GH sequences in the CAZy Database].

== References ==

<biblio>
# HeightmanVasella1999 Heightman TD and Vasella AT. ''Recent Insights into Inhibition, Structure, and Mechanism of Configuration-Retaining Glycosidases.'' Angew Chem Int Ed. 1999 38(6):750-770. [http://www3.interscience.wiley.com/journal/55000581/abstract Article online].
# Nerinckx2005 pmid=15642336
# Wu2012 pmid=23137336
# Perez1978 Pérez S and Marchessault RH. ''The exo-anomeric effect: experimental evidence from crystal structures.'' Carbohydr res. 1978 65:114-120. [http://dx.doi.org/10.1016/S0008-6215(00)84218-4 DOI:10.1016/S0008-6215(00)84218-4]
# Cramer1997 Cramer CJ, Truhlar DG, and French AD. ''Exo-anomeric effects on energies and geometries of different conformations of glucose and related systems in the gas phase and aqueous solution.'' Carbohydr res. 1997 298:1-14. [http://dx.doi.org/10.1016/S0008-6215(96)00297-2 DOI:10.1016/S0008-6215(96)00297-2]
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# Rajan2004 pmid=15341727
# Varrot2003 pmid=12595701
# Zhou1999 pmid=10508787
# Sulzenbacher1999 pmid=10200171
# Urbanikova2011 pmid=21501386
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# Schubot2004 pmid=14756552
# Suzuki2009 pmid=19279191
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# Sandgren2004 pmid=15364577
# Uitdehaag1999 pmid=10331869
# Miyake2003 pmid=12741813
# Harris1993 pmid=8431441
# Allouch2004 pmid=15062085
# Wojtkowiak2013 pmid=23275163
# Papanikolau2001 pmid=11560481
# Prag2000 pmid=10884356
# Vocadlo2001 pmid=11518970
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# Baldwin1993 pmid=8259514
# Cartmell2008 pmid=18799462
# Fernandez-Leiro2010 pmid=20592022
# Abbott2007 pmid=17397864
# Sakurama2012 pmid=22451675
# Sim2008 pmid=18036614
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# Maksimainen2011 pmid=21130883
# Merceron2012 pmid=23012371
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# Shah2008 pmid=18599462
# Czjzek2005 pmid=16212978
# Godoy2016 pmid=27685756
# Fujimoto2010 pmid=20739278
# Kitago2007 pmid=17905739
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# Karaveg2005 pmid=15713668
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# Pluvinage2013 pmid=23921382
# Yuan2005 pmid=15893670
# Hoevel2003 pmid=14517232
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</biblio>

[[Category:Definitions and explanations]]

Syn/anti lateral protonation

2021-11-18T15:06:22Z

Wim Nerinckx: Added anti-protonators GH128 and 172

{{CuratorApproved}}
* [[Author]]: ^^^Wim Nerinckx^^^
* [[Responsible Curator]]: ^^^Spencer Williams^^^

----

== Overview ==

This page provides a table that summarizes the spatial positioning of the catalytic [[general acid]] residue in the active sites of [[glycoside hydrolase]]s, relative to the substrate. The table below updates those found in the seminal paper on this concept by Heightman and Vasella <cite>HeightmanVasella1999</cite>, and a following paper by Nerinckx ''et al.'' <cite>Nerinckx2005</cite>.

== Background ==

The ''"not from above, but from the side"'' concept of semi-lateral glycosidic oxygen [[General_acid/base|protonation]] by [[glycoside hydrolase]]s was introduced by Heightman and Vasella <cite>HeightmanVasella1999</cite>. It was originally only described for [[Anomeric centre (alpha and beta)|beta]]-equatorial [[glycoside hydrolase]]s, but appears to be equally applicable to enzymes acting on an [[Anomeric centre (alpha and beta)|alpha]]-axial glycosidic bond <cite>Nerinckx2005</cite>. When dividing [[Sub-site nomenclature|subsite -1]] into half-spaces by a plane defined by the glycosidic oxygen and C1' and H1' of the –1 glycoside, many ligand-complexed structures reveal that the [[General_acid/base|proton donor]] is positioned either in the ''syn'' half-space (near the ring-oxygen of the –1 glycoside), or in the ''anti'' half-space (on the opposite side of the ring-oxygen). Members of the same GH [[Families|family]] appear to share a common ''syn'' or ''anti'' [[General_acid/base|protonator]] arrangement and further, this specificity appears to be preserved within [[Clans|Clans]] of [[Families|families]]. This page's compilation of [[Sub-site nomenclature|subsite -1]] occupied complexes shows that about 70% of all GH [[Families|families]] are ''anti'' [[General_acid/base|protonators]].

Closer inspection of crystal structures of [[Sub-site nomenclature|–1/+1 subsite]]-spanning substrates, or substrate-analogue ligands, in complex with enzymes reveals a further intriguing corollary <cite>Nerinckx2005 Wu2012</cite>. In substrate-bound complexes with ''anti'' [[General_acid/base|protonating]] GH enzymes, the scissile [[Anomeric centre (alpha and beta)|anomeric bond]] (often studied using the thio-analogue) shows a dihedral angle φ (O5'-C1'-[O,S]x-Cx) that is in the lowest-energy synclinal (gauche) conformation. The rationale for this is that a minus synclinal dihedral angle φ for an equatorial glycosidic bond, or plus synclinal for an axial glycosidic bond <cite>Perez1978</cite>, allows for hyperconjugative overlap of the C1'-O5' antibonding orbital with an antiperiplanar-oriented lone pair orbital lobe of the glycosidic oxygen, thereby creating partial double bond character and stabilization of the glycosidic bond by 4–5 kcal/mol; this ground-state stabilizing phenomenon is known as the ‘exo-anomeric effect’ <cite>Cramer1997 Johnson2009 Alonso2016</cite>. ''Anti'' [[General_acid/base|protonation]] occurs on the glycosidic oxygen’s antiperiplanar lone pair, thereby removing the stabilizing exo-anomeric effect. This suggests that ''anti'' [[General_acid/base|protonation]] is an enzymic approach for lowering the activation barrier leading to the [[Transition state|transition state]] (Figure 1 centre).

''Syn'' [[General_acid/base|protonating]] [[glycoside hydrolase]]s apparently make use of a different approach <cite>Nerinckx2005 Wu2012</cite>. In many [[Sub-site nomenclature|–1/+1 subsite]]-spanning ligand complexes, the dihedral angle φ of the scissile anomeric bond has been rotated away from its lowest-energy synclinal position: clockwise to minus-anticlinal or antiperiplanar for beta-equatorial; counterclockwise to plus-anticlinal or antiperiplanar for alpha-axial [[Anomeric centre (alpha and beta)|anomeric bonds]]. This removes the hyperconjugative overlap and thus also the stabilizing exo-anomeric effect. And because of this rotation, a lone pair of the glycosidic oxygen is directed into the ''syn'' half-space, allowing it to be protonated by the ''syn''-positioned [[General_acid/base|proton donor]] (Figure 1 right).

[[File:Syn_anti.jpg|800px|thumb|center|Figure 1. Newman projections, with the glycosidic oxygen as proximal atom and the anomeric carbon as distal atom, showing ''anti'' (centre) versus ''syn'' (right) semi-lateral [[General_acid/base|protonation]] in beta-equatorial (top) and alpha-axial (bottom) [[glycoside hydrolase]]s. The indicated φ is the dihedral angle for O5'-C1'-O4-C4.]]

== Table of ''syn/anti'' protonation examples ==

This table contains only one example per GH [[Families|family]] of a ligand-complexed protein structure where the ''syn'' or ''anti'' positioning of the [[General_acid/base|proton donor]] can be clearly observed; other examples may be available on a [[Families|family-by-family]] basis. The reader is thus advised to consult the [http://www.cazy.org/fam/acc_GH.html#table CAZy database] for a current, comprehensive list of CAZyme structures. Where available, the selected examples are Michaelis-type complexes with the ligand spanning the [[Sub-site nomenclature|-1/+1 subsites]], since these have an intact glycosidic or thioglycosidic bond, or are ''N''-analogs of the substrate (''e.g.'' acarbose). In some examples, the [[General_acid/base|proton donor]] has been mutated (''e.g.'', to the corresponding amide or to an alanine), and in those cases one may wish to look at a superposition of the given PDB example with the structure of the native enzyme. If a Michaelis-type complex is not yet available, the second and third example choices, respectively, are trapped glycosyl-enzyme [[intermediate]]s and product complexes where [[Sub-site nomenclature|subsite -1]] is occupied.

''Please also be aware that this is a large table with many data. Please contact the page Author or Responsible Curator with corrections.''

=== Table ===
This table can be re-sorted by clicking on the icons in the header (''javascript must be turned on in your browser''). To reset the page to be sorted by GH family, click the ''View'' tab at the very top of the page.

{| {{Prettytable}} class="sortable"
|- valign="top"
! '''Family'''
! '''Clan'''
! '''Structure fold '''
! '''Anomeric specificity'''
! '''Mechanism'''
! '''''Syn/anti'' protonator'''
! '''Example PDB ID'''
! '''Enzyme'''
! '''Organism'''
! '''Ligand'''
! '''General acid'''
! '''Nucleophile or General base'''
! '''Reference'''
|-
| [[GH1]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2cer 2cer]
| β-glycosidase S
| ''Sulfolobus solfataricus'' P2
| phenethyl glucoimidazole
| '''Glu206'''
| Glu387
| <cite>Gloster2006</cite>
|-
| [[GH2]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vzu 2vzu]
| exo-β-glucosaminidase
| ''Amicolatopsis orientalis''
| PNP-β-{{Smallcaps|d}}-glucosamine
| '''Glu469'''
| Glu541
| <cite>van_Bueren2009</cite>
|-
| [[GH3]]
| none
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1iex 1iex]
| exo-1,3-1,4-glucanase
| ''Hordeum vulgare''
| thiocellobiose
| '''Glu491'''
| Asp285
| <cite>Hrmova2001</cite>
|-
| [[GH4]]
| none
| Rossmann + α6/β3 + β3/α4
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1u8x 1u8x]
| 6-P-α-glucosidase
| ''Bacillus subtilis''
| alpha-{{Smallcaps|d}}-glucose-6-phosphate
| '''Asp172'''
| Not applicable
| <cite>Rajan2004</cite>
|-

| [[GH5]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1h2j 1h2j]
| endo-β-1,4-glucanase
| ''Bacillus agaradhaerens''
| 2',4'-DNP-2-F-cellobioside
| '''Glu129'''
| Glu228
| <cite>Varrot2003</cite>
|-
| [[GH6]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1qjw 1qjw]
| cellobiohydrolase 2
| ''Hypocrea jecorina''
| (Glc)2-S-(Glc)2
| '''Asp221'''
| debated
| <cite>Zhou1999</cite>
|-
| [[GH7]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1ovw 1ovw]
| endo-1,4-glucanase
| ''Fusarium oxysporum''
| thio-(Glc)5
| '''Glu202'''
| Glu197
| <cite>Sulzenbacher1999</cite>
|-
| [[GH8]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1kwf 1kwf]
| endo-1,4-glucanase
| ''Clostridium thermocellum''
| cellopentaose
| '''Glu95'''
| Asp278
| <cite>Guerin2002</cite>
|-
| [[GH9]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1rq5 1rq5]
| cellobiohydrolase
| ''Clostridium thermocellum''
| cellotetraose
| '''Glu795'''
| Asp383
| <cite>Schubot2004</cite>
|-
| [[GH10]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2d24 2d24]
| β-1,4-xylanase
| ''Streptomyces olivaceoviridis'' E-86
| xylopentaose
| '''Glu128'''
| Glu236
| <cite>Suzuki2009</cite>
|-
| [[GH11]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}4hk8 4hk8]
| endo-β-1,4-xylanase
| ''Hypocrea jecorina''
| xylohexaose
| '''Glu177'''
| Glu86
| <cite>Wan2014</cite>
|-
| [[GH12]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1w2u 1w2u]
| endoglucanase
| ''Humicola grisea''
| thiocellotetraose
| '''Glu205'''
| Glu120
| <cite>Sandgren2004</cite>
|-
| [[GH13]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1cxk 1cxk]
| β-cyclodextrin glucanotransferase
| ''Bacillus circulans''
| maltononaose
| '''Glu257'''
| Asp229
| <cite>Uitdehaag1999</cite>
|-
| [[GH14]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1itc 1itc]
| β-amylase
| ''Bacillus cereus''
| maltopentaose
| '''Glu172'''
| Glu367
| <cite>Miyake2003</cite>
|-
| [[GH15]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1dog 1dog]
| glucoamylase
| ''Aspergillus awamori''
| 1-deoxynojirimycin
| '''Glu179'''
| Glu400
| <cite>Harris1993</cite>
|-
| [[GH16]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1urx 1urx]
| β-agarase A
| ''Zobellia galactanivorans''
| oligoagarose
| '''Glu152'''
| Glu147
| <cite>Allouch2004</cite>
|-
| [[GH17]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzj 4gzj]
| endo-β-1,3-glucanase
| ''Solanum tuberosum''
| laminaratriose + laminarabiose
| '''Glu118'''
| Glu259
| <cite>Wojtkowiak2013</cite>
|-
| [[GH18]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1ffr 1ffr]
| chitinase A
| ''Serratia marcescens''
| (NAG)6
| '''Glu315'''
| internal
| <cite>Papanikolau2001</cite>
|-
| [[GH19]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}3wh1 3wh1]
| chitinase
| ''Bryum coronatum''
| (GlcNAc)4
| '''Glu61'''
| Glu70
| <cite>Ohnuma2014</cite>
|-
| [[GH20]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1c7s 1c7s]
| chitobiase
| ''Serratia marcescens''
| chitobiose
| '''Glu540'''
| internal
| <cite>Prag2000</cite>
|-
| [[GH22]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1h6m 1h6m]
| lysozyme C
| ''Gallus gallus''
| Chit-2-F-chitosyl
| '''Glu35'''
| Asp52
| <cite>Vocadlo2001</cite>
|-
| [[GH23]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1lsp 1lsp]
| lysozyme G
| ''Cygnus atratus''
| Bulgecin A
| '''Glu73'''
| internal
| <cite>Karlsen1996</cite>
|-
| [[GH24]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}148l 148l]
| lysozyme E
| Bacteriophage T4
| chitobiosyl
| '''Glu11'''
| Glu26
| <cite>Baldwin1993</cite>
|-
| [[GH26]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vx6 2vx6]
| exo-β-mannanase
| ''Cellvibrio japonicus'' Ueda107
| Gal1Man4
| '''Glu221'''
| Glu338
| <cite>Cartmell2008</cite>
|-
| [[GH27]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}} / beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3lrm 3lrm]
| α-galactosidase
| ''Saccharomyces cerevisiae''
| raffinose
| '''Asp209'''
| Asp141
| <cite>Fernandez-Leiro2010</cite>
|-
| [[GH28]]
| N
| β-helix
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}2uvf 2uvf]
| exo-polygalacturonosidase
| ''Yersinia enterocolitica'' ATCC9610D
| digalacturonic acid
| '''Asp402'''
| Asp381 Asp403
| <cite>Abbott2007</cite>
|-
| [[GH29]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| '''''syn'''''
| [{{PDBlink}}3uet 3uet]
| α-1,3/4-fucosidase
| ''Bifidobacterium longum'' subsp. infantis
| lacto-''N''-fucopentaose II
| '''Glu217'''
| Asp172
| <cite>Sakurama2012</cite>
|-
| [[GH30]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2y24 2y24]
| glucurono-xylanase
| ''Dickea chrysanthemi'' D1
| glucuronoxylan tetrasaccharide
| '''Glu163'''
| Glu253
| <cite>Urbanikova2011</cite>
|-
| [[GH31]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2qmj 2qmj]
| maltase-glucoamylase
| ''Homo sapiens''
| acarbose
| '''Asp542'''
| Asp443
| <cite>Sim2008</cite>
|-
| [[GH32]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2add 2add]
| fructan β-(2,1)-fructosidase
| ''Cichorium intybus''
| sucrose
| '''Glu201'''
| Asp22
| <cite>Verhaest2007</cite>
|-
| [[GH33]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1s0i 1s0i]
| transsialidase
| ''Trypanosoma cruzi''
| sialyllactose
| '''Asp59'''
| Tyr342
| <cite>Amaya2004</cite>
|-
| [[GH34]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzw 4gzw]
| N2 neuraminidase
| ''Influenza'' A Tanzania/205/2010 H3N2
| α-{{Smallcaps|d}}-Neup5Ac-(2,3)-β-{{Smallcaps|d}}-Galp-(1,4)-β-{{Smallcaps|d}}-GlcpNAc
| '''Asp151'''
| Tyr406
| <cite>Zhu2012</cite>
|-
| [[GH35]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3ogv 3ogv]
| β-galactosidase
| ''Hypocrea jecorina''
| 2-phenylethyl 1-thio-β-{{Smallcaps|d}}-galactopyranoside
| '''Glu200'''
| Glu298
| <cite>Maksimainen2011</cite>
|-
| [[GH36]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4fnu 4fnu]
| β-galactosidase
| ''Geobacillus stearothermophilus''
| stachyose
| '''Asp584'''
| Asp478
| <cite>Merceron2012</cite>
|-
| [[GH37]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2jf4 2jf4]
| trehalase
| ''Escherichia coli''
| validoxylamine
| '''Asp312'''
| Glu496
| <cite>Gibson2007</cite>
|-
| [[GH38]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3czn 3czn]
| Golgi α-mannosidase II
| ''Drosophila melanogaster''
| GlcNAcMan(5)GlcNAc(2)
| '''Asp341'''
| Asp204
| <cite>Shah2008</cite>
|-
| [[GH39]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2bfg 2bfg]
| β-xylosidase
| ''Geobacillus stearothermophilus''
| 2,5-dinitrophenyl-β-{{Smallcaps|d}}-xyloside
| '''Glu160'''
| Glu278
| <cite>Czjzek2005</cite>
|-
| [[GH42]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ucf 4ucf]
| β-galactosidase
| ''Bifidobacterium bifidum''
| {{Smallcaps|d}}-galactose
| '''Glu161'''
| Glu320
| <cite>Godoy2016</cite>
|-
| [[GH43]]
| F
| 5-fold β-propeller
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3akh 3akh]
| exo-1,5-α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces avermitilis''
| α-1,5-arabinofuranotriose
| '''Glu196'''
| Asp220
| <cite>Fujimoto2010</cite>
|-
| [[GH44]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2eqd 2eqd]
| endoglucanase
| ''Clostridium thermocellum''
| cellooctaose
| '''Glu186'''
| Glu359
| <cite>Kitago2007</cite>
|-
| [[GH45]]
| none
| 6-stranded β-barrel
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4eng 4eng]
| endo-1,4-glucanase
| ''Humicola insolens''
| cellohexaose
| '''Asp121'''
| Asp10
| <cite>Davies1996</cite>
|-
| [[GH46]]
| I
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4olt 4olt]
| chitosanase
| ''Microbacterium sp.'' OU01
| hexa-glucosamine
| '''Glu25'''
| Asp43
| <cite>Lyu2014</cite>
|-
| [[GH47]]
| none
| (α/α)7
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1x9d 1x9d]
| α-mannosidase I
| ''Homo sapiens''
| Me-2-S-(α-Man)-2-thio-α-Man
| '''Asp463'''
| Glu599
| <cite>Karaveg2005</cite>, <cite>Nerinckx2008</cite>
|-
| [[GH48]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH8''
|
|
|
|
|
|
|-
| [[GH49]]
| N
| β-helix
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH28''
|
|
|
|
|
|
|-
| [[GH50]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4bq5 4bq5]
| exo-β-agarase
| ''Saccharophagus degradans''
| neoagarotetraose
| '''Glu535'''
| Glu695
| <cite>Pluvinage2013</cite>
|-
| [[GH51]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1qw9 1qw9]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Geobacillus stearothermophilus''
| PNP-{{Smallcaps|l}}-arabinofuranoside
| '''Glu175'''
| Glu294
| <cite>Hoevel2003</cite>
|-
| [[GH52]]
| O
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4c1p 4c1p]
| β-xylosidase
| ''Geobacillus thermoglucosidasius''
| xylobiose
| '''Asp517'''
| Glu537
| <cite>Espina2014</cite>
|-
| [[GH53]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2ccr 2ccr]
| β-1,4-galactanase
| ''Bacillus licheniformis''
| galactotriose
| '''Glu165'''
| Glu263
| <cite>Le_Nours2009</cite>
|-
| [[GH54]]
| none
| β-sandwich
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1wd4 1wd4]
| α-{{Smallcaps|l}}-arabinofuranosidase B
| ''Aspergillus kawachii''
| {{Smallcaps|l}}-arabinofuranose
| '''Asp297'''
| Glu221
| <cite>Miyanaga2004</cite>
|-
| [[GH55]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4tz5 4tz5]
| exo-β-1,3-glucanase
| ''Streptomyces sp.'' SirexAA-E
| laminarihexaose
| '''Glu502'''
| unknown
| <cite>Bianchetti2015</cite>
|-
| [[GH56]]
| none
| (β/α)7
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1fcv 1fcv]
| hyaluronidase
| ''Apis mellifera''
| (hyaluron.)4
| '''Glu113'''
| internal
| <cite>Markovic-Housley2000</cite>
|-
| [[GH57]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1k1y 1k1y]
| glucanotransferase
| ''Thermococcus litoralis''
| acarbose
| '''Asp214'''
| Glu123
| <cite>Imamura2003</cite>
|-
| [[GH59]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ccc 4ccc]
| β-galactocerebrosidase
| ''Mus musculus''
| PNP-β-{{Smallcaps|d}}-galactoside
| '''Glu182'''
| Glu258
| <cite>Hill2013</cite>
|-
| [[GH62]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3wn0 3wn0]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces coelicolor''
| β-{{Smallcaps|l}}-Arabinofuranose
| '''Glu361'''
| Asp202
| <cite>Maehara2014</cite>
|-
| [[GH63]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5ca3 5ca3]
| α-glucosidase
| ''Escherichia coli''
| glucose and lactose
| '''Asp501'''
| Glu727
| <cite>Miyazaki2016</cite>
|-
| [[GH65]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}4ktr 4ktr]
| 2-O-α-glucosylglycerol phosphorylase
| ''Bacillus selenitireducens''
| isofagomine
| '''Glu475'''
| phosphate
| <cite>Touhara2014</cite>
|-
| [[GH66]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5axh 5axh]
| dextranase
| ''Thermoanaerobacter pseudethanolicus''
| isomaltohexaose
| '''Glu374'''
| Asp312
| <cite>Suzuki2016</cite>
|-
| [[GH67]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1l8n 1l8n]
| α-glucuronidase
| ''Geobacillus stearothermophilus''
| 4-O-methyl-{{Smallcaps|d}}-glucuronic acid and xylotriose
| '''Glu286'''
| Asp364 Glu392
| <cite>Golan2004</cite>
|-
| [[GH68]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1pt2 1pt2]
| levansucrase
| ''Bacillus subtilis''
| sucrose
| '''Glu342'''
| Asp86
| <cite>Meng2003</cite>
|-
| [[GH70]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3aic 3aic]
| glucansucrase
| ''Streptococcus mutans''
| α-acarbose
| '''Glu515'''
| Asp477
| <cite>Ito2011</cite>
|-
| [[GH72]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w62 2w62]
| β-1,3-glucanotransferase
| ''Saccharomyces cerevisiae'' S288C
| laminaripentaose
| '''Glu176'''
| Glu275
| <cite>Hurtado-Gerrero2009</cite>
|-
| [[GH74]]
| none
| 7-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}2ebs 2ebs]
| cellobiohydrolase (OXG-RCBH)
| ''Geotrichum sp.'' m128
| xyloglucan heptasaccharide
| '''Asp465'''
| Asp35
| <cite>Yaoi2007</cite>
|-
| [[GH76]]
| none
| (α/α)6
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5agd 5agd]
| endo-α-1,6-mannanase
| ''Bacillus circulans''
| α-1,6-mannopentaose
| '''Asp125'''
| Asp124
| <cite>Thompson2015</cite>
|-
| [[GH77]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2oww 2oww]
| 4-α-glucanotransferase
| ''Thermus thermofilus''
| acarbose + 4-deoxy-α-{{Smallcaps|d}}-glucose
| '''Glu340'''
| Asp293
| <cite>Barends2007</cite>
|-
| [[GH78]]
| H
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3w5n 3w5n]
| α-{{Smallcaps|l}}-rhamnosidase
| ''Streptomyces avermitilis''
| {{Smallcaps|l}}-rhamnose
| '''Glu636'''
| Glu895
| <cite>Fujimoto2013</cite>
|-
| [[GH79]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5e9c 5e9c]
| heparanase
| ''Homo sapiens''
| heparin tetrasaccharide
| '''Glu225'''
| Glu343
| <cite>Wu2015</cite>
|-
| [[GH80]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH24''
|
|
|
|
|
|
|-
| [[GH81]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5t4g 5t4g]
| endo-β-1,3-glucanase
| ''Bacillus halodurans'' C-125
| laminarin
| '''Asp466'''
| Glu542
| <cite>Pluvinage2017</cite>
|-
| [[GH83]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1z4x 1z4x]
| hemagglutinin-neuraminidase
| Simian virus 5
| α-2,3-sialyllactose
| '''Glu247''' relay
| Tyr523
| <cite>Yuan2005</cite>
|-
| [[GH84]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2chn 2chn]
| β-''N''-acetyl-glucosaminidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| NAG-thiazoline
| '''Glu242'''
| internal
| <cite>Dennis2006</cite>
|-
| [[GH85]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w92 2w92]
| endo-β-''N''-acetyl-glucosaminidase D
| ''Streptococcus pneumoniae'' TIGR4
| NAG-thiazoline
| '''Glu337'''
| internal
| <cite>Abbott2009</cite>
|-
| [[GH86]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4aw7 4aw7]
| β-porphyranase
| ''Bacteroides plebeius''
| porphyran fragment
| '''Glu152'''
| Glu279
| <cite>Hehemann_1_2012</cite>
|-
| [[GH89]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vcb 2vcb]
| α-''N''-acetyl-glucosaminidase
| ''Clostridium perfringens''
| PUGNAc
| '''Glu483'''
| Glu601
| <cite>Ficko-Blean2008</cite>
|-
| [[GH92]]
| none
| (α/α)6 and β-sandwich
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ww1 2ww1]
| α-1,2-mannosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| thiomannobioside
| '''Glu533'''
| Asp644 Asp642
| <cite>Zhu2009</cite>
|-
| [[GH93]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3a72 3a72]
| exo-arabinanase
| ''Penicillium chrysogenum''
| arabinobiose
| '''Glu246'''
| Glu174
| <cite>Sogabe2011</cite>
|-
| [[GH94]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4zli 4zli]
| cellobionic acid phosphorylase
| ''Saccharophagus degradans''
| 3-O-β-{{Smallcaps|d}}-glucopyranosyl-α-{{Smallcaps|d}}-glucopyranuronic acid
| '''Asp472'''
| phosphate
| <cite>Nam2015</cite>
|-
| [[GH95]]
| none
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ead 2ead]
| α-1,2-{{Smallcaps|l}}-fucosidase
| ''Bifidobacterium bifidum''
| Fuc-α-1,2-Gal
| '''Glu566'''
| Asn423 Asp766
| <cite>Nagae2007</cite>
|-
| [[GH97]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining + inverting
| '''''anti'''''
| [{{PDBlink}}2zq0 2zq0]
| α-glucosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| acarbose
| '''Glu532'''
| Glu508
| <cite>Kitamura2008</cite>
|-
| [[GH98]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2wmg 2wmg]
| endo-β-1,4-galactosidase
| ''Streptococcus pneumoniae''
| A-LewisY pentasaccharide
| '''Glu158'''
| Asp251 Glu301
| <cite>Higgins2009</cite>
|-
| [[GH99]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ad4 4ad4]
| endo-α-mannosidase
| ''Bacteroides xylanisolvens''
| glucose-1,3-isofagomine and α-1,2- mannobiose
| '''Glu336'''
| debated
| <cite>Thompson2012</cite>
|-
| [[GH100]]
| none
| (α/α)6 core
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5gop 5gop]
| invertase
| ''Anabaena (Nostoc) sp.'' pcc7120
| sucrose
| '''Asp188'''
| Glu414
| <cite>Xie2016</cite>
|-
| [[GH102]]
| none
| double-ψ β-barrel
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}2pi8 2pi8]
| lytic transglycosylase A
| ''Escherichia coli''
| chitohexaose
| '''Asp308'''
| none
| <cite>van_Straaten2007</cite>
|-
| [[GH103]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1d0k 1d0k]
| lytic transglycosylase SLT35
| ''Escherichia coli''
| murodipeptides
| '''Glu162'''
| internal
| <cite>van_Asselt2000</cite>
|-
| [[GH106]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5mwk 5mwk]
| α-{{Smallcaps|l}}-rhamnosidase BT_0986
| ''Bacteroides thetaiotaomicron''
| pectin heptasaccharide
| '''Glu461'''
| Glu593 or Glu561
| <cite>Ndeh2017</cite>
|-
| [[GH107]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| ''predicted syn by clan''
| ''see at GH29''
|
|
|
|
|
|
|-
| [[GH113]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4cd8 4cd8]
| β-mannanase
| ''Alicyclobacillus acidocaldarius''
| mannobioimidazole
| '''Glu151'''
| Glu231
| <cite>Williams2014</cite>
|-
| [[GH116]]
| O
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at GH52''
|
|
|
|
|
|
|-
| [[GH117]]
| none
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}4ak7 4ak7]
| α-1,3-3,6-anhydro-{{Smallcaps|l}}-galactosidase
| ''Bacteroides plebeius''
| neoagarobiose
| '''His302''' (relay from Asp320)
| Asp90
| <cite>Hehemann_2_2012</cite>
|-
| [[GH120]]
| none
| parallel β-helix and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3vsv 3vsv]
| β-xylosidase XylC
| ''Thermoanaerobacterium saccharolyticum'' JW/SL-YS485
| {{Smallcaps|d}}-xylose
| '''Glu405'''
| Asp382
| <cite>Huang2012</cite>
|-
| [[GH123]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5fr0 5fr0]
| exo-β-N-acetyl-galactosaminidase
| ''Clostridium perfringens''
| ''N''-difluoroacetyl-{{Smallcaps|d}}-galactosamine
| '''Glu345'''
| internal
| <cite>Noach2016</cite>
|-
| [[GH125]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5m7y 5m7y]
| exo-α-1,6-mannosidase
| ''Clostridium perfringens''
| 1,6-α-mannotriose
| '''Asp220'''
| Glu393
| <cite>Alonso-Gil2016</cite>
|-
| [[GH127]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3wrg 3wrg]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bifidobacterium longum''
| {{Smallcaps|l}}-arabinose
| '''Glu322'''
| Cys417
| <cite>Huang2014</cite>
|-
| [[GH128]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}6ufl 6ufl]
| β-1,3-glucanase
| ''Amycolatopsis mediterranei''
| laminarihexaose
| '''Glu102'''

| Glu199
| <cite>Santos2020</cite>
|-
| [[GH130]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5b0s 5b0s]
| β-1,2-mannobiose phosphorylase
| ''Listeria innocua''
| β-1,2-mannotriose
| '''Asp141''' relay
| phosphate
| <cite>Tsuda2015</cite>
|-
| [[GH134]]
| none
| β + α
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5jug 5jug]
| β-mannanase
| ''Streptomyces sp.''
| mannopentaose
| '''Glu45'''
| Asp57
| <cite>Jin2016</cite>
|-
| [[GH136]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}5gqf 5gqf]
| lacto-N-biosidase
| ''Bifidobacterium longum''
| lacto-N-biose
| '''Asp411'''
| Asp418
| <cite>Yamada2017</cite>
|-
| [[GH137]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|l}}
| unknown
| '''''anti'''''
| [{{PDBlink}}5mui 5mui]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0996
| ''Bacteroides thetaiotaomicron''
| pectin oligosaccharide
| '''Glu240'''
| Glu159
| <cite>Ndeh2017</cite>

|-
| [[GH138]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}6hzg 6hzg]
| α-1,2-{{Smallcaps|d}}-galacturonidase
| ''Bacteroides paurosaccharolyticus''
| alpha-{{Smallcaps|d}}-galactopyranuronic
| '''Glu294'''
| Glu361
| <cite>Labourel2019</cite>
|-
| [[GH146]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5opj 5opj]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0349
| ''Bacteroides thetaiotaomicron''
| {{Smallcaps|l}}-arabinose
| '''Glu320'''
| Cys416
| <cite>Luis2018</cite>
|-
| [[GH147]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH148]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH149]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH156]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}6s0e 6s0e]
| exo-α-sialidase
| uncultured bacterium pG7
| N-acetyl-2,3-dehydro-2-deoxyneuraminic acid
| '''His134''' (relay from Asp132)
| Asp14
| <cite>Bule2019</cite>

|-
| [[GH157]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-

| [[GH158]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH161]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH162]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}6imw 6imw]
| endo-β-1,2-glucanase
| ''Talaromyces funiculosus''
| beta-1,2-glucan
| '''Glu262''' via C3-OH of glc at subs. +2
| Asp446
| <cite>Tanaka2019</cite>
|-
| [[GH164]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}6t75 6t75]
| β-mannosidase
| ''Bacteroides salyersiae''
| 2-deoxy-2-F-mannosyl
| '''Glu160'''
| Glu297
| <cite>Armstrong2020</cite>
|-
| [[GH172]]
| none
| β-jelly roll
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}7v1w 7v1w]
| difructose-anhydride synthase
| ''Bifidobacterium dentum''
| beta-{{Smallcaps|d}}-arabinofuranose
| '''Glu270'''
| Glu291
| <cite>Kashima2021</cite>
|-
| [http://www.cazy.org/GH0.html n.c.*]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2vjj 2vjj]
| endo-α-N-acetylglucosaminidase
| Bacteriophage HK620
| O18A1 O-antigen hexasaccharide
| '''Asp339'''
| Glu372
| <cite>Barbirz2008</cite>
|}
<nowiki>*</nowiki> n.c.: Found among the collection of [http://www.cazy.org/GH0.html non-classified GH sequences in the CAZy Database].

== References ==

<biblio>
# HeightmanVasella1999 Heightman TD and Vasella AT. ''Recent Insights into Inhibition, Structure, and Mechanism of Configuration-Retaining Glycosidases.'' Angew Chem Int Ed. 1999 38(6):750-770. [http://www3.interscience.wiley.com/journal/55000581/abstract Article online].
# Nerinckx2005 pmid=15642336
# Wu2012 pmid=23137336
# Perez1978 Pérez S and Marchessault RH. ''The exo-anomeric effect: experimental evidence from crystal structures.'' Carbohydr res. 1978 65:114-120. [http://dx.doi.org/10.1016/S0008-6215(00)84218-4 DOI:10.1016/S0008-6215(00)84218-4]
# Cramer1997 Cramer CJ, Truhlar DG, and French AD. ''Exo-anomeric effects on energies and geometries of different conformations of glucose and related systems in the gas phase and aqueous solution.'' Carbohydr res. 1997 298:1-14. [http://dx.doi.org/10.1016/S0008-6215(96)00297-2 DOI:10.1016/S0008-6215(96)00297-2]
# Johnson2009 pmid=19733839
# Alonso2016 pmid=26889578
# Gloster2006 pmid=17002288
# van_Bueren2009 pmid=18976664
# Hrmova2001 pmid=11709165
# Rajan2004 pmid=15341727
# Varrot2003 pmid=12595701
# Zhou1999 pmid=10508787
# Sulzenbacher1999 pmid=10200171
# Urbanikova2011 pmid=21501386
# Guerin2002 pmid=11884144
# Schubot2004 pmid=14756552
# Suzuki2009 pmid=19279191
# Wan2014 pmid=24419374
# Sandgren2004 pmid=15364577
# Uitdehaag1999 pmid=10331869
# Miyake2003 pmid=12741813
# Harris1993 pmid=8431441
# Allouch2004 pmid=15062085
# Wojtkowiak2013 pmid=23275163
# Papanikolau2001 pmid=11560481
# Prag2000 pmid=10884356
# Vocadlo2001 pmid=11518970
# Karlsen1996 pmid=15299731
# Baldwin1993 pmid=8259514
# Cartmell2008 pmid=18799462
# Fernandez-Leiro2010 pmid=20592022
# Abbott2007 pmid=17397864
# Sakurama2012 pmid=22451675
# Sim2008 pmid=18036614
# Verhaest2007 pmid=17335500
# Amaya2004 pmid=15130470
# Zhu2012 pmid=23015718
# Maksimainen2011 pmid=21130883
# Merceron2012 pmid=23012371
# Gibson2007 pmid=17455176
# Shah2008 pmid=18599462
# Czjzek2005 pmid=16212978
# Godoy2016 pmid=27685756
# Fujimoto2010 pmid=20739278
# Kitago2007 pmid=17905739
# Davies1996 pmid=15299721
# Lyu2014 pmid=24766439
# Karaveg2005 pmid=15713668
# Nerinckx2008 pmid=18619586
# Pluvinage2013 pmid=23921382
# Yuan2005 pmid=15893670
# Hoevel2003 pmid=14517232
# Espina2014 pmid=24816105
# Le_Nours2009 pmid=19089956
# Miyanaga2004 pmid=15292273
# Bianchetti2015 pmid=25752603
# Markovic-Housley2000 pmid=11080624
# Imamura2003 pmid=12618437
# Hill2013 pmid=24297913
# Maehara2014 pmid=24482228
# Miyazaki2016 pmid=27688023
# Touhara2014 pmid=24828502
# Suzuki2016 pmid=26494689
# Golan2004 pmid=14573597
# Meng2003 pmid=14517548
# Ito2011 pmid=21354427
# Hurtado-Gerrero2009 pmid=19097997
# Yaoi2007 pmid=17498741
# Thompson2015 pmid=25772148
# Barends2007 pmid=17420245
# Fujimoto2013 pmid=23486481
# Wu2015 pmid=26575439
# Pluvinage2017 pmid=28781080
# Dennis2006 pmid=16565725
# Abbott2009 pmid=19181667
# Hehemann_1_2012 pmid=23150581
# Ficko-Blean2008 pmid=18443291
# Zhu2009 pmid=20081828
# Sogabe2011 pmid=21543843
# Nam2015 pmid=26041776
# Nagae2007 pmid=17459873
# Kitamura2008 pmid=18981178
# Higgins2009 pmid=19608744
# van_Straaten2007 pmid=17502382
# van_Asselt2000 pmid=10684641
# Ndeh2017 pmid=28329766
# Labourel2019 pmid=30877196
# Luis2018 pmid=29255254
# Bule2019 pmid=31645552
# Jin2016 Jin Y, Petricevic M, John A, Raich L, Jenkins H, Portela De Souza L, Cuskin F, Gilbert HJ, Rovira C, Goddard-Borger ED, Williams SJ, and Davies GJ. ''A β-Mannanase with a Lysozyme-like Fold and a Novel Molecular Catalytic Mechanism.'' ACS Cent Sci. 2016 Nov [http://dx.doi.org/10.1021/acscentsci.6b00232 DOI:10.1021/acscentsci.6b00232]
# Yamada2017 pmid=28392148
# Ohnuma2014 pmid=24582745
# Thompson2012 pmid=22219371
# Xie2016 pmid=27777307
# Williams2014 pmid=24339341
# Hehemann_2_2012 pmid=22393053
# Huang2012 pmid=22992047
# Noach2016 pmid=27038508
# Alonso-Gil2016 pmid=28026180
# Huang2014 Huang CH, Zhu Z, Cheng YS, Chan HC, Ko TP, Chen CC, Wang I, Ho MR, Hsu ST, Zeng YF, Huang YN, Liu JR, Guo RT. ''Structure and Catalytic Mechanism of a Glycoside Hydrolase Family-127 β-L-Arabinofuranosidase (HypBA1).'' J Bioprocess Biotech. 2014 4:171 [http://dx.doi.org/10.4172/2155-9821.1000171 DOI:10.4172/2155-9821.1000171]
# Tsuda2015 pmid=26632508
# Barbirz2008 pmid=18547389
# Tanaka2019 pmid=30926603
# Armstrong2020 pmid=31871050
# Santos2020 pmid=32451508
# Kashima2021 pmid=34688653

</biblio>

[[Category:Definitions and explanations]]

Syn/anti lateral protonation

2020-08-09T19:21:18Z

Wim Nerinckx: GH164 is anti

{{CuratorApproved}}
* [[Author]]: ^^^Wim Nerinckx^^^
* [[Responsible Curator]]: ^^^Spencer Williams^^^

----

== Overview ==

This page provides a table that summarizes the spatial positioning of the catalytic [[general acid]] residue in the active sites of [[glycoside hydrolase]]s, relative to the substrate. The table below updates those found in the seminal paper on this concept by Heightman and Vasella <cite>HeightmanVasella1999</cite>, and a following paper by Nerinckx ''et al.'' <cite>Nerinckx2005</cite>.

== Background ==

The ''"not from above, but from the side"'' concept of semi-lateral glycosidic oxygen [[General_acid/base|protonation]] by [[glycoside hydrolase]]s was introduced by Heightman and Vasella <cite>HeightmanVasella1999</cite>. It was originally only described for [[Anomeric centre (alpha and beta)|beta]]-equatorial [[glycoside hydrolase]]s, but appears to be equally applicable to enzymes acting on an [[Anomeric centre (alpha and beta)|alpha]]-axial glycosidic bond <cite>Nerinckx2005</cite>. When dividing [[Sub-site nomenclature|subsite -1]] into half-spaces by a plane defined by the glycosidic oxygen and C1' and H1' of the –1 glycoside, many ligand-complexed structures reveal that the [[General_acid/base|proton donor]] is positioned either in the ''syn'' half-space (near the ring-oxygen of the –1 glycoside), or in the ''anti'' half-space (on the opposite side of the ring-oxygen). Members of the same GH [[Families|family]] appear to share a common ''syn'' or ''anti'' [[General_acid/base|protonator]] arrangement and further, this specificity appears to be preserved within [[Clans|Clans]] of [[Families|families]]. This page's compilation of [[Sub-site nomenclature|subsite -1]] occupied complexes shows that about 70% of all GH [[Families|families]] are ''anti'' [[General_acid/base|protonators]].

Closer inspection of crystal structures of [[Sub-site nomenclature|–1/+1 subsite]]-spanning substrates, or substrate-analogue ligands, in complex with enzymes reveals a further intriguing corollary <cite>Nerinckx2005 Wu2012</cite>. In substrate-bound complexes with ''anti'' [[General_acid/base|protonating]] GH enzymes, the scissile [[Anomeric centre (alpha and beta)|anomeric bond]] (often studied using the thio-analogue) shows a dihedral angle φ (O5'-C1'-[O,S]x-Cx) that is in the lowest-energy synclinal (gauche) conformation. The rationale for this is that a minus synclinal dihedral angle φ for an equatorial glycosidic bond, or plus synclinal for an axial glycosidic bond <cite>Perez1978</cite>, allows for hyperconjugative overlap of the C1'-O5' antibonding orbital with an antiperiplanar-oriented lone pair orbital lobe of the glycosidic oxygen, thereby creating partial double bond character and stabilization of the glycosidic bond by 4–5 kcal/mol; this ground-state stabilizing phenomenon is known as the ‘exo-anomeric effect’ <cite>Cramer1997 Johnson2009 Alonso2016</cite>. ''Anti'' [[General_acid/base|protonation]] occurs on the glycosidic oxygen’s antiperiplanar lone pair, thereby removing the stabilizing exo-anomeric effect. This suggests that ''anti'' [[General_acid/base|protonation]] is an enzymic approach for lowering the activation barrier leading to the [[Transition state|transition state]] (Figure 1 centre).

''Syn'' [[General_acid/base|protonating]] [[glycoside hydrolase]]s apparently make use of a different approach <cite>Nerinckx2005 Wu2012</cite>. In many [[Sub-site nomenclature|–1/+1 subsite]]-spanning ligand complexes, the dihedral angle φ of the scissile anomeric bond has been rotated away from its lowest-energy synclinal position: clockwise to minus-anticlinal or antiperiplanar for beta-equatorial; counterclockwise to plus-anticlinal or antiperiplanar for alpha-axial [[Anomeric centre (alpha and beta)|anomeric bonds]]. This removes the hyperconjugative overlap and thus also the stabilizing exo-anomeric effect. And because of this rotation, a lone pair of the glycosidic oxygen is directed into the ''syn'' half-space, allowing it to be protonated by the ''syn''-positioned [[General_acid/base|proton donor]] (Figure 1 right).

[[File:Syn_anti.jpg|800px|thumb|center|Figure 1. Newman projections, with the glycosidic oxygen as proximal atom and the anomeric carbon as distal atom, showing ''anti'' (centre) versus ''syn'' (right) semi-lateral [[General_acid/base|protonation]] in beta-equatorial (top) and alpha-axial (bottom) [[glycoside hydrolase]]s. The indicated φ is the dihedral angle for O5'-C1'-O4-C4.]]

== Table of ''syn/anti'' protonation examples ==

This table contains only one example per GH [[Families|family]] of a ligand-complexed protein structure where the ''syn'' or ''anti'' positioning of the [[General_acid/base|proton donor]] can be clearly observed; other examples may be available on a [[Families|family-by-family]] basis. The reader is thus advised to consult the [http://www.cazy.org/fam/acc_GH.html#table CAZy database] for a current, comprehensive list of CAZyme structures. Where available, the selected examples are Michaelis-type complexes with the ligand spanning the [[Sub-site nomenclature|-1/+1 subsites]], since these have an intact glycosidic or thioglycosidic bond, or are ''N''-analogs of the substrate (''e.g.'' acarbose). In some examples, the [[General_acid/base|proton donor]] has been mutated (''e.g.'', to the corresponding amide or to an alanine), and in those cases one may wish to look at a superposition of the given PDB example with the structure of the native enzyme. If a Michaelis-type complex is not yet available, the second and third example choices, respectively, are trapped glycosyl-enzyme [[intermediate]]s and product complexes where [[Sub-site nomenclature|subsite -1]] is occupied.

''Please also be aware that this is a large table with many data. Please contact the page Author or Responsible Curator with corrections.''

=== Table ===
This table can be re-sorted by clicking on the icons in the header (''javascript must be turned on in your browser''). To reset the page to be sorted by GH family, click the ''View'' tab at the very top of the page.

{| {{Prettytable}} class="sortable"
|- valign="top"
! '''Family'''
! '''Clan'''
! '''Structure fold '''
! '''Anomeric specificity'''
! '''Mechanism'''
! '''''Syn/anti'' protonator'''
! '''Example PDB ID'''
! '''Enzyme'''
! '''Organism'''
! '''Ligand'''
! '''General acid'''
! '''Nucleophile or General base'''
! '''Reference'''
|-
| [[GH1]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2cer 2cer]
| β-glycosidase S
| ''Sulfolobus solfataricus'' P2
| phenethyl glucoimidazole
| '''Glu206'''
| Glu387
| <cite>Gloster2006</cite>
|-
| [[GH2]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vzu 2vzu]
| exo-β-glucosaminidase
| ''Amicolatopsis orientalis''
| PNP-β-{{Smallcaps|d}}-glucosamine
| '''Glu469'''
| Glu541
| <cite>van_Bueren2009</cite>
|-
| [[GH3]]
| none
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1iex 1iex]
| exo-1,3-1,4-glucanase
| ''Hordeum vulgare''
| thiocellobiose
| '''Glu491'''
| Asp285
| <cite>Hrmova2001</cite>
|-
| [[GH4]]
| none
| Rossmann + α6/β3 + β3/α4
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1u8x 1u8x]
| 6-P-α-glucosidase
| ''Bacillus subtilis''
| alpha-{{Smallcaps|d}}-glucose-6-phosphate
| '''Asp172'''
| Not applicable
| <cite>Rajan2004</cite>
|-

| [[GH5]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1h2j 1h2j]
| endo-β-1,4-glucanase
| ''Bacillus agaradhaerens''
| 2',4'-DNP-2-F-cellobioside
| '''Glu129'''
| Glu228
| <cite>Varrot2003</cite>
|-
| [[GH6]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1qjw 1qjw]
| cellobiohydrolase 2
| ''Hypocrea jecorina''
| (Glc)2-S-(Glc)2
| '''Asp221'''
| debated
| <cite>Zhou1999</cite>
|-
| [[GH7]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1ovw 1ovw]
| endo-1,4-glucanase
| ''Fusarium oxysporum''
| thio-(Glc)5
| '''Glu202'''
| Glu197
| <cite>Sulzenbacher1999</cite>
|-
| [[GH8]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1kwf 1kwf]
| endo-1,4-glucanase
| ''Clostridium thermocellum''
| cellopentaose
| '''Glu95'''
| Asp278
| <cite>Guerin2002</cite>
|-
| [[GH9]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1rq5 1rq5]
| cellobiohydrolase
| ''Clostridium thermocellum''
| cellotetraose
| '''Glu795'''
| Asp383
| <cite>Schubot2004</cite>
|-
| [[GH10]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2d24 2d24]
| β-1,4-xylanase
| ''Streptomyces olivaceoviridis'' E-86
| xylopentaose
| '''Glu128'''
| Glu236
| <cite>Suzuki2009</cite>
|-
| [[GH11]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}4hk8 4hk8]
| endo-β-1,4-xylanase
| ''Hypocrea jecorina''
| xylohexaose
| '''Glu177'''
| Glu86
| <cite>Wan2014</cite>
|-
| [[GH12]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1w2u 1w2u]
| endoglucanase
| ''Humicola grisea''
| thiocellotetraose
| '''Glu205'''
| Glu120
| <cite>Sandgren2004</cite>
|-
| [[GH13]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1cxk 1cxk]
| β-cyclodextrin glucanotransferase
| ''Bacillus circulans''
| maltononaose
| '''Glu257'''
| Asp229
| <cite>Uitdehaag1999</cite>
|-
| [[GH14]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1itc 1itc]
| β-amylase
| ''Bacillus cereus''
| maltopentaose
| '''Glu172'''
| Glu367
| <cite>Miyake2003</cite>
|-
| [[GH15]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1dog 1dog]
| glucoamylase
| ''Aspergillus awamori''
| 1-deoxynojirimycin
| '''Glu179'''
| Glu400
| <cite>Harris1993</cite>
|-
| [[GH16]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1urx 1urx]
| β-agarase A
| ''Zobellia galactanivorans''
| oligoagarose
| '''Glu152'''
| Glu147
| <cite>Allouch2004</cite>
|-
| [[GH17]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzj 4gzj]
| endo-β-1,3-glucanase
| ''Solanum tuberosum''
| laminaratriose + laminarabiose
| '''Glu118'''
| Glu259
| <cite>Wojtkowiak2013</cite>
|-
| [[GH18]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1ffr 1ffr]
| chitinase A
| ''Serratia marcescens''
| (NAG)6
| '''Glu315'''
| internal
| <cite>Papanikolau2001</cite>
|-
| [[GH19]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}3wh1 3wh1]
| chitinase
| ''Bryum coronatum''
| (GlcNAc)4
| '''Glu61'''
| Glu70
| <cite>Ohnuma2014</cite>
|-
| [[GH20]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1c7s 1c7s]
| chitobiase
| ''Serratia marcescens''
| chitobiose
| '''Glu540'''
| internal
| <cite>Prag2000</cite>
|-
| [[GH22]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1h6m 1h6m]
| lysozyme C
| ''Gallus gallus''
| Chit-2-F-chitosyl
| '''Glu35'''
| Asp52
| <cite>Vocadlo2001</cite>
|-
| [[GH23]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1lsp 1lsp]
| lysozyme G
| ''Cygnus atratus''
| Bulgecin A
| '''Glu73'''
| internal
| <cite>Karlsen1996</cite>
|-
| [[GH24]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}148l 148l]
| lysozyme E
| Bacteriophage T4
| chitobiosyl
| '''Glu11'''
| Glu26
| <cite>Baldwin1993</cite>
|-
| [[GH26]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vx6 2vx6]
| exo-β-mannanase
| ''Cellvibrio japonicus'' Ueda107
| Gal1Man4
| '''Glu221'''
| Glu338
| <cite>Cartmell2008</cite>
|-
| [[GH27]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}} / beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3lrm 3lrm]
| α-galactosidase
| ''Saccharomyces cerevisiae''
| raffinose
| '''Asp209'''
| Asp141
| <cite>Fernandez-Leiro2010</cite>
|-
| [[GH28]]
| N
| β-helix
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}2uvf 2uvf]
| exo-polygalacturonosidase
| ''Yersinia enterocolitica'' ATCC9610D
| digalacturonic acid
| '''Asp402'''
| Asp381 Asp403
| <cite>Abbott2007</cite>
|-
| [[GH29]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| '''''syn'''''
| [{{PDBlink}}3uet 3uet]
| α-1,3/4-fucosidase
| ''Bifidobacterium longum'' subsp. infantis
| lacto-''N''-fucopentaose II
| '''Glu217'''
| Asp172
| <cite>Sakurama2012</cite>
|-
| [[GH30]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2y24 2y24]
| glucurono-xylanase
| ''Dickea chrysanthemi'' D1
| glucuronoxylan tetrasaccharide
| '''Glu163'''
| Glu253
| <cite>Urbanikova2011</cite>
|-
| [[GH31]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2qmj 2qmj]
| maltase-glucoamylase
| ''Homo sapiens''
| acarbose
| '''Asp542'''
| Asp443
| <cite>Sim2008</cite>
|-
| [[GH32]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2add 2add]
| fructan β-(2,1)-fructosidase
| ''Cichorium intybus''
| sucrose
| '''Glu201'''
| Asp22
| <cite>Verhaest2007</cite>
|-
| [[GH33]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1s0i 1s0i]
| transsialidase
| ''Trypanosoma cruzi''
| sialyllactose
| '''Asp59'''
| Tyr342
| <cite>Amaya2004</cite>
|-
| [[GH34]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzw 4gzw]
| N2 neuraminidase
| ''Influenza'' A Tanzania/205/2010 H3N2
| α-{{Smallcaps|d}}-Neup5Ac-(2,3)-β-{{Smallcaps|d}}-Galp-(1,4)-β-{{Smallcaps|d}}-GlcpNAc
| '''Asp151'''
| Tyr406
| <cite>Zhu2012</cite>
|-
| [[GH35]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3ogv 3ogv]
| β-galactosidase
| ''Hypocrea jecorina''
| 2-phenylethyl 1-thio-β-{{Smallcaps|d}}-galactopyranoside
| '''Glu200'''
| Glu298
| <cite>Maksimainen2011</cite>
|-
| [[GH36]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4fnu 4fnu]
| β-galactosidase
| ''Geobacillus stearothermophilus''
| stachyose
| '''Asp584'''
| Asp478
| <cite>Merceron2012</cite>
|-
| [[GH37]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2jf4 2jf4]
| trehalase
| ''Escherichia coli''
| validoxylamine
| '''Asp312'''
| Glu496
| <cite>Gibson2007</cite>
|-
| [[GH38]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3czn 3czn]
| Golgi α-mannosidase II
| ''Drosophila melanogaster''
| GlcNAcMan(5)GlcNAc(2)
| '''Asp341'''
| Asp204
| <cite>Shah2008</cite>
|-
| [[GH39]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2bfg 2bfg]
| β-xylosidase
| ''Geobacillus stearothermophilus''
| 2,5-dinitrophenyl-β-{{Smallcaps|d}}-xyloside
| '''Glu160'''
| Glu278
| <cite>Czjzek2005</cite>
|-
| [[GH42]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ucf 4ucf]
| β-galactosidase
| ''Bifidobacterium bifidum''
| {{Smallcaps|d}}-galactose
| '''Glu161'''
| Glu320
| <cite>Godoy2016</cite>
|-
| [[GH43]]
| F
| 5-fold β-propeller
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3akh 3akh]
| exo-1,5-α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces avermitilis''
| α-1,5-arabinofuranotriose
| '''Glu196'''
| Asp220
| <cite>Fujimoto2010</cite>
|-
| [[GH44]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2eqd 2eqd]
| endoglucanase
| ''Clostridium thermocellum''
| cellooctaose
| '''Glu186'''
| Glu359
| <cite>Kitago2007</cite>
|-
| [[GH45]]
| none
| 6-stranded β-barrel
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4eng 4eng]
| endo-1,4-glucanase
| ''Humicola insolens''
| cellohexaose
| '''Asp121'''
| Asp10
| <cite>Davies1996</cite>
|-
| [[GH46]]
| I
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4olt 4olt]
| chitosanase
| ''Microbacterium sp.'' OU01
| hexa-glucosamine
| '''Glu25'''
| Asp43
| <cite>Lyu2014</cite>
|-
| [[GH47]]
| none
| (α/α)7
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1x9d 1x9d]
| α-mannosidase I
| ''Homo sapiens''
| Me-2-S-(α-Man)-2-thio-α-Man
| '''Asp463'''
| Glu599
| <cite>Karaveg2005</cite>, <cite>Nerinckx2008</cite>
|-
| [[GH48]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH8''
|
|
|
|
|
|
|-
| [[GH49]]
| N
| β-helix
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH28''
|
|
|
|
|
|
|-
| [[GH50]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4bq5 4bq5]
| exo-β-agarase
| ''Saccharophagus degradans''
| neoagarotetraose
| '''Glu535'''
| Glu695
| <cite>Pluvinage2013</cite>
|-
| [[GH51]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1qw9 1qw9]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Geobacillus stearothermophilus''
| PNP-{{Smallcaps|l}}-arabinofuranoside
| '''Glu175'''
| Glu294
| <cite>Hoevel2003</cite>
|-
| [[GH52]]
| O
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4c1p 4c1p]
| β-xylosidase
| ''Geobacillus thermoglucosidasius''
| xylobiose
| '''Asp517'''
| Glu537
| <cite>Espina2014</cite>
|-
| [[GH53]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2ccr 2ccr]
| β-1,4-galactanase
| ''Bacillus licheniformis''
| galactotriose
| '''Glu165'''
| Glu263
| <cite>Le_Nours2009</cite>
|-
| [[GH54]]
| none
| β-sandwich
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1wd4 1wd4]
| α-{{Smallcaps|l}}-arabinofuranosidase B
| ''Aspergillus kawachii''
| {{Smallcaps|l}}-arabinofuranose
| '''Asp297'''
| Glu221
| <cite>Miyanaga2004</cite>
|-
| [[GH55]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4tz5 4tz5]
| exo-β-1,3-glucanase
| ''Streptomyces sp.'' SirexAA-E
| laminarihexaose
| '''Glu502'''
| unknown
| <cite>Bianchetti2015</cite>
|-
| [[GH56]]
| none
| (β/α)7
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1fcv 1fcv]
| hyaluronidase
| ''Apis mellifera''
| (hyaluron.)4
| '''Glu113'''
| internal
| <cite>Markovic-Housley2000</cite>
|-
| [[GH57]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1k1y 1k1y]
| glucanotransferase
| ''Thermococcus litoralis''
| acarbose
| '''Asp214'''
| Glu123
| <cite>Imamura2003</cite>
|-
| [[GH59]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ccc 4ccc]
| β-galactocerebrosidase
| ''Mus musculus''
| PNP-β-{{Smallcaps|d}}-galactoside
| '''Glu182'''
| Glu258
| <cite>Hill2013</cite>
|-
| [[GH62]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3wn0 3wn0]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces coelicolor''
| β-{{Smallcaps|l}}-Arabinofuranose
| '''Glu361'''
| Asp202
| <cite>Maehara2014</cite>
|-
| [[GH63]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5ca3 5ca3]
| α-glucosidase
| ''Escherichia coli''
| glucose and lactose
| '''Asp501'''
| Glu727
| <cite>Miyazaki2016</cite>
|-
| [[GH65]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}4ktr 4ktr]
| 2-O-α-glucosylglycerol phosphorylase
| ''Bacillus selenitireducens''
| isofagomine
| '''Glu475'''
| phosphate
| <cite>Touhara2014</cite>
|-
| [[GH66]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5axh 5axh]
| dextranase
| ''Thermoanaerobacter pseudethanolicus''
| isomaltohexaose
| '''Glu374'''
| Asp312
| <cite>Suzuki2016</cite>
|-
| [[GH67]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1l8n 1l8n]
| α-glucuronidase
| ''Geobacillus stearothermophilus''
| 4-O-methyl-{{Smallcaps|d}}-glucuronic acid and xylotriose
| '''Glu286'''
| Asp364 Glu392
| <cite>Golan2004</cite>
|-
| [[GH68]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1pt2 1pt2]
| levansucrase
| ''Bacillus subtilis''
| sucrose
| '''Glu342'''
| Asp86
| <cite>Meng2003</cite>
|-
| [[GH70]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3aic 3aic]
| glucansucrase
| ''Streptococcus mutans''
| α-acarbose
| '''Glu515'''
| Asp477
| <cite>Ito2011</cite>
|-
| [[GH72]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w62 2w62]
| β-1,3-glucanotransferase
| ''Saccharomyces cerevisiae'' S288C
| laminaripentaose
| '''Glu176'''
| Glu275
| <cite>Hurtado-Gerrero2009</cite>
|-
| [[GH74]]
| none
| 7-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}2ebs 2ebs]
| cellobiohydrolase (OXG-RCBH)
| ''Geotrichum sp.'' m128
| xyloglucan heptasaccharide
| '''Asp465'''
| Asp35
| <cite>Yaoi2007</cite>
|-
| [[GH76]]
| none
| (α/α)6
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5agd 5agd]
| endo-α-1,6-mannanase
| ''Bacillus circulans''
| α-1,6-mannopentaose
| '''Asp125'''
| Asp124
| <cite>Thompson2015</cite>
|-
| [[GH77]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2oww 2oww]
| 4-α-glucanotransferase
| ''Thermus thermofilus''
| acarbose + 4-deoxy-α-{{Smallcaps|d}}-glucose
| '''Glu340'''
| Asp293
| <cite>Barends2007</cite>
|-
| [[GH78]]
| H
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3w5n 3w5n]
| α-{{Smallcaps|l}}-rhamnosidase
| ''Streptomyces avermitilis''
| {{Smallcaps|l}}-rhamnose
| '''Glu636'''
| Glu895
| <cite>Fujimoto2013</cite>
|-
| [[GH79]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5e9c 5e9c]
| heparanase
| ''Homo sapiens''
| heparin tetrasaccharide
| '''Glu225'''
| Glu343
| <cite>Wu2015</cite>
|-
| [[GH80]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH24''
|
|
|
|
|
|
|-
| [[GH81]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5t4g 5t4g]
| endo-β-1,3-glucanase
| ''Bacillus halodurans'' C-125
| laminarin
| '''Asp466'''
| Glu542
| <cite>Pluvinage2017</cite>
|-
| [[GH83]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1z4x 1z4x]
| hemagglutinin-neuraminidase
| Simian virus 5
| α-2,3-sialyllactose
| '''Glu247''' relay
| Tyr523
| <cite>Yuan2005</cite>
|-
| [[GH84]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2chn 2chn]
| β-''N''-acetyl-glucosaminidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| NAG-thiazoline
| '''Glu242'''
| internal
| <cite>Dennis2006</cite>
|-
| [[GH85]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w92 2w92]
| endo-β-''N''-acetyl-glucosaminidase D
| ''Streptococcus pneumoniae'' TIGR4
| NAG-thiazoline
| '''Glu337'''
| internal
| <cite>Abbott2009</cite>
|-
| [[GH86]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4aw7 4aw7]
| β-porphyranase
| ''Bacteroides plebeius''
| porphyran fragment
| '''Glu152'''
| Glu279
| <cite>Hehemann_1_2012</cite>
|-
| [[GH89]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vcb 2vcb]
| α-''N''-acetyl-glucosaminidase
| ''Clostridium perfringens''
| PUGNAc
| '''Glu483'''
| Glu601
| <cite>Ficko-Blean2008</cite>
|-
| [[GH92]]
| none
| (α/α)6 and β-sandwich
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ww1 2ww1]
| α-1,2-mannosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| thiomannobioside
| '''Glu533'''
| Asp644 Asp642
| <cite>Zhu2009</cite>
|-
| [[GH93]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3a72 3a72]
| exo-arabinanase
| ''Penicillium chrysogenum''
| arabinobiose
| '''Glu246'''
| Glu174
| <cite>Sogabe2011</cite>
|-
| [[GH94]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4zli 4zli]
| cellobionic acid phosphorylase
| ''Saccharophagus degradans''
| 3-O-β-{{Smallcaps|d}}-glucopyranosyl-α-{{Smallcaps|d}}-glucopyranuronic acid
| '''Asp472'''
| phosphate
| <cite>Nam2015</cite>
|-
| [[GH95]]
| none
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ead 2ead]
| α-1,2-{{Smallcaps|l}}-fucosidase
| ''Bifidobacterium bifidum''
| Fuc-α-1,2-Gal
| '''Glu566'''
| Asn423 Asp766
| <cite>Nagae2007</cite>
|-
| [[GH97]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining + inverting
| '''''anti'''''
| [{{PDBlink}}2zq0 2zq0]
| α-glucosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| acarbose
| '''Glu532'''
| Glu508
| <cite>Kitamura2008</cite>
|-
| [[GH98]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2wmg 2wmg]
| endo-β-1,4-galactosidase
| ''Streptococcus pneumoniae''
| A-LewisY pentasaccharide
| '''Glu158'''
| Asp251 Glu301
| <cite>Higgins2009</cite>
|-
| [[GH99]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ad4 4ad4]
| endo-α-mannosidase
| ''Bacteroides xylanisolvens''
| glucose-1,3-isofagomine and α-1,2- mannobiose
| '''Glu336'''
| debated
| <cite>Thompson2012</cite>
|-
| [[GH100]]
| none
| (α/α)6 core
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5gop 5gop]
| invertase
| ''Anabaena (Nostoc) sp.'' pcc7120
| sucrose
| '''Asp188'''
| Glu414
| <cite>Xie2016</cite>
|-
| [[GH102]]
| none
| double-ψ β-barrel
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}2pi8 2pi8]
| lytic transglycosylase A
| ''Escherichia coli''
| chitohexaose
| '''Asp308'''
| none
| <cite>van_Straaten2007</cite>
|-
| [[GH103]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1d0k 1d0k]
| lytic transglycosylase SLT35
| ''Escherichia coli''
| murodipeptides
| '''Glu162'''
| internal
| <cite>van_Asselt2000</cite>
|-
| [[GH106]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5mwk 5mwk]
| α-{{Smallcaps|l}}-rhamnosidase BT_0986
| ''Bacteroides thetaiotaomicron''
| pectin heptasaccharide
| '''Glu461'''
| Glu593 or Glu561
| <cite>Ndeh2017</cite>
|-
| [[GH107]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| ''predicted syn by clan''
| ''see at GH29''
|
|
|
|
|
|
|-
| [[GH113]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4cd8 4cd8]
| β-mannanase
| ''Alicyclobacillus acidocaldarius''
| mannobioimidazole
| '''Glu151'''
| Glu231
| <cite>Williams2014</cite>
|-
| [[GH116]]
| O
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at GH52''
|
|
|
|
|
|
|-
| [[GH117]]
| none
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}4ak7 4ak7]
| α-1,3-3,6-anhydro-{{Smallcaps|l}}-galactosidase
| ''Bacteroides plebeius''
| neoagarobiose
| '''His302''' (relay from Asp320)
| Asp90
| <cite>Hehemann_2_2012</cite>
|-
| [[GH120]]
| none
| parallel β-helix and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3vsv 3vsv]
| β-xylosidase XylC
| ''Thermoanaerobacterium saccharolyticum'' JW/SL-YS485
| {{Smallcaps|d}}-xylose
| '''Glu405'''
| Asp382
| <cite>Huang2012</cite>
|-
| [[GH123]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5fr0 5fr0]
| exo-β-N-acetyl-galactosaminidase
| ''Clostridium perfringens''
| ''N''-difluoroacetyl-{{Smallcaps|d}}-galactosamine
| '''Glu345'''
| internal
| <cite>Noach2016</cite>
|-
| [[GH125]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5m7y 5m7y]
| exo-α-1,6-mannosidase
| ''Clostridium perfringens''
| 1,6-α-mannotriose
| '''Asp220'''
| Glu393
| <cite>Alonso-Gil2016</cite>
|-
| [[GH127]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3wrg 3wrg]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bifidobacterium longum''
| {{Smallcaps|l}}-arabinose
| '''Glu322'''
| Cys417
| <cite>Huang2014</cite>
|-
| [[GH128]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH1''
|
|
|
|
|
|
|-
| [[GH130]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5b0s 5b0s]
| β-1,2-mannobiose phosphorylase
| ''Listeria innocua''
| β-1,2-mannotriose
| '''Asp141''' relay
| phosphate
| <cite>Tsuda2015</cite>
|-
| [[GH134]]
| none
| β + α
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5jug 5jug]
| β-mannanase
| ''Streptomyces sp.''
| mannopentaose
| '''Glu45'''
| Asp57
| <cite>Jin2016</cite>
|-
| [[GH136]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}5gqf 5gqf]
| lacto-N-biosidase
| ''Bifidobacterium longum''
| lacto-N-biose
| '''Asp411'''
| Asp418
| <cite>Yamada2017</cite>
|-
| [[GH137]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|l}}
| unknown
| '''''anti'''''
| [{{PDBlink}}5mui 5mui]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0996
| ''Bacteroides thetaiotaomicron''
| pectin oligosaccharide
| '''Glu240'''
| Glu159
| <cite>Ndeh2017</cite>

|-
| [[GH138]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}6hzg 6hzg]
| α-1,2-{{Smallcaps|d}}-galacturonidase
| ''Bacteroides paurosaccharolyticus''
| alpha-{{Smallcaps|d}}-galactopyranuronic
| '''Glu294'''
| Glu361
| <cite>Labourel2019</cite>
|-
| [[GH146]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5opj 5opj]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0349
| ''Bacteroides thetaiotaomicron''
| {{Smallcaps|l}}-arabinose
| '''Glu320'''
| Cys416
| <cite>Luis2018</cite>
|-
| [[GH147]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH148]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH149]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH156]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}6s0e 6s0e]
| exo-α-sialidase
| uncultured bacterium pG7
| N-acetyl-2,3-dehydro-2-deoxyneuraminic acid
| '''His134''' (relay from Asp132)
| Asp14
| <cite>Bule2019</cite>

|-
| [[GH157]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-

| [[GH158]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH161]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH162]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}6imw 6imw]
| endo-β-1,2-glucanase
| ''Talaromyces funiculosus''
| beta-1,2-glucan
| '''Glu262''' via C3-OH of glc at subs. +2
| Asp446
| <cite>Tanaka2019</cite>
|-
| [[GH164]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}6t75 6t75]
| β-mannosidase
| ''Bacteroides salyersiae''
| 2-deoxy-2-F-mannosyl
| '''Glu160'''
| Glu297
| <cite>Armstrong2020</cite>

|-
| [http://www.cazy.org/GH0.html n.c.*]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2vjj 2vjj]
| endo-α-N-acetylglucosaminidase
| Bacteriophage HK620
| O18A1 O-antigen hexasaccharide
| '''Asp339'''
| Glu372
| <cite>Barbirz2008</cite>
|}
<nowiki>*</nowiki> n.c.: Found among the collection of [http://www.cazy.org/GH0.html non-classified GH sequences in the CAZy Database].

== References ==

<biblio>
# HeightmanVasella1999 Heightman TD and Vasella AT. ''Recent Insights into Inhibition, Structure, and Mechanism of Configuration-Retaining Glycosidases.'' Angew Chem Int Ed. 1999 38(6):750-770. [http://www3.interscience.wiley.com/journal/55000581/abstract Article online].
# Nerinckx2005 pmid=15642336
# Wu2012 pmid=23137336
# Perez1978 Pérez S and Marchessault RH. ''The exo-anomeric effect: experimental evidence from crystal structures.'' Carbohydr res. 1978 65:114-120. [http://dx.doi.org/10.1016/S0008-6215(00)84218-4 DOI:10.1016/S0008-6215(00)84218-4]
# Cramer1997 Cramer CJ, Truhlar DG, and French AD. ''Exo-anomeric effects on energies and geometries of different conformations of glucose and related systems in the gas phase and aqueous solution.'' Carbohydr res. 1997 298:1-14. [http://dx.doi.org/10.1016/S0008-6215(96)00297-2 DOI:10.1016/S0008-6215(96)00297-2]
# Johnson2009 pmid=19733839
# Alonso2016 pmid=26889578
# Gloster2006 pmid=17002288
# van_Bueren2009 pmid=18976664
# Hrmova2001 pmid=11709165
# Rajan2004 pmid=15341727
# Varrot2003 pmid=12595701
# Zhou1999 pmid=10508787
# Sulzenbacher1999 pmid=10200171
# Urbanikova2011 pmid=21501386
# Guerin2002 pmid=11884144
# Schubot2004 pmid=14756552
# Suzuki2009 pmid=19279191
# Wan2014 pmid=24419374
# Sandgren2004 pmid=15364577
# Uitdehaag1999 pmid=10331869
# Miyake2003 pmid=12741813
# Harris1993 pmid=8431441
# Allouch2004 pmid=15062085
# Wojtkowiak2013 pmid=23275163
# Papanikolau2001 pmid=11560481
# Prag2000 pmid=10884356
# Vocadlo2001 pmid=11518970
# Karlsen1996 pmid=15299731
# Baldwin1993 pmid=8259514
# Cartmell2008 pmid=18799462
# Fernandez-Leiro2010 pmid=20592022
# Abbott2007 pmid=17397864
# Sakurama2012 pmid=22451675
# Sim2008 pmid=18036614
# Verhaest2007 pmid=17335500
# Amaya2004 pmid=15130470
# Zhu2012 pmid=23015718
# Maksimainen2011 pmid=21130883
# Merceron2012 pmid=23012371
# Gibson2007 pmid=17455176
# Shah2008 pmid=18599462
# Czjzek2005 pmid=16212978
# Godoy2016 pmid=27685756
# Fujimoto2010 pmid=20739278
# Kitago2007 pmid=17905739
# Davies1996 pmid=15299721
# Lyu2014 pmid=24766439
# Karaveg2005 pmid=15713668
# Nerinckx2008 pmid=18619586
# Pluvinage2013 pmid=23921382
# Yuan2005 pmid=15893670
# Hoevel2003 pmid=14517232
# Espina2014 pmid=24816105
# Le_Nours2009 pmid=19089956
# Miyanaga2004 pmid=15292273
# Bianchetti2015 pmid=25752603
# Markovic-Housley2000 pmid=11080624
# Imamura2003 pmid=12618437
# Hill2013 pmid=24297913
# Maehara2014 pmid=24482228
# Miyazaki2016 pmid=27688023
# Touhara2014 pmid=24828502
# Suzuki2016 pmid=26494689
# Golan2004 pmid=14573597
# Meng2003 pmid=14517548
# Ito2011 pmid=21354427
# Hurtado-Gerrero2009 pmid=19097997
# Yaoi2007 pmid=17498741
# Thompson2015 pmid=25772148
# Barends2007 pmid=17420245
# Fujimoto2013 pmid=23486481
# Wu2015 pmid=26575439
# Pluvinage2017 pmid=28781080
# Dennis2006 pmid=16565725
# Abbott2009 pmid=19181667
# Hehemann_1_2012 pmid=23150581
# Ficko-Blean2008 pmid=18443291
# Zhu2009 pmid=20081828
# Sogabe2011 pmid=21543843
# Nam2015 pmid=26041776
# Nagae2007 pmid=17459873
# Kitamura2008 pmid=18981178
# Higgins2009 pmid=19608744
# van_Straaten2007 pmid=17502382
# van_Asselt2000 pmid=10684641
# Ndeh2017 pmid=28329766
# Labourel2019 pmid=30877196
# Luis2018 pmid=29255254
# Bule2019 pmid=31645552
# Jin2016 Jin Y, Petricevic M, John A, Raich L, Jenkins H, Portela De Souza L, Cuskin F, Gilbert HJ, Rovira C, Goddard-Borger ED, Williams SJ, and Davies GJ. ''A β-Mannanase with a Lysozyme-like Fold and a Novel Molecular Catalytic Mechanism.'' ACS Cent Sci. 2016 Nov [http://dx.doi.org/10.1021/acscentsci.6b00232 DOI:10.1021/acscentsci.6b00232]
# Yamada2017 pmid=28392148
# Ohnuma2014 pmid=24582745
# Thompson2012 pmid=22219371
# Xie2016 pmid=27777307
# Williams2014 pmid=24339341
# Hehemann_2_2012 pmid=22393053
# Huang2012 pmid=22992047
# Noach2016 pmid=27038508
# Alonso-Gil2016 pmid=28026180
# Huang2014 Huang CH, Zhu Z, Cheng YS, Chan HC, Ko TP, Chen CC, Wang I, Ho MR, Hsu ST, Zeng YF, Huang YN, Liu JR, Guo RT. ''Structure and Catalytic Mechanism of a Glycoside Hydrolase Family-127 β-L-Arabinofuranosidase (HypBA1).'' J Bioprocess Biotech. 2014 4:171 [http://dx.doi.org/10.4172/2155-9821.1000171 DOI:10.4172/2155-9821.1000171]
# Tsuda2015 pmid=26632508
# Barbirz2008 pmid=18547389
# Tanaka2019 pmid=30926603
# Armstrong2020 pmid=31871050

</biblio>

[[Category:Definitions and explanations]]

Syn/anti lateral protonation

2019-12-26T18:02:12Z

Wim Nerinckx: Histidine proton donors of GH117 and GH156 now with their relay helpers resp. Asp320 and Asp132, as explained in this table's ref92 (Hehemann_2_2012).

{{CuratorApproved}}
* [[Author]]: ^^^Wim Nerinckx^^^
* [[Responsible Curator]]: ^^^Spencer Williams^^^

----

== Overview ==

This page provides a table that summarizes the spatial positioning of the catalytic [[general acid]] residue in the active sites of [[glycoside hydrolase]]s, relative to the substrate. The table below updates those found in the seminal paper on this concept by Heightman and Vasella <cite>HeightmanVasella1999</cite>, and a following paper by Nerinckx ''et al.'' <cite>Nerinckx2005</cite>.

== Background ==

The ''"not from above, but from the side"'' concept of semi-lateral glycosidic oxygen [[General_acid/base|protonation]] by [[glycoside hydrolase]]s was introduced by Heightman and Vasella <cite>HeightmanVasella1999</cite>. It was originally only described for [[Anomeric centre (alpha and beta)|beta]]-equatorial [[glycoside hydrolase]]s, but appears to be equally applicable to enzymes acting on an [[Anomeric centre (alpha and beta)|alpha]]-axial glycosidic bond <cite>Nerinckx2005</cite>. When dividing [[Sub-site nomenclature|subsite -1]] into half-spaces by a plane defined by the glycosidic oxygen and C1' and H1' of the –1 glycoside, many ligand-complexed structures reveal that the [[General_acid/base|proton donor]] is positioned either in the ''syn'' half-space (near the ring-oxygen of the –1 glycoside), or in the ''anti'' half-space (on the opposite side of the ring-oxygen). Members of the same GH [[Families|family]] appear to share a common ''syn'' or ''anti'' [[General_acid/base|protonator]] arrangement and further, this specificity appears to be preserved within [[Clans|Clans]] of [[Families|families]]. This page's compilation of [[Sub-site nomenclature|subsite -1]] occupied complexes shows that about 70% of all GH [[Families|families]] are ''anti'' [[General_acid/base|protonators]].

Closer inspection of crystal structures of [[Sub-site nomenclature|–1/+1 subsite]]-spanning substrates, or substrate-analogue ligands, in complex with enzymes reveals a further intriguing corollary <cite>Nerinckx2005 Wu2012</cite>. In substrate-bound complexes with ''anti'' [[General_acid/base|protonating]] GH enzymes, the scissile [[Anomeric centre (alpha and beta)|anomeric bond]] (often studied using the thio-analogue) shows a dihedral angle φ (O5'-C1'-[O,S]x-Cx) that is in the lowest-energy synclinal (gauche) conformation. The rationale for this is that a minus synclinal dihedral angle φ for an equatorial glycosidic bond, or plus synclinal for an axial glycosidic bond <cite>Perez1978</cite>, allows for hyperconjugative overlap of the C1'-O5' antibonding orbital with an antiperiplanar-oriented lone pair orbital lobe of the glycosidic oxygen, thereby creating partial double bond character and stabilization of the glycosidic bond by 4–5 kcal/mol; this ground-state stabilizing phenomenon is known as the ‘exo-anomeric effect’ <cite>Cramer1997 Johnson2009 Alonso2016</cite>. ''Anti'' [[General_acid/base|protonation]] occurs on the glycosidic oxygen’s antiperiplanar lone pair, thereby removing the stabilizing exo-anomeric effect. This suggests that ''anti'' [[General_acid/base|protonation]] is an enzymic approach for lowering the activation barrier leading to the [[Transition state|transition state]] (Figure 1 centre).

''Syn'' [[General_acid/base|protonating]] [[glycoside hydrolase]]s apparently make use of a different approach <cite>Nerinckx2005 Wu2012</cite>. In many [[Sub-site nomenclature|–1/+1 subsite]]-spanning ligand complexes, the dihedral angle φ of the scissile anomeric bond has been rotated away from its lowest-energy synclinal position: clockwise to minus-anticlinal or antiperiplanar for beta-equatorial; counterclockwise to plus-anticlinal or antiperiplanar for alpha-axial [[Anomeric centre (alpha and beta)|anomeric bonds]]. This removes the hyperconjugative overlap and thus also the stabilizing exo-anomeric effect. And because of this rotation, a lone pair of the glycosidic oxygen is directed into the ''syn'' half-space, allowing it to be protonated by the ''syn''-positioned [[General_acid/base|proton donor]] (Figure 1 right).

[[File:Syn_anti.jpg|800px|thumb|center|Figure 1. Newman projections, with the glycosidic oxygen as proximal atom and the anomeric carbon as distal atom, showing ''anti'' (centre) versus ''syn'' (right) semi-lateral [[General_acid/base|protonation]] in beta-equatorial (top) and alpha-axial (bottom) [[glycoside hydrolase]]s. The indicated φ is the dihedral angle for O5'-C1'-O4-C4.]]

== Table of ''syn/anti'' protonation examples ==

This table contains only one example per GH [[Families|family]] of a ligand-complexed protein structure where the ''syn'' or ''anti'' positioning of the [[General_acid/base|proton donor]] can be clearly observed; other examples may be available on a [[Families|family-by-family]] basis. The reader is thus advised to consult the [http://www.cazy.org/fam/acc_GH.html#table CAZy database] for a current, comprehensive list of CAZyme structures. Where available, the selected examples are Michaelis-type complexes with the ligand spanning the [[Sub-site nomenclature|-1/+1 subsites]], since these have an intact glycosidic or thioglycosidic bond, or are ''N''-analogs of the substrate (''e.g.'' acarbose). In some examples, the [[General_acid/base|proton donor]] has been mutated (''e.g.'', to the corresponding amide or to an alanine), and in those cases one may wish to look at a superposition of the given PDB example with the structure of the native enzyme. If a Michaelis-type complex is not yet available, the second and third example choices, respectively, are trapped glycosyl-enzyme [[intermediate]]s and product complexes where [[Sub-site nomenclature|subsite -1]] is occupied.

''Please also be aware that this is a large table with many data. Please contact the page Author or Responsible Curator with corrections.''

=== Table ===
This table can be re-sorted by clicking on the icons in the header (''javascript must be turned on in your browser''). To reset the page to be sorted by GH family, click the ''View'' tab at the very top of the page.

{| {{Prettytable}} class="sortable"
|- valign="top"
! '''Family'''
! '''Clan'''
! '''Structure fold '''
! '''Anomeric specificity'''
! '''Mechanism'''
! '''''Syn/anti'' protonator'''
! '''Example PDB ID'''
! '''Enzyme'''
! '''Organism'''
! '''Ligand'''
! '''General acid'''
! '''Nucleophile or General base'''
! '''Reference'''
|-
| [[GH1]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2cer 2cer]
| β-glycosidase S
| ''Sulfolobus solfataricus'' P2
| phenethyl glucoimidazole
| '''Glu206'''
| Glu387
| <cite>Gloster2006</cite>
|-
| [[GH2]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vzu 2vzu]
| exo-β-glucosaminidase
| ''Amicolatopsis orientalis''
| PNP-β-{{Smallcaps|d}}-glucosamine
| '''Glu469'''
| Glu541
| <cite>van_Bueren2009</cite>
|-
| [[GH3]]
| none
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1iex 1iex]
| exo-1,3-1,4-glucanase
| ''Hordeum vulgare''
| thiocellobiose
| '''Glu491'''
| Asp285
| <cite>Hrmova2001</cite>
|-
| [[GH4]]
| none
| Rossmann + α6/β3 + β3/α4
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1u8x 1u8x]
| 6-P-α-glucosidase
| ''Bacillus subtilis''
| alpha-{{Smallcaps|d}}-glucose-6-phosphate
| '''Asp172'''
| Not applicable
| <cite>Rajan2004</cite>
|-

| [[GH5]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1h2j 1h2j]
| endo-β-1,4-glucanase
| ''Bacillus agaradhaerens''
| 2',4'-DNP-2-F-cellobioside
| '''Glu129'''
| Glu228
| <cite>Varrot2003</cite>
|-
| [[GH6]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1qjw 1qjw]
| cellobiohydrolase 2
| ''Hypocrea jecorina''
| (Glc)2-S-(Glc)2
| '''Asp221'''
| debated
| <cite>Zhou1999</cite>
|-
| [[GH7]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1ovw 1ovw]
| endo-1,4-glucanase
| ''Fusarium oxysporum''
| thio-(Glc)5
| '''Glu202'''
| Glu197
| <cite>Sulzenbacher1999</cite>
|-
| [[GH8]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1kwf 1kwf]
| endo-1,4-glucanase
| ''Clostridium thermocellum''
| cellopentaose
| '''Glu95'''
| Asp278
| <cite>Guerin2002</cite>
|-
| [[GH9]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1rq5 1rq5]
| cellobiohydrolase
| ''Clostridium thermocellum''
| cellotetraose
| '''Glu795'''
| Asp383
| <cite>Schubot2004</cite>
|-
| [[GH10]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2d24 2d24]
| β-1,4-xylanase
| ''Streptomyces olivaceoviridis'' E-86
| xylopentaose
| '''Glu128'''
| Glu236
| <cite>Suzuki2009</cite>
|-
| [[GH11]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}4hk8 4hk8]
| endo-β-1,4-xylanase
| ''Hypocrea jecorina''
| xylohexaose
| '''Glu177'''
| Glu86
| <cite>Wan2014</cite>
|-
| [[GH12]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1w2u 1w2u]
| endoglucanase
| ''Humicola grisea''
| thiocellotetraose
| '''Glu205'''
| Glu120
| <cite>Sandgren2004</cite>
|-
| [[GH13]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1cxk 1cxk]
| β-cyclodextrin glucanotransferase
| ''Bacillus circulans''
| maltononaose
| '''Glu257'''
| Asp229
| <cite>Uitdehaag1999</cite>
|-
| [[GH14]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1itc 1itc]
| β-amylase
| ''Bacillus cereus''
| maltopentaose
| '''Glu172'''
| Glu367
| <cite>Miyake2003</cite>
|-
| [[GH15]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1dog 1dog]
| glucoamylase
| ''Aspergillus awamori''
| 1-deoxynojirimycin
| '''Glu179'''
| Glu400
| <cite>Harris1993</cite>
|-
| [[GH16]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1urx 1urx]
| β-agarase A
| ''Zobellia galactanivorans''
| oligoagarose
| '''Glu152'''
| Glu147
| <cite>Allouch2004</cite>
|-
| [[GH17]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzj 4gzj]
| endo-β-1,3-glucanase
| ''Solanum tuberosum''
| laminaratriose + laminarabiose
| '''Glu118'''
| Glu259
| <cite>Wojtkowiak2013</cite>
|-
| [[GH18]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1ffr 1ffr]
| chitinase A
| ''Serratia marcescens''
| (NAG)6
| '''Glu315'''
| internal
| <cite>Papanikolau2001</cite>
|-
| [[GH19]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}3wh1 3wh1]
| chitinase
| ''Bryum coronatum''
| (GlcNAc)4
| '''Glu61'''
| Glu70
| <cite>Ohnuma2014</cite>
|-
| [[GH20]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1c7s 1c7s]
| chitobiase
| ''Serratia marcescens''
| chitobiose
| '''Glu540'''
| internal
| <cite>Prag2000</cite>
|-
| [[GH22]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1h6m 1h6m]
| lysozyme C
| ''Gallus gallus''
| Chit-2-F-chitosyl
| '''Glu35'''
| Asp52
| <cite>Vocadlo2001</cite>
|-
| [[GH23]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1lsp 1lsp]
| lysozyme G
| ''Cygnus atratus''
| Bulgecin A
| '''Glu73'''
| internal
| <cite>Karlsen1996</cite>
|-
| [[GH24]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}148l 148l]
| lysozyme E
| Bacteriophage T4
| chitobiosyl
| '''Glu11'''
| Glu26
| <cite>Baldwin1993</cite>
|-
| [[GH26]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vx6 2vx6]
| exo-β-mannanase
| ''Cellvibrio japonicus'' Ueda107
| Gal1Man4
| '''Glu221'''
| Glu338
| <cite>Cartmell2008</cite>
|-
| [[GH27]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}} / beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3lrm 3lrm]
| α-galactosidase
| ''Saccharomyces cerevisiae''
| raffinose
| '''Asp209'''
| Asp141
| <cite>Fernandez-Leiro2010</cite>
|-
| [[GH28]]
| N
| β-helix
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}2uvf 2uvf]
| exo-polygalacturonosidase
| ''Yersinia enterocolitica'' ATCC9610D
| digalacturonic acid
| '''Asp402'''
| Asp381 Asp403
| <cite>Abbott2007</cite>
|-
| [[GH29]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| '''''syn'''''
| [{{PDBlink}}3uet 3uet]
| α-1,3/4-fucosidase
| ''Bifidobacterium longum'' subsp. infantis
| lacto-''N''-fucopentaose II
| '''Glu217'''
| Asp172
| <cite>Sakurama2012</cite>
|-
| [[GH30]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2y24 2y24]
| glucurono-xylanase
| ''Dickea chrysanthemi'' D1
| glucuronoxylan tetrasaccharide
| '''Glu163'''
| Glu253
| <cite>Urbanikova2011</cite>
|-
| [[GH31]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2qmj 2qmj]
| maltase-glucoamylase
| ''Homo sapiens''
| acarbose
| '''Asp542'''
| Asp443
| <cite>Sim2008</cite>
|-
| [[GH32]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2add 2add]
| fructan β-(2,1)-fructosidase
| ''Cichorium intybus''
| sucrose
| '''Glu201'''
| Asp22
| <cite>Verhaest2007</cite>
|-
| [[GH33]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1s0i 1s0i]
| transsialidase
| ''Trypanosoma cruzi''
| sialyllactose
| '''Asp59'''
| Tyr342
| <cite>Amaya2004</cite>
|-
| [[GH34]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzw 4gzw]
| N2 neuraminidase
| ''Influenza'' A Tanzania/205/2010 H3N2
| α-{{Smallcaps|d}}-Neup5Ac-(2,3)-β-{{Smallcaps|d}}-Galp-(1,4)-β-{{Smallcaps|d}}-GlcpNAc
| '''Asp151'''
| Tyr406
| <cite>Zhu2012</cite>
|-
| [[GH35]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3ogv 3ogv]
| β-galactosidase
| ''Hypocrea jecorina''
| 2-phenylethyl 1-thio-β-{{Smallcaps|d}}-galactopyranoside
| '''Glu200'''
| Glu298
| <cite>Maksimainen2011</cite>
|-
| [[GH36]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4fnu 4fnu]
| β-galactosidase
| ''Geobacillus stearothermophilus''
| stachyose
| '''Asp584'''
| Asp478
| <cite>Merceron2012</cite>
|-
| [[GH37]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2jf4 2jf4]
| trehalase
| ''Escherichia coli''
| validoxylamine
| '''Asp312'''
| Glu496
| <cite>Gibson2007</cite>
|-
| [[GH38]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3czn 3czn]
| Golgi α-mannosidase II
| ''Drosophila melanogaster''
| GlcNAcMan(5)GlcNAc(2)
| '''Asp341'''
| Asp204
| <cite>Shah2008</cite>
|-
| [[GH39]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2bfg 2bfg]
| β-xylosidase
| ''Geobacillus stearothermophilus''
| 2,5-dinitrophenyl-β-{{Smallcaps|d}}-xyloside
| '''Glu160'''
| Glu278
| <cite>Czjzek2005</cite>
|-
| [[GH42]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ucf 4ucf]
| β-galactosidase
| ''Bifidobacterium bifidum''
| {{Smallcaps|d}}-galactose
| '''Glu161'''
| Glu320
| <cite>Godoy2016</cite>
|-
| [[GH43]]
| F
| 5-fold β-propeller
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3akh 3akh]
| exo-1,5-α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces avermitilis''
| α-1,5-arabinofuranotriose
| '''Glu196'''
| Asp220
| <cite>Fujimoto2010</cite>
|-
| [[GH44]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2eqd 2eqd]
| endoglucanase
| ''Clostridium thermocellum''
| cellooctaose
| '''Glu186'''
| Glu359
| <cite>Kitago2007</cite>
|-
| [[GH45]]
| none
| 6-stranded β-barrel
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4eng 4eng]
| endo-1,4-glucanase
| ''Humicola insolens''
| cellohexaose
| '''Asp121'''
| Asp10
| <cite>Davies1996</cite>
|-
| [[GH46]]
| I
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4olt 4olt]
| chitosanase
| ''Microbacterium sp.'' OU01
| hexa-glucosamine
| '''Glu25'''
| Asp43
| <cite>Lyu2014</cite>
|-
| [[GH47]]
| none
| (α/α)7
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1x9d 1x9d]
| α-mannosidase I
| ''Homo sapiens''
| Me-2-S-(α-Man)-2-thio-α-Man
| '''Asp463'''
| Glu599
| <cite>Karaveg2005</cite>, <cite>Nerinckx2008</cite>
|-
| [[GH48]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH8''
|
|
|
|
|
|
|-
| [[GH49]]
| N
| β-helix
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH28''
|
|
|
|
|
|
|-
| [[GH50]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4bq5 4bq5]
| exo-β-agarase
| ''Saccharophagus degradans''
| neoagarotetraose
| '''Glu535'''
| Glu695
| <cite>Pluvinage2013</cite>
|-
| [[GH51]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1qw9 1qw9]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Geobacillus stearothermophilus''
| PNP-{{Smallcaps|l}}-arabinofuranoside
| '''Glu175'''
| Glu294
| <cite>Hoevel2003</cite>
|-
| [[GH52]]
| O
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4c1p 4c1p]
| β-xylosidase
| ''Geobacillus thermoglucosidasius''
| xylobiose
| '''Asp517'''
| Glu537
| <cite>Espina2014</cite>
|-
| [[GH53]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2ccr 2ccr]
| β-1,4-galactanase
| ''Bacillus licheniformis''
| galactotriose
| '''Glu165'''
| Glu263
| <cite>Le_Nours2009</cite>
|-
| [[GH54]]
| none
| β-sandwich
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1wd4 1wd4]
| α-{{Smallcaps|l}}-arabinofuranosidase B
| ''Aspergillus kawachii''
| {{Smallcaps|l}}-arabinofuranose
| '''Asp297'''
| Glu221
| <cite>Miyanaga2004</cite>
|-
| [[GH55]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4tz5 4tz5]
| exo-β-1,3-glucanase
| ''Streptomyces sp.'' SirexAA-E
| laminarihexaose
| '''Glu502'''
| unknown
| <cite>Bianchetti2015</cite>
|-
| [[GH56]]
| none
| (β/α)7
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1fcv 1fcv]
| hyaluronidase
| ''Apis mellifera''
| (hyaluron.)4
| '''Glu113'''
| internal
| <cite>Markovic-Housley2000</cite>
|-
| [[GH57]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1k1y 1k1y]
| glucanotransferase
| ''Thermococcus litoralis''
| acarbose
| '''Asp214'''
| Glu123
| <cite>Imamura2003</cite>
|-
| [[GH59]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ccc 4ccc]
| β-galactocerebrosidase
| ''Mus musculus''
| PNP-β-{{Smallcaps|d}}-galactoside
| '''Glu182'''
| Glu258
| <cite>Hill2013</cite>
|-
| [[GH62]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3wn0 3wn0]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces coelicolor''
| β-{{Smallcaps|l}}-Arabinofuranose
| '''Glu361'''
| Asp202
| <cite>Maehara2014</cite>
|-
| [[GH63]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5ca3 5ca3]
| α-glucosidase
| ''Escherichia coli''
| glucose and lactose
| '''Asp501'''
| Glu727
| <cite>Miyazaki2016</cite>
|-
| [[GH65]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}4ktr 4ktr]
| 2-O-α-glucosylglycerol phosphorylase
| ''Bacillus selenitireducens''
| isofagomine
| '''Glu475'''
| phosphate
| <cite>Touhara2014</cite>
|-
| [[GH66]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5axh 5axh]
| dextranase
| ''Thermoanaerobacter pseudethanolicus''
| isomaltohexaose
| '''Glu374'''
| Asp312
| <cite>Suzuki2016</cite>
|-
| [[GH67]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1l8n 1l8n]
| α-glucuronidase
| ''Geobacillus stearothermophilus''
| 4-O-methyl-{{Smallcaps|d}}-glucuronic acid and xylotriose
| '''Glu286'''
| Asp364 Glu392
| <cite>Golan2004</cite>
|-
| [[GH68]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1pt2 1pt2]
| levansucrase
| ''Bacillus subtilis''
| sucrose
| '''Glu342'''
| Asp86
| <cite>Meng2003</cite>
|-
| [[GH70]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3aic 3aic]
| glucansucrase
| ''Streptococcus mutans''
| α-acarbose
| '''Glu515'''
| Asp477
| <cite>Ito2011</cite>
|-
| [[GH72]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w62 2w62]
| β-1,3-glucanotransferase
| ''Saccharomyces cerevisiae'' S288C
| laminaripentaose
| '''Glu176'''
| Glu275
| <cite>Hurtado-Gerrero2009</cite>
|-
| [[GH74]]
| none
| 7-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}2ebs 2ebs]
| cellobiohydrolase (OXG-RCBH)
| ''Geotrichum sp.'' m128
| xyloglucan heptasaccharide
| '''Asp465'''
| Asp35
| <cite>Yaoi2007</cite>
|-
| [[GH76]]
| none
| (α/α)6
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5agd 5agd]
| endo-α-1,6-mannanase
| ''Bacillus circulans''
| α-1,6-mannopentaose
| '''Asp125'''
| Asp124
| <cite>Thompson2015</cite>
|-
| [[GH77]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2oww 2oww]
| 4-α-glucanotransferase
| ''Thermus thermofilus''
| acarbose + 4-deoxy-α-{{Smallcaps|d}}-glucose
| '''Glu340'''
| Asp293
| <cite>Barends2007</cite>
|-
| [[GH78]]
| H
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3w5n 3w5n]
| α-{{Smallcaps|l}}-rhamnosidase
| ''Streptomyces avermitilis''
| {{Smallcaps|l}}-rhamnose
| '''Glu636'''
| Glu895
| <cite>Fujimoto2013</cite>
|-
| [[GH79]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5e9c 5e9c]
| heparanase
| ''Homo sapiens''
| heparin tetrasaccharide
| '''Glu225'''
| Glu343
| <cite>Wu2015</cite>
|-
| [[GH80]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH24''
|
|
|
|
|
|
|-
| [[GH81]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5t4g 5t4g]
| endo-β-1,3-glucanase
| ''Bacillus halodurans'' C-125
| laminarin
| '''Asp466'''
| Glu542
| <cite>Pluvinage2017</cite>
|-
| [[GH83]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1z4x 1z4x]
| hemagglutinin-neuraminidase
| Simian virus 5
| α-2,3-sialyllactose
| '''Glu247''' relay
| Tyr523
| <cite>Yuan2005</cite>
|-
| [[GH84]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2chn 2chn]
| β-''N''-acetyl-glucosaminidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| NAG-thiazoline
| '''Glu242'''
| internal
| <cite>Dennis2006</cite>
|-
| [[GH85]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w92 2w92]
| endo-β-''N''-acetyl-glucosaminidase D
| ''Streptococcus pneumoniae'' TIGR4
| NAG-thiazoline
| '''Glu337'''
| internal
| <cite>Abbott2009</cite>
|-
| [[GH86]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4aw7 4aw7]
| β-porphyranase
| ''Bacteroides plebeius''
| porphyran fragment
| '''Glu152'''
| Glu279
| <cite>Hehemann_1_2012</cite>
|-
| [[GH89]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vcb 2vcb]
| α-''N''-acetyl-glucosaminidase
| ''Clostridium perfringens''
| PUGNAc
| '''Glu483'''
| Glu601
| <cite>Ficko-Blean2008</cite>
|-
| [[GH92]]
| none
| (α/α)6 and β-sandwich
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ww1 2ww1]
| α-1,2-mannosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| thiomannobioside
| '''Glu533'''
| Asp644 Asp642
| <cite>Zhu2009</cite>
|-
| [[GH93]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3a72 3a72]
| exo-arabinanase
| ''Penicillium chrysogenum''
| arabinobiose
| '''Glu246'''
| Glu174
| <cite>Sogabe2011</cite>
|-
| [[GH94]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4zli 4zli]
| cellobionic acid phosphorylase
| ''Saccharophagus degradans''
| 3-O-β-{{Smallcaps|d}}-glucopyranosyl-α-{{Smallcaps|d}}-glucopyranuronic acid
| '''Asp472'''
| phosphate
| <cite>Nam2015</cite>
|-
| [[GH95]]
| none
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ead 2ead]
| α-1,2-{{Smallcaps|l}}-fucosidase
| ''Bifidobacterium bifidum''
| Fuc-α-1,2-Gal
| '''Glu566'''
| Asn423 Asp766
| <cite>Nagae2007</cite>
|-
| [[GH97]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining + inverting
| '''''anti'''''
| [{{PDBlink}}2zq0 2zq0]
| α-glucosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| acarbose
| '''Glu532'''
| Glu508
| <cite>Kitamura2008</cite>
|-
| [[GH98]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2wmg 2wmg]
| endo-β-1,4-galactosidase
| ''Streptococcus pneumoniae''
| A-LewisY pentasaccharide
| '''Glu158'''
| Asp251 Glu301
| <cite>Higgins2009</cite>
|-
| [[GH99]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ad4 4ad4]
| endo-α-mannosidase
| ''Bacteroides xylanisolvens''
| glucose-1,3-isofagomine and α-1,2- mannobiose
| '''Glu336'''
| debated
| <cite>Thompson2012</cite>
|-
| [[GH100]]
| none
| (α/α)6 core
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5gop 5gop]
| invertase
| ''Anabaena (Nostoc) sp.'' pcc7120
| sucrose
| '''Asp188'''
| Glu414
| <cite>Xie2016</cite>
|-
| [[GH102]]
| none
| double-ψ β-barrel
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}2pi8 2pi8]
| lytic transglycosylase A
| ''Escherichia coli''
| chitohexaose
| '''Asp308'''
| none
| <cite>van_Straaten2007</cite>
|-
| [[GH103]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1d0k 1d0k]
| lytic transglycosylase SLT35
| ''Escherichia coli''
| murodipeptides
| '''Glu162'''
| internal
| <cite>van_Asselt2000</cite>
|-
| [[GH106]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5mwk 5mwk]
| α-{{Smallcaps|l}}-rhamnosidase BT_0986
| ''Bacteroides thetaiotaomicron''
| pectin heptasaccharide
| '''Glu461'''
| Glu593 or Glu561
| <cite>Ndeh2017</cite>
|-
| [[GH107]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| ''predicted syn by clan''
| ''see at GH29''
|
|
|
|
|
|
|-
| [[GH113]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4cd8 4cd8]
| β-mannanase
| ''Alicyclobacillus acidocaldarius''
| mannobioimidazole
| '''Glu151'''
| Glu231
| <cite>Williams2014</cite>
|-
| [[GH116]]
| O
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at GH52''
|
|
|
|
|
|
|-
| [[GH117]]
| none
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}4ak7 4ak7]
| α-1,3-3,6-anhydro-{{Smallcaps|l}}-galactosidase
| ''Bacteroides plebeius''
| neoagarobiose
| '''His302''' (relay from Asp320)
| Asp90
| <cite>Hehemann_2_2012</cite>
|-
| [[GH120]]
| none
| parallel β-helix and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3vsv 3vsv]
| β-xylosidase XylC
| ''Thermoanaerobacterium saccharolyticum'' JW/SL-YS485
| {{Smallcaps|d}}-xylose
| '''Glu405'''
| Asp382
| <cite>Huang2012</cite>
|-
| [[GH123]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5fr0 5fr0]
| exo-β-N-acetyl-galactosaminidase
| ''Clostridium perfringens''
| ''N''-difluoroacetyl-{{Smallcaps|d}}-galactosamine
| '''Glu345'''
| internal
| <cite>Noach2016</cite>
|-
| [[GH125]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5m7y 5m7y]
| exo-α-1,6-mannosidase
| ''Clostridium perfringens''
| 1,6-α-mannotriose
| '''Asp220'''
| Glu393
| <cite>Alonso-Gil2016</cite>
|-
| [[GH127]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3wrg 3wrg]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bifidobacterium longum''
| {{Smallcaps|l}}-arabinose
| '''Glu322'''
| Cys417
| <cite>Huang2014</cite>
|-
| [[GH128]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH1''
|
|
|
|
|
|
|-
| [[GH130]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5b0s 5b0s]
| β-1,2-mannobiose phosphorylase
| ''Listeria innocua''
| β-1,2-mannotriose
| '''Asp141''' relay
| phosphate
| <cite>Tsuda2015</cite>
|-
| [[GH134]]
| none
| β + α
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5jug 5jug]
| β-mannanase
| ''Streptomyces sp.''
| mannopentaose
| '''Glu45'''
| Asp57
| <cite>Jin2016</cite>
|-
| [[GH136]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}5gqf 5gqf]
| lacto-N-biosidase
| ''Bifidobacterium longum''
| lacto-N-biose
| '''Asp411'''
| Asp418
| <cite>Yamada2017</cite>
|-
| [[GH137]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|l}}
| unknown
| '''''anti'''''
| [{{PDBlink}}5mui 5mui]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0996
| ''Bacteroides thetaiotaomicron''
| pectin oligosaccharide
| '''Glu240'''
| Glu159
| <cite>Ndeh2017</cite>

|-
| [[GH138]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}6hzg 6hzg]
| α-1,2-{{Smallcaps|d}}-galacturonidase
| ''Bacteroides paurosaccharolyticus''
| alpha-{{Smallcaps|d}}-galactopyranuronic
| '''Glu294'''
| Glu361
| <cite>Labourel2019</cite>
|-
| [[GH146]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5opj 5opj]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0349
| ''Bacteroides thetaiotaomicron''
| {{Smallcaps|l}}-arabinose
| '''Glu320'''
| Cys416
| <cite>Luis2018</cite>
|-
| [[GH147]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH148]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH149]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH156]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}6s0e 6s0e]
| exo-α-sialidase
| uncultured bacterium pG7
| N-acetyl-2,3-dehydro-2-deoxyneuraminic acid
| '''His134''' (relay from Asp132)
| Asp14
| <cite>Bule2019</cite>

|-
| [[GH157]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-

| [[GH158]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH161]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH162]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}6imw 6imw]
| endo-β-1,2-glucanase
| ''Talaromyces funiculosus''
| beta-1,2-glucan
| '''Glu262''' via C3-OH of glc at subs. +2
| Asp446
| <cite>Tanaka2019</cite>
|-
| [http://www.cazy.org/GH0.html n.c.*]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2vjj 2vjj]
| endo-α-N-acetylglucosaminidase
| Bacteriophage HK620
| O18A1 O-antigen hexasaccharide
| '''Asp339'''
| Glu372
| <cite>Barbirz2008</cite>
|}
<nowiki>*</nowiki> n.c.: Found among the collection of [http://www.cazy.org/GH0.html non-classified GH sequences in the CAZy Database].

== References ==

<biblio>
# HeightmanVasella1999 Heightman TD and Vasella AT. ''Recent Insights into Inhibition, Structure, and Mechanism of Configuration-Retaining Glycosidases.'' Angew Chem Int Ed. 1999 38(6):750-770. [http://www3.interscience.wiley.com/journal/55000581/abstract Article online].
# Nerinckx2005 pmid=15642336
# Wu2012 pmid=23137336
# Perez1978 Pérez S and Marchessault RH. ''The exo-anomeric effect: experimental evidence from crystal structures.'' Carbohydr res. 1978 65:114-120. [http://dx.doi.org/10.1016/S0008-6215(00)84218-4 DOI:10.1016/S0008-6215(00)84218-4]
# Cramer1997 Cramer CJ, Truhlar DG, and French AD. ''Exo-anomeric effects on energies and geometries of different conformations of glucose and related systems in the gas phase and aqueous solution.'' Carbohydr res. 1997 298:1-14. [http://dx.doi.org/10.1016/S0008-6215(96)00297-2 DOI:10.1016/S0008-6215(96)00297-2]
# Johnson2009 pmid=19733839
# Alonso2016 pmid=26889578
# Gloster2006 pmid=17002288
# van_Bueren2009 pmid=18976664
# Hrmova2001 pmid=11709165

# Rajan2004 pmid=15341727
# Varrot2003 pmid=12595701
# Zhou1999 pmid=10508787
# Sulzenbacher1999 pmid=10200171
# Urbanikova2011 pmid=21501386
# Guerin2002 pmid=11884144
# Schubot2004 pmid=14756552
# Suzuki2009 pmid=19279191
# Wan2014 pmid=24419374
# Sandgren2004 pmid=15364577
# Uitdehaag1999 pmid=10331869
# Miyake2003 pmid=12741813
# Harris1993 pmid=8431441
# Allouch2004 pmid=15062085
# Wojtkowiak2013 pmid=23275163
# Papanikolau2001 pmid=11560481
# Prag2000 pmid=10884356
# Vocadlo2001 pmid=11518970
# Karlsen1996 pmid=15299731
# Baldwin1993 pmid=8259514
# Cartmell2008 pmid=18799462
# Fernandez-Leiro2010 pmid=20592022
# Abbott2007 pmid=17397864
# Sakurama2012 pmid=22451675
# Sim2008 pmid=18036614
# Verhaest2007 pmid=17335500
# Amaya2004 pmid=15130470
# Zhu2012 pmid=23015718
# Maksimainen2011 pmid=21130883
# Merceron2012 pmid=23012371
# Gibson2007 pmid=17455176
# Shah2008 pmid=18599462
# Czjzek2005 pmid=16212978
# Godoy2016 pmid=27685756
# Fujimoto2010 pmid=20739278
# Kitago2007 pmid=17905739
# Davies1996 pmid=15299721
# Lyu2014 pmid=24766439
# Karaveg2005 pmid=15713668
# Nerinckx2008 pmid=18619586
# Pluvinage2013 pmid=23921382

# Yuan2005 pmid=15893670
# Hoevel2003 pmid=14517232
# Espina2014 pmid=24816105
# Le_Nours2009 pmid=19089956
# Miyanaga2004 pmid=15292273
# Bianchetti2015 pmid=25752603
# Markovic-Housley2000 pmid=11080624
# Imamura2003 pmid=12618437
# Hill2013 pmid=24297913

# Maehara2014 pmid=24482228

# Miyazaki2016 pmid=27688023
# Touhara2014 pmid=24828502
# Suzuki2016 pmid=26494689
# Golan2004 pmid=14573597
# Meng2003 pmid=14517548
# Ito2011 pmid=21354427
# Hurtado-Gerrero2009 pmid=19097997
# Yaoi2007 pmid=17498741
# Thompson2015 pmid=25772148
# Barends2007 pmid=17420245
# Fujimoto2013 pmid=23486481
# Wu2015 pmid=26575439
# Pluvinage2017 pmid=28781080
# Dennis2006 pmid=16565725
# Abbott2009 pmid=19181667
# Hehemann_1_2012 pmid=23150581
# Ficko-Blean2008 pmid=18443291
# Zhu2009 pmid=20081828
# Sogabe2011 pmid=21543843
# Nam2015 pmid=26041776
# Nagae2007 pmid=17459873
# Kitamura2008 pmid=18981178
# Higgins2009 pmid=19608744
# van_Straaten2007 pmid=17502382
# van_Asselt2000 pmid=10684641
# Ndeh2017 pmid=28329766
# Labourel2019 pmid=30877196
# Luis2018 pmid=29255254

# Bule2019 pmid=31645552

# Jin2016 Jin Y, Petricevic M, John A, Raich L, Jenkins H, Portela De Souza L, Cuskin F, Gilbert HJ, Rovira C, Goddard-Borger ED, Williams SJ, and Davies GJ. ''A β-Mannanase with a Lysozyme-like Fold and a Novel Molecular Catalytic Mechanism.'' ACS Cent Sci. 2016 Nov [http://dx.doi.org/10.1021/acscentsci.6b00232 DOI:10.1021/acscentsci.6b00232]
# Yamada2017 pmid=28392148
# Ohnuma2014 pmid=24582745
# Thompson2012 pmid=22219371
# Xie2016 pmid=27777307
# Williams2014 pmid=24339341
# Hehemann_2_2012 pmid=22393053
# Huang2012 pmid=22992047
# Noach2016 pmid=27038508
# Alonso-Gil2016 pmid=28026180
# Huang2014 Huang CH, Zhu Z, Cheng YS, Chan HC, Ko TP, Chen CC, Wang I, Ho MR, Hsu ST, Zeng YF, Huang YN, Liu JR, Guo RT. ''Structure and Catalytic Mechanism of a Glycoside Hydrolase Family-127 β-L-Arabinofuranosidase (HypBA1).'' J Bioprocess Biotech. 2014 4:171 [http://dx.doi.org/10.4172/2155-9821.1000171 DOI:10.4172/2155-9821.1000171]
# Tsuda2015 pmid=26632508
# Barbirz2008 pmid=18547389
# Tanaka2019 pmid=30926603

</biblio>

[[Category:Definitions and explanations]]

Syn/anti lateral protonation

2019-12-21T20:44:45Z

Wim Nerinckx: Half-yearly scan/update as promised. GH156 are syn protonators.

{{CuratorApproved}}
* [[Author]]: ^^^Wim Nerinckx^^^
* [[Responsible Curator]]: ^^^Spencer Williams^^^

----

== Overview ==

This page provides a table that summarizes the spatial positioning of the catalytic [[general acid]] residue in the active sites of [[glycoside hydrolase]]s, relative to the substrate. The table below updates those found in the seminal paper on this concept by Heightman and Vasella <cite>HeightmanVasella1999</cite>, and a following paper by Nerinckx ''et al.'' <cite>Nerinckx2005</cite>.

== Background ==

The ''"not from above, but from the side"'' concept of semi-lateral glycosidic oxygen [[General_acid/base|protonation]] by [[glycoside hydrolase]]s was introduced by Heightman and Vasella <cite>HeightmanVasella1999</cite>. It was originally only described for [[Anomeric centre (alpha and beta)|beta]]-equatorial [[glycoside hydrolase]]s, but appears to be equally applicable to enzymes acting on an [[Anomeric centre (alpha and beta)|alpha]]-axial glycosidic bond <cite>Nerinckx2005</cite>. When dividing [[Sub-site nomenclature|subsite -1]] into half-spaces by a plane defined by the glycosidic oxygen and C1' and H1' of the –1 glycoside, many ligand-complexed structures reveal that the [[General_acid/base|proton donor]] is positioned either in the ''syn'' half-space (near the ring-oxygen of the –1 glycoside), or in the ''anti'' half-space (on the opposite side of the ring-oxygen). Members of the same GH [[Families|family]] appear to share a common ''syn'' or ''anti'' [[General_acid/base|protonator]] arrangement and further, this specificity appears to be preserved within [[Clans|Clans]] of [[Families|families]]. This page's compilation of [[Sub-site nomenclature|subsite -1]] occupied complexes shows that about 70% of all GH [[Families|families]] are ''anti'' [[General_acid/base|protonators]].

Closer inspection of crystal structures of [[Sub-site nomenclature|–1/+1 subsite]]-spanning substrates, or substrate-analogue ligands, in complex with enzymes reveals a further intriguing corollary <cite>Nerinckx2005 Wu2012</cite>. In substrate-bound complexes with ''anti'' [[General_acid/base|protonating]] GH enzymes, the scissile [[Anomeric centre (alpha and beta)|anomeric bond]] (often studied using the thio-analogue) shows a dihedral angle φ (O5'-C1'-[O,S]x-Cx) that is in the lowest-energy synclinal (gauche) conformation. The rationale for this is that a minus synclinal dihedral angle φ for an equatorial glycosidic bond, or plus synclinal for an axial glycosidic bond <cite>Perez1978</cite>, allows for hyperconjugative overlap of the C1'-O5' antibonding orbital with an antiperiplanar-oriented lone pair orbital lobe of the glycosidic oxygen, thereby creating partial double bond character and stabilization of the glycosidic bond by 4–5 kcal/mol; this ground-state stabilizing phenomenon is known as the ‘exo-anomeric effect’ <cite>Cramer1997 Johnson2009 Alonso2016</cite>. ''Anti'' [[General_acid/base|protonation]] occurs on the glycosidic oxygen’s antiperiplanar lone pair, thereby removing the stabilizing exo-anomeric effect. This suggests that ''anti'' [[General_acid/base|protonation]] is an enzymic approach for lowering the activation barrier leading to the [[Transition state|transition state]] (Figure 1 centre).

''Syn'' [[General_acid/base|protonating]] [[glycoside hydrolase]]s apparently make use of a different approach <cite>Nerinckx2005 Wu2012</cite>. In many [[Sub-site nomenclature|–1/+1 subsite]]-spanning ligand complexes, the dihedral angle φ of the scissile anomeric bond has been rotated away from its lowest-energy synclinal position: clockwise to minus-anticlinal or antiperiplanar for beta-equatorial; counterclockwise to plus-anticlinal or antiperiplanar for alpha-axial [[Anomeric centre (alpha and beta)|anomeric bonds]]. This removes the hyperconjugative overlap and thus also the stabilizing exo-anomeric effect. And because of this rotation, a lone pair of the glycosidic oxygen is directed into the ''syn'' half-space, allowing it to be protonated by the ''syn''-positioned [[General_acid/base|proton donor]] (Figure 1 right).

[[File:Syn_anti.jpg|800px|thumb|center|Figure 1. Newman projections, with the glycosidic oxygen as proximal atom and the anomeric carbon as distal atom, showing ''anti'' (centre) versus ''syn'' (right) semi-lateral [[General_acid/base|protonation]] in beta-equatorial (top) and alpha-axial (bottom) [[glycoside hydrolase]]s. The indicated φ is the dihedral angle for O5'-C1'-O4-C4.]]

== Table of ''syn/anti'' protonation examples ==

This table contains only one example per GH [[Families|family]] of a ligand-complexed protein structure where the ''syn'' or ''anti'' positioning of the [[General_acid/base|proton donor]] can be clearly observed; other examples may be available on a [[Families|family-by-family]] basis. The reader is thus advised to consult the [http://www.cazy.org/fam/acc_GH.html#table CAZy database] for a current, comprehensive list of CAZyme structures. Where available, the selected examples are Michaelis-type complexes with the ligand spanning the [[Sub-site nomenclature|-1/+1 subsites]], since these have an intact glycosidic or thioglycosidic bond, or are ''N''-analogs of the substrate (''e.g.'' acarbose). In some examples, the [[General_acid/base|proton donor]] has been mutated (''e.g.'', to the corresponding amide or to an alanine), and in those cases one may wish to look at a superposition of the given PDB example with the structure of the native enzyme. If a Michaelis-type complex is not yet available, the second and third example choices, respectively, are trapped glycosyl-enzyme [[intermediate]]s and product complexes where [[Sub-site nomenclature|subsite -1]] is occupied.

''Please also be aware that this is a large table with many data. Please contact the page Author or Responsible Curator with corrections.''

=== Table ===
This table can be re-sorted by clicking on the icons in the header (''javascript must be turned on in your browser''). To reset the page to be sorted by GH family, click the ''View'' tab at the very top of the page.

{| {{Prettytable}} class="sortable"
|- valign="top"
! '''Family'''
! '''Clan'''
! '''Structure fold '''
! '''Anomeric specificity'''
! '''Mechanism'''
! '''''Syn/anti'' protonator'''
! '''Example PDB ID'''
! '''Enzyme'''
! '''Organism'''
! '''Ligand'''
! '''General acid'''
! '''Nucleophile or General base'''
! '''Reference'''
|-
| [[GH1]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2cer 2cer]
| β-glycosidase S
| ''Sulfolobus solfataricus'' P2
| phenethyl glucoimidazole
| '''Glu206'''
| Glu387
| <cite>Gloster2006</cite>
|-
| [[GH2]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vzu 2vzu]
| exo-β-glucosaminidase
| ''Amicolatopsis orientalis''
| PNP-β-{{Smallcaps|d}}-glucosamine
| '''Glu469'''
| Glu541
| <cite>van_Bueren2009</cite>
|-
| [[GH3]]
| none
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1iex 1iex]
| exo-1,3-1,4-glucanase
| ''Hordeum vulgare''
| thiocellobiose
| '''Glu491'''
| Asp285
| <cite>Hrmova2001</cite>
|-
| [[GH4]]
| none
| Rossmann + α6/β3 + β3/α4
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1u8x 1u8x]
| 6-P-α-glucosidase
| ''Bacillus subtilis''
| alpha-{{Smallcaps|d}}-glucose-6-phosphate
| '''Asp172'''
| Not applicable
| <cite>Rajan2004</cite>
|-

| [[GH5]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1h2j 1h2j]
| endo-β-1,4-glucanase
| ''Bacillus agaradhaerens''
| 2',4'-DNP-2-F-cellobioside
| '''Glu129'''
| Glu228
| <cite>Varrot2003</cite>
|-
| [[GH6]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1qjw 1qjw]
| cellobiohydrolase 2
| ''Hypocrea jecorina''
| (Glc)2-S-(Glc)2
| '''Asp221'''
| debated
| <cite>Zhou1999</cite>
|-
| [[GH7]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1ovw 1ovw]
| endo-1,4-glucanase
| ''Fusarium oxysporum''
| thio-(Glc)5
| '''Glu202'''
| Glu197
| <cite>Sulzenbacher1999</cite>
|-
| [[GH8]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1kwf 1kwf]
| endo-1,4-glucanase
| ''Clostridium thermocellum''
| cellopentaose
| '''Glu95'''
| Asp278
| <cite>Guerin2002</cite>
|-
| [[GH9]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1rq5 1rq5]
| cellobiohydrolase
| ''Clostridium thermocellum''
| cellotetraose
| '''Glu795'''
| Asp383
| <cite>Schubot2004</cite>
|-
| [[GH10]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2d24 2d24]
| β-1,4-xylanase
| ''Streptomyces olivaceoviridis'' E-86
| xylopentaose
| '''Glu128'''
| Glu236
| <cite>Suzuki2009</cite>
|-
| [[GH11]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}4hk8 4hk8]
| endo-β-1,4-xylanase
| ''Hypocrea jecorina''
| xylohexaose
| '''Glu177'''
| Glu86
| <cite>Wan2014</cite>
|-
| [[GH12]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1w2u 1w2u]
| endoglucanase
| ''Humicola grisea''
| thiocellotetraose
| '''Glu205'''
| Glu120
| <cite>Sandgren2004</cite>
|-
| [[GH13]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1cxk 1cxk]
| β-cyclodextrin glucanotransferase
| ''Bacillus circulans''
| maltononaose
| '''Glu257'''
| Asp229
| <cite>Uitdehaag1999</cite>
|-
| [[GH14]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1itc 1itc]
| β-amylase
| ''Bacillus cereus''
| maltopentaose
| '''Glu172'''
| Glu367
| <cite>Miyake2003</cite>
|-
| [[GH15]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1dog 1dog]
| glucoamylase
| ''Aspergillus awamori''
| 1-deoxynojirimycin
| '''Glu179'''
| Glu400
| <cite>Harris1993</cite>
|-
| [[GH16]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1urx 1urx]
| β-agarase A
| ''Zobellia galactanivorans''
| oligoagarose
| '''Glu152'''
| Glu147
| <cite>Allouch2004</cite>
|-
| [[GH17]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzj 4gzj]
| endo-β-1,3-glucanase
| ''Solanum tuberosum''
| laminaratriose + laminarabiose
| '''Glu118'''
| Glu259
| <cite>Wojtkowiak2013</cite>
|-
| [[GH18]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1ffr 1ffr]
| chitinase A
| ''Serratia marcescens''
| (NAG)6
| '''Glu315'''
| internal
| <cite>Papanikolau2001</cite>
|-
| [[GH19]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}3wh1 3wh1]
| chitinase
| ''Bryum coronatum''
| (GlcNAc)4
| '''Glu61'''
| Glu70
| <cite>Ohnuma2014</cite>
|-
| [[GH20]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1c7s 1c7s]
| chitobiase
| ''Serratia marcescens''
| chitobiose
| '''Glu540'''
| internal
| <cite>Prag2000</cite>
|-
| [[GH22]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1h6m 1h6m]
| lysozyme C
| ''Gallus gallus''
| Chit-2-F-chitosyl
| '''Glu35'''
| Asp52
| <cite>Vocadlo2001</cite>
|-
| [[GH23]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1lsp 1lsp]
| lysozyme G
| ''Cygnus atratus''
| Bulgecin A
| '''Glu73'''
| internal
| <cite>Karlsen1996</cite>
|-
| [[GH24]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}148l 148l]
| lysozyme E
| Bacteriophage T4
| chitobiosyl
| '''Glu11'''
| Glu26
| <cite>Baldwin1993</cite>
|-
| [[GH26]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vx6 2vx6]
| exo-β-mannanase
| ''Cellvibrio japonicus'' Ueda107
| Gal1Man4
| '''Glu221'''
| Glu338
| <cite>Cartmell2008</cite>
|-
| [[GH27]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}} / beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3lrm 3lrm]
| α-galactosidase
| ''Saccharomyces cerevisiae''
| raffinose
| '''Asp209'''
| Asp141
| <cite>Fernandez-Leiro2010</cite>
|-
| [[GH28]]
| N
| β-helix
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}2uvf 2uvf]
| exo-polygalacturonosidase
| ''Yersinia enterocolitica'' ATCC9610D
| digalacturonic acid
| '''Asp402'''
| Asp381 Asp403
| <cite>Abbott2007</cite>
|-
| [[GH29]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| '''''syn'''''
| [{{PDBlink}}3uet 3uet]
| α-1,3/4-fucosidase
| ''Bifidobacterium longum'' subsp. infantis
| lacto-''N''-fucopentaose II
| '''Glu217'''
| Asp172
| <cite>Sakurama2012</cite>
|-
| [[GH30]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2y24 2y24]
| glucurono-xylanase
| ''Dickea chrysanthemi'' D1
| glucuronoxylan tetrasaccharide
| '''Glu163'''
| Glu253
| <cite>Urbanikova2011</cite>
|-
| [[GH31]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2qmj 2qmj]
| maltase-glucoamylase
| ''Homo sapiens''
| acarbose
| '''Asp542'''
| Asp443
| <cite>Sim2008</cite>
|-
| [[GH32]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2add 2add]
| fructan β-(2,1)-fructosidase
| ''Cichorium intybus''
| sucrose
| '''Glu201'''
| Asp22
| <cite>Verhaest2007</cite>
|-
| [[GH33]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1s0i 1s0i]
| transsialidase
| ''Trypanosoma cruzi''
| sialyllactose
| '''Asp59'''
| Tyr342
| <cite>Amaya2004</cite>
|-
| [[GH34]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzw 4gzw]
| N2 neuraminidase
| ''Influenza'' A Tanzania/205/2010 H3N2
| α-{{Smallcaps|d}}-Neup5Ac-(2,3)-β-{{Smallcaps|d}}-Galp-(1,4)-β-{{Smallcaps|d}}-GlcpNAc
| '''Asp151'''
| Tyr406
| <cite>Zhu2012</cite>
|-
| [[GH35]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3ogv 3ogv]
| β-galactosidase
| ''Hypocrea jecorina''
| 2-phenylethyl 1-thio-β-{{Smallcaps|d}}-galactopyranoside
| '''Glu200'''
| Glu298
| <cite>Maksimainen2011</cite>
|-
| [[GH36]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4fnu 4fnu]
| β-galactosidase
| ''Geobacillus stearothermophilus''
| stachyose
| '''Asp584'''
| Asp478
| <cite>Merceron2012</cite>
|-
| [[GH37]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2jf4 2jf4]
| trehalase
| ''Escherichia coli''
| validoxylamine
| '''Asp312'''
| Glu496
| <cite>Gibson2007</cite>
|-
| [[GH38]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3czn 3czn]
| Golgi α-mannosidase II
| ''Drosophila melanogaster''
| GlcNAcMan(5)GlcNAc(2)
| '''Asp341'''
| Asp204
| <cite>Shah2008</cite>
|-
| [[GH39]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2bfg 2bfg]
| β-xylosidase
| ''Geobacillus stearothermophilus''
| 2,5-dinitrophenyl-β-{{Smallcaps|d}}-xyloside
| '''Glu160'''
| Glu278
| <cite>Czjzek2005</cite>
|-
| [[GH42]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ucf 4ucf]
| β-galactosidase
| ''Bifidobacterium bifidum''
| {{Smallcaps|d}}-galactose
| '''Glu161'''
| Glu320
| <cite>Godoy2016</cite>
|-
| [[GH43]]
| F
| 5-fold β-propeller
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3akh 3akh]
| exo-1,5-α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces avermitilis''
| α-1,5-arabinofuranotriose
| '''Glu196'''
| Asp220
| <cite>Fujimoto2010</cite>
|-
| [[GH44]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2eqd 2eqd]
| endoglucanase
| ''Clostridium thermocellum''
| cellooctaose
| '''Glu186'''
| Glu359
| <cite>Kitago2007</cite>
|-
| [[GH45]]
| none
| 6-stranded β-barrel
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4eng 4eng]
| endo-1,4-glucanase
| ''Humicola insolens''
| cellohexaose
| '''Asp121'''
| Asp10
| <cite>Davies1996</cite>
|-
| [[GH46]]
| I
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4olt 4olt]
| chitosanase
| ''Microbacterium sp.'' OU01
| hexa-glucosamine
| '''Glu25'''
| Asp43
| <cite>Lyu2014</cite>
|-
| [[GH47]]
| none
| (α/α)7
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1x9d 1x9d]
| α-mannosidase I
| ''Homo sapiens''
| Me-2-S-(α-Man)-2-thio-α-Man
| '''Asp463'''
| Glu599
| <cite>Karaveg2005</cite>, <cite>Nerinckx2008</cite>
|-
| [[GH48]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH8''
|
|
|
|
|
|
|-
| [[GH49]]
| N
| β-helix
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH28''
|
|
|
|
|
|
|-
| [[GH50]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4bq5 4bq5]
| exo-β-agarase
| ''Saccharophagus degradans''
| neoagarotetraose
| '''Glu535'''
| Glu695
| <cite>Pluvinage2013</cite>
|-
| [[GH51]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1qw9 1qw9]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Geobacillus stearothermophilus''
| PNP-{{Smallcaps|l}}-arabinofuranoside
| '''Glu175'''
| Glu294
| <cite>Hoevel2003</cite>
|-
| [[GH52]]
| O
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4c1p 4c1p]
| β-xylosidase
| ''Geobacillus thermoglucosidasius''
| xylobiose
| '''Asp517'''
| Glu537
| <cite>Espina2014</cite>
|-
| [[GH53]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2ccr 2ccr]
| β-1,4-galactanase
| ''Bacillus licheniformis''
| galactotriose
| '''Glu165'''
| Glu263
| <cite>Le_Nours2009</cite>
|-
| [[GH54]]
| none
| β-sandwich
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1wd4 1wd4]
| α-{{Smallcaps|l}}-arabinofuranosidase B
| ''Aspergillus kawachii''
| {{Smallcaps|l}}-arabinofuranose
| '''Asp297'''
| Glu221
| <cite>Miyanaga2004</cite>
|-
| [[GH55]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4tz5 4tz5]
| exo-β-1,3-glucanase
| ''Streptomyces sp.'' SirexAA-E
| laminarihexaose
| '''Glu502'''
| unknown
| <cite>Bianchetti2015</cite>
|-
| [[GH56]]
| none
| (β/α)7
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1fcv 1fcv]
| hyaluronidase
| ''Apis mellifera''
| (hyaluron.)4
| '''Glu113'''
| internal
| <cite>Markovic-Housley2000</cite>
|-
| [[GH57]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1k1y 1k1y]
| glucanotransferase
| ''Thermococcus litoralis''
| acarbose
| '''Asp214'''
| Glu123
| <cite>Imamura2003</cite>
|-
| [[GH59]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ccc 4ccc]
| β-galactocerebrosidase
| ''Mus musculus''
| PNP-β-{{Smallcaps|d}}-galactoside
| '''Glu182'''
| Glu258
| <cite>Hill2013</cite>
|-
| [[GH62]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3wn0 3wn0]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces coelicolor''
| β-{{Smallcaps|l}}-Arabinofuranose
| '''Glu361'''
| Asp202
| <cite>Maehara2014</cite>
|-
| [[GH63]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5ca3 5ca3]
| α-glucosidase
| ''Escherichia coli''
| glucose and lactose
| '''Asp501'''
| Glu727
| <cite>Miyazaki2016</cite>
|-
| [[GH65]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}4ktr 4ktr]
| 2-O-α-glucosylglycerol phosphorylase
| ''Bacillus selenitireducens''
| isofagomine
| '''Glu475'''
| phosphate
| <cite>Touhara2014</cite>
|-
| [[GH66]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5axh 5axh]
| dextranase
| ''Thermoanaerobacter pseudethanolicus''
| isomaltohexaose
| '''Glu374'''
| Asp312
| <cite>Suzuki2016</cite>
|-
| [[GH67]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1l8n 1l8n]
| α-glucuronidase
| ''Geobacillus stearothermophilus''
| 4-O-methyl-{{Smallcaps|d}}-glucuronic acid and xylotriose
| '''Glu286'''
| Asp364 Glu392
| <cite>Golan2004</cite>
|-
| [[GH68]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1pt2 1pt2]
| levansucrase
| ''Bacillus subtilis''
| sucrose
| '''Glu342'''
| Asp86
| <cite>Meng2003</cite>
|-
| [[GH70]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3aic 3aic]
| glucansucrase
| ''Streptococcus mutans''
| α-acarbose
| '''Glu515'''
| Asp477
| <cite>Ito2011</cite>
|-
| [[GH72]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w62 2w62]
| β-1,3-glucanotransferase
| ''Saccharomyces cerevisiae'' S288C
| laminaripentaose
| '''Glu176'''
| Glu275
| <cite>Hurtado-Gerrero2009</cite>
|-
| [[GH74]]
| none
| 7-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}2ebs 2ebs]
| cellobiohydrolase (OXG-RCBH)
| ''Geotrichum sp.'' m128
| xyloglucan heptasaccharide
| '''Asp465'''
| Asp35
| <cite>Yaoi2007</cite>
|-
| [[GH76]]
| none
| (α/α)6
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5agd 5agd]
| endo-α-1,6-mannanase
| ''Bacillus circulans''
| α-1,6-mannopentaose
| '''Asp125'''
| Asp124
| <cite>Thompson2015</cite>
|-
| [[GH77]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2oww 2oww]
| 4-α-glucanotransferase
| ''Thermus thermofilus''
| acarbose + 4-deoxy-α-{{Smallcaps|d}}-glucose
| '''Glu340'''
| Asp293
| <cite>Barends2007</cite>
|-
| [[GH78]]
| H
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3w5n 3w5n]
| α-{{Smallcaps|l}}-rhamnosidase
| ''Streptomyces avermitilis''
| {{Smallcaps|l}}-rhamnose
| '''Glu636'''
| Glu895
| <cite>Fujimoto2013</cite>
|-
| [[GH79]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5e9c 5e9c]
| heparanase
| ''Homo sapiens''
| heparin tetrasaccharide
| '''Glu225'''
| Glu343
| <cite>Wu2015</cite>
|-
| [[GH80]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH24''
|
|
|
|
|
|
|-
| [[GH81]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5t4g 5t4g]
| endo-β-1,3-glucanase
| ''Bacillus halodurans'' C-125
| laminarin
| '''Asp466'''
| Glu542
| <cite>Pluvinage2017</cite>
|-
| [[GH83]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1z4x 1z4x]
| hemagglutinin-neuraminidase
| Simian virus 5
| α-2,3-sialyllactose
| '''Glu247''' relay
| Tyr523
| <cite>Yuan2005</cite>
|-
| [[GH84]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2chn 2chn]
| β-''N''-acetyl-glucosaminidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| NAG-thiazoline
| '''Glu242'''
| internal
| <cite>Dennis2006</cite>
|-
| [[GH85]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w92 2w92]
| endo-β-''N''-acetyl-glucosaminidase D
| ''Streptococcus pneumoniae'' TIGR4
| NAG-thiazoline
| '''Glu337'''
| internal
| <cite>Abbott2009</cite>
|-
| [[GH86]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4aw7 4aw7]
| β-porphyranase
| ''Bacteroides plebeius''
| porphyran fragment
| '''Glu152'''
| Glu279
| <cite>Hehemann_1_2012</cite>
|-
| [[GH89]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vcb 2vcb]
| α-''N''-acetyl-glucosaminidase
| ''Clostridium perfringens''
| PUGNAc
| '''Glu483'''
| Glu601
| <cite>Ficko-Blean2008</cite>
|-
| [[GH92]]
| none
| (α/α)6 and β-sandwich
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ww1 2ww1]
| α-1,2-mannosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| thiomannobioside
| '''Glu533'''
| Asp644 Asp642
| <cite>Zhu2009</cite>
|-
| [[GH93]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3a72 3a72]
| exo-arabinanase
| ''Penicillium chrysogenum''
| arabinobiose
| '''Glu246'''
| Glu174
| <cite>Sogabe2011</cite>
|-
| [[GH94]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4zli 4zli]
| cellobionic acid phosphorylase
| ''Saccharophagus degradans''
| 3-O-β-{{Smallcaps|d}}-glucopyranosyl-α-{{Smallcaps|d}}-glucopyranuronic acid
| '''Asp472'''
| phosphate
| <cite>Nam2015</cite>
|-
| [[GH95]]
| none
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ead 2ead]
| α-1,2-{{Smallcaps|l}}-fucosidase
| ''Bifidobacterium bifidum''
| Fuc-α-1,2-Gal
| '''Glu566'''
| Asn423 Asp766
| <cite>Nagae2007</cite>
|-
| [[GH97]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining + inverting
| '''''anti'''''
| [{{PDBlink}}2zq0 2zq0]
| α-glucosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| acarbose
| '''Glu532'''
| Glu508
| <cite>Kitamura2008</cite>
|-
| [[GH98]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2wmg 2wmg]
| endo-β-1,4-galactosidase
| ''Streptococcus pneumoniae''
| A-LewisY pentasaccharide
| '''Glu158'''
| Asp251 Glu301
| <cite>Higgins2009</cite>
|-
| [[GH99]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ad4 4ad4]
| endo-α-mannosidase
| ''Bacteroides xylanisolvens''
| glucose-1,3-isofagomine and α-1,2- mannobiose
| '''Glu336'''
| debated
| <cite>Thompson2012</cite>
|-
| [[GH100]]
| none
| (α/α)6 core
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5gop 5gop]
| invertase
| ''Anabaena (Nostoc) sp.'' pcc7120
| sucrose
| '''Asp188'''
| Glu414
| <cite>Xie2016</cite>
|-
| [[GH102]]
| none
| double-ψ β-barrel
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}2pi8 2pi8]
| lytic transglycosylase A
| ''Escherichia coli''
| chitohexaose
| '''Asp308'''
| none
| <cite>van_Straaten2007</cite>
|-
| [[GH103]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1d0k 1d0k]
| lytic transglycosylase SLT35
| ''Escherichia coli''
| murodipeptides
| '''Glu162'''
| internal
| <cite>van_Asselt2000</cite>
|-
| [[GH106]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5mwk 5mwk]
| α-{{Smallcaps|l}}-rhamnosidase BT_0986
| ''Bacteroides thetaiotaomicron''
| pectin heptasaccharide
| '''Glu461'''
| Glu593 or Glu561
| <cite>Ndeh2017</cite>
|-
| [[GH107]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| ''predicted syn by clan''
| ''see at GH29''
|
|
|
|
|
|
|-
| [[GH113]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4cd8 4cd8]
| β-mannanase
| ''Alicyclobacillus acidocaldarius''
| mannobioimidazole
| '''Glu151'''
| Glu231
| <cite>Williams2014</cite>
|-
| [[GH116]]
| O
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at GH52''
|
|
|
|
|
|
|-
| [[GH117]]
| none
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}4ak7 4ak7]
| α-1,3-3,6-anhydro-{{Smallcaps|l}}-galactosidase
| ''Bacteroides plebeius''
| neoagarobiose
| '''His302'''
| Asp90
| <cite>Hehemann_2_2012</cite>
|-
| [[GH120]]
| none
| parallel β-helix and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3vsv 3vsv]
| β-xylosidase XylC
| ''Thermoanaerobacterium saccharolyticum'' JW/SL-YS485
| {{Smallcaps|d}}-xylose
| '''Glu405'''
| Asp382
| <cite>Huang2012</cite>
|-
| [[GH123]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5fr0 5fr0]
| exo-β-N-acetyl-galactosaminidase
| ''Clostridium perfringens''
| ''N''-difluoroacetyl-{{Smallcaps|d}}-galactosamine
| '''Glu345'''
| internal
| <cite>Noach2016</cite>
|-
| [[GH125]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5m7y 5m7y]
| exo-α-1,6-mannosidase
| ''Clostridium perfringens''
| 1,6-α-mannotriose
| '''Asp220'''
| Glu393
| <cite>Alonso-Gil2016</cite>
|-
| [[GH127]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3wrg 3wrg]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bifidobacterium longum''
| {{Smallcaps|l}}-arabinose
| '''Glu322'''
| Cys417
| <cite>Huang2014</cite>
|-
| [[GH128]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH1''
|
|
|
|
|
|
|-
| [[GH130]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5b0s 5b0s]
| β-1,2-mannobiose phosphorylase
| ''Listeria innocua''
| β-1,2-mannotriose
| '''Asp141''' relay
| phosphate
| <cite>Tsuda2015</cite>
|-
| [[GH134]]
| none
| β + α
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5jug 5jug]
| β-mannanase
| ''Streptomyces sp.''
| mannopentaose
| '''Glu45'''
| Asp57
| <cite>Jin2016</cite>
|-
| [[GH136]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}5gqf 5gqf]
| lacto-N-biosidase
| ''Bifidobacterium longum''
| lacto-N-biose
| '''Asp411'''
| Asp418
| <cite>Yamada2017</cite>
|-
| [[GH137]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|l}}
| unknown
| '''''anti'''''
| [{{PDBlink}}5mui 5mui]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0996
| ''Bacteroides thetaiotaomicron''
| pectin oligosaccharide
| '''Glu240'''
| Glu159
| <cite>Ndeh2017</cite>

|-
| [[GH138]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}6hzg 6hzg]
| α-1,2-{{Smallcaps|d}}-galacturonidase
| ''Bacteroides paurosaccharolyticus''
| alpha-{{Smallcaps|d}}-galactopyranuronic
| '''Glu294'''
| Glu361
| <cite>Labourel2019</cite>
|-
| [[GH146]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5opj 5opj]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0349
| ''Bacteroides thetaiotaomicron''
| {{Smallcaps|l}}-arabinose
| '''Glu320'''
| Cys416
| <cite>Luis2018</cite>
|-
| [[GH147]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH148]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH149]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH156]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}6s0e 6s0e]
| exo-α-sialidase
| uncultured bacterium pG7
| N-acetyl-2,3-dehydro-2-deoxyneuraminic acid
| '''His134'''
| Asp14
| <cite>Bule2019</cite>

|-
| [[GH157]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-

| [[GH158]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH161]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH162]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}6imw 6imw]
| endo-β-1,2-glucanase
| ''Talaromyces funiculosus''
| beta-1,2-glucan
| '''Glu262''' via C3-OH of glc at subs. +2
| Asp446
| <cite>Tanaka2019</cite>
|-
| [http://www.cazy.org/GH0.html n.c.*]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2vjj 2vjj]
| endo-α-N-acetylglucosaminidase
| Bacteriophage HK620
| O18A1 O-antigen hexasaccharide
| '''Asp339'''
| Glu372
| <cite>Barbirz2008</cite>
|}
<nowiki>*</nowiki> n.c.: Found among the collection of [http://www.cazy.org/GH0.html non-classified GH sequences in the CAZy Database].

== References ==

<biblio>
# HeightmanVasella1999 Heightman TD and Vasella AT. ''Recent Insights into Inhibition, Structure, and Mechanism of Configuration-Retaining Glycosidases.'' Angew Chem Int Ed. 1999 38(6):750-770. [http://www3.interscience.wiley.com/journal/55000581/abstract Article online].
# Nerinckx2005 pmid=15642336
# Wu2012 pmid=23137336
# Perez1978 Pérez S and Marchessault RH. ''The exo-anomeric effect: experimental evidence from crystal structures.'' Carbohydr res. 1978 65:114-120. [http://dx.doi.org/10.1016/S0008-6215(00)84218-4 DOI:10.1016/S0008-6215(00)84218-4]
# Cramer1997 Cramer CJ, Truhlar DG, and French AD. ''Exo-anomeric effects on energies and geometries of different conformations of glucose and related systems in the gas phase and aqueous solution.'' Carbohydr res. 1997 298:1-14. [http://dx.doi.org/10.1016/S0008-6215(96)00297-2 DOI:10.1016/S0008-6215(96)00297-2]
# Johnson2009 pmid=19733839
# Alonso2016 pmid=26889578
# Gloster2006 pmid=17002288
# van_Bueren2009 pmid=18976664
# Hrmova2001 pmid=11709165

# Rajan2004 pmid=15341727
# Varrot2003 pmid=12595701
# Zhou1999 pmid=10508787
# Sulzenbacher1999 pmid=10200171
# Urbanikova2011 pmid=21501386
# Guerin2002 pmid=11884144
# Schubot2004 pmid=14756552
# Suzuki2009 pmid=19279191
# Wan2014 pmid=24419374
# Sandgren2004 pmid=15364577
# Uitdehaag1999 pmid=10331869
# Miyake2003 pmid=12741813
# Harris1993 pmid=8431441
# Allouch2004 pmid=15062085
# Wojtkowiak2013 pmid=23275163
# Papanikolau2001 pmid=11560481
# Prag2000 pmid=10884356
# Vocadlo2001 pmid=11518970
# Karlsen1996 pmid=15299731
# Baldwin1993 pmid=8259514
# Cartmell2008 pmid=18799462
# Fernandez-Leiro2010 pmid=20592022
# Abbott2007 pmid=17397864
# Sakurama2012 pmid=22451675
# Sim2008 pmid=18036614
# Verhaest2007 pmid=17335500
# Amaya2004 pmid=15130470
# Zhu2012 pmid=23015718
# Maksimainen2011 pmid=21130883
# Merceron2012 pmid=23012371
# Gibson2007 pmid=17455176
# Shah2008 pmid=18599462
# Czjzek2005 pmid=16212978
# Godoy2016 pmid=27685756
# Fujimoto2010 pmid=20739278
# Kitago2007 pmid=17905739
# Davies1996 pmid=15299721
# Lyu2014 pmid=24766439
# Karaveg2005 pmid=15713668
# Nerinckx2008 pmid=18619586
# Pluvinage2013 pmid=23921382

# Yuan2005 pmid=15893670
# Hoevel2003 pmid=14517232
# Espina2014 pmid=24816105
# Le_Nours2009 pmid=19089956
# Miyanaga2004 pmid=15292273
# Bianchetti2015 pmid=25752603
# Markovic-Housley2000 pmid=11080624
# Imamura2003 pmid=12618437
# Hill2013 pmid=24297913

# Maehara2014 pmid=24482228

# Miyazaki2016 pmid=27688023
# Touhara2014 pmid=24828502
# Suzuki2016 pmid=26494689
# Golan2004 pmid=14573597
# Meng2003 pmid=14517548
# Ito2011 pmid=21354427
# Hurtado-Gerrero2009 pmid=19097997
# Yaoi2007 pmid=17498741
# Thompson2015 pmid=25772148
# Barends2007 pmid=17420245
# Fujimoto2013 pmid=23486481
# Wu2015 pmid=26575439
# Pluvinage2017 pmid=28781080
# Dennis2006 pmid=16565725
# Abbott2009 pmid=19181667
# Hehemann_1_2012 pmid=23150581
# Ficko-Blean2008 pmid=18443291
# Zhu2009 pmid=20081828
# Sogabe2011 pmid=21543843
# Nam2015 pmid=26041776
# Nagae2007 pmid=17459873
# Kitamura2008 pmid=18981178
# Higgins2009 pmid=19608744
# van_Straaten2007 pmid=17502382
# van_Asselt2000 pmid=10684641
# Ndeh2017 pmid=28329766
# Labourel2019 pmid=30877196
# Luis2018 pmid=29255254

# Bule2019 pmid=31645552

# Jin2016 Jin Y, Petricevic M, John A, Raich L, Jenkins H, Portela De Souza L, Cuskin F, Gilbert HJ, Rovira C, Goddard-Borger ED, Williams SJ, and Davies GJ. ''A β-Mannanase with a Lysozyme-like Fold and a Novel Molecular Catalytic Mechanism.'' ACS Cent Sci. 2016 Nov [http://dx.doi.org/10.1021/acscentsci.6b00232 DOI:10.1021/acscentsci.6b00232]
# Yamada2017 pmid=28392148
# Ohnuma2014 pmid=24582745
# Thompson2012 pmid=22219371
# Xie2016 pmid=27777307
# Williams2014 pmid=24339341
# Hehemann_2_2012 pmid=22393053
# Huang2012 pmid=22992047
# Noach2016 pmid=27038508
# Alonso-Gil2016 pmid=28026180
# Huang2014 Huang CH, Zhu Z, Cheng YS, Chan HC, Ko TP, Chen CC, Wang I, Ho MR, Hsu ST, Zeng YF, Huang YN, Liu JR, Guo RT. ''Structure and Catalytic Mechanism of a Glycoside Hydrolase Family-127 β-L-Arabinofuranosidase (HypBA1).'' J Bioprocess Biotech. 2014 4:171 [http://dx.doi.org/10.4172/2155-9821.1000171 DOI:10.4172/2155-9821.1000171]
# Tsuda2015 pmid=26632508
# Barbirz2008 pmid=18547389
# Tanaka2019 pmid=30926603

</biblio>

[[Category:Definitions and explanations]]

Syn/anti lateral protonation

2019-07-31T14:07:48Z

Wim Nerinckx: subsite -1/+1 spanning ligand

{{CuratorApproved}}
* [[Author]]: ^^^Wim Nerinckx^^^
* [[Responsible Curator]]: ^^^Spencer Williams^^^

----

== Overview ==

This page provides a table that summarizes the spatial positioning of the catalytic [[general acid]] residue in the active sites of [[glycoside hydrolase]]s, relative to the substrate. The table below updates those found in the seminal paper on this concept by Heightman and Vasella <cite>HeightmanVasella1999</cite>, and a following paper by Nerinckx ''et al.'' <cite>Nerinckx2005</cite>.

== Background ==

The ''"not from above, but from the side"'' concept of semi-lateral glycosidic oxygen [[General_acid/base|protonation]] by [[glycoside hydrolase]]s was introduced by Heightman and Vasella <cite>HeightmanVasella1999</cite>. It was originally only described for [[Anomeric centre (alpha and beta)|beta]]-equatorial [[glycoside hydrolase]]s, but appears to be equally applicable to enzymes acting on an [[Anomeric centre (alpha and beta)|alpha]]-axial glycosidic bond <cite>Nerinckx2005</cite>. When dividing [[Sub-site nomenclature|subsite -1]] into half-spaces by a plane defined by the glycosidic oxygen and C1' and H1' of the –1 glycoside, many ligand-complexed structures reveal that the [[General_acid/base|proton donor]] is positioned either in the ''syn'' half-space (near the ring-oxygen of the –1 glycoside), or in the ''anti'' half-space (on the opposite side of the ring-oxygen). Members of the same GH [[Families|family]] appear to share a common ''syn'' or ''anti'' [[General_acid/base|protonator]] arrangement and further, this specificity appears to be preserved within [[Clans|Clans]] of [[Families|families]]. This page's compilation of [[Sub-site nomenclature|subsite -1]] occupied complexes shows that about 70% of all GH [[Families|families]] are ''anti'' [[General_acid/base|protonators]].

Closer inspection of crystal structures of [[Sub-site nomenclature|–1/+1 subsite]]-spanning substrates, or substrate-analogue ligands, in complex with enzymes reveals a further intriguing corollary <cite>Nerinckx2005 Wu2012</cite>. In substrate-bound complexes with ''anti'' [[General_acid/base|protonating]] GH enzymes, the scissile [[Anomeric centre (alpha and beta)|anomeric bond]] (often studied using the thio-analogue) shows a dihedral angle φ (O5'-C1'-[O,S]x-Cx) that is in the lowest-energy synclinal (gauche) conformation. The rationale for this is that a minus synclinal dihedral angle φ for an equatorial glycosidic bond, or plus synclinal for an axial glycosidic bond <cite>Perez1978</cite>, allows for hyperconjugative overlap of the C1'-O5' antibonding orbital with an antiperiplanar-oriented lone pair orbital lobe of the glycosidic oxygen, thereby creating partial double bond character and stabilization of the glycosidic bond by 4–5 kcal/mol; this ground-state stabilizing phenomenon is known as the ‘exo-anomeric effect’ <cite>Cramer1997 Johnson2009 Alonso2016</cite>. ''Anti'' [[General_acid/base|protonation]] occurs on the glycosidic oxygen’s antiperiplanar lone pair, thereby removing the stabilizing exo-anomeric effect. This suggests that ''anti'' [[General_acid/base|protonation]] is an enzymic approach for lowering the activation barrier leading to the [[Transition state|transition state]] (Figure 1 centre).

''Syn'' [[General_acid/base|protonating]] [[glycoside hydrolase]]s apparently make use of a different approach <cite>Nerinckx2005 Wu2012</cite>. In many [[Sub-site nomenclature|–1/+1 subsite]]-spanning ligand complexes, the dihedral angle φ of the scissile anomeric bond has been rotated away from its lowest-energy synclinal position: clockwise to minus-anticlinal or antiperiplanar for beta-equatorial; counterclockwise to plus-anticlinal or antiperiplanar for alpha-axial [[Anomeric centre (alpha and beta)|anomeric bonds]]. This removes the hyperconjugative overlap and thus also the stabilizing exo-anomeric effect. And because of this rotation, a lone pair of the glycosidic oxygen is directed into the ''syn'' half-space, allowing it to be protonated by the ''syn''-positioned [[General_acid/base|proton donor]] (Figure 1 right).

[[File:Syn_anti.jpg|800px|thumb|center|Figure 1. Newman projections, with the glycosidic oxygen as proximal atom and the anomeric carbon as distal atom, showing ''anti'' (centre) versus ''syn'' (right) semi-lateral [[General_acid/base|protonation]] in beta-equatorial (top) and alpha-axial (bottom) [[glycoside hydrolase]]s. The indicated φ is the dihedral angle for O5'-C1'-O4-C4.]]

== Table of ''syn/anti'' protonation examples ==

This table contains only one example per GH [[Families|family]] of a ligand-complexed protein structure where the ''syn'' or ''anti'' positioning of the [[General_acid/base|proton donor]] can be clearly observed; other examples may be available on a [[Families|family-by-family]] basis. The reader is thus advised to consult the [http://www.cazy.org/fam/acc_GH.html#table CAZy database] for a current, comprehensive list of CAZyme structures. Where available, the selected examples are Michaelis-type complexes with the ligand spanning the [[Sub-site nomenclature|-1/+1 subsites]], since these have an intact glycosidic or thioglycosidic bond, or are ''N''-analogs of the substrate (''e.g.'' acarbose). In some examples, the [[General_acid/base|proton donor]] has been mutated (''e.g.'', to the corresponding amide or to an alanine), and in those cases one may wish to look at a superposition of the given PDB example with the structure of the native enzyme. If a Michaelis-type complex is not yet available, the second and third example choices, respectively, are trapped glycosyl-enzyme [[intermediate]]s and product complexes where [[Sub-site nomenclature|subsite -1]] is occupied.

''Please also be aware that this is a large table with many data. Please contact the page Author or Responsible Curator with corrections.''

=== Table ===
This table can be re-sorted by clicking on the icons in the header (''javascript must be turned on in your browser''). To reset the page to be sorted by GH family, click the ''View'' tab at the very top of the page.

{| {{Prettytable}} class="sortable"
|- valign="top"
! '''Family'''
! '''Clan'''
! '''Structure fold '''
! '''Anomeric specificity'''
! '''Mechanism'''
! '''''Syn/anti'' protonator'''
! '''Example PDB ID'''
! '''Enzyme'''
! '''Organism'''
! '''Ligand'''
! '''General acid'''
! '''Nucleophile or General base'''
! '''Reference'''
|-
| [[GH1]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2cer 2cer]
| β-glycosidase S
| ''Sulfolobus solfataricus'' P2
| phenethyl glucoimidazole
| '''Glu206'''
| Glu387
| <cite>Gloster2006</cite>
|-
| [[GH2]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vzu 2vzu]
| exo-β-glucosaminidase
| ''Amicolatopsis orientalis''
| PNP-β-{{Smallcaps|d}}-glucosamine
| '''Glu469'''
| Glu541
| <cite>van_Bueren2009</cite>
|-
| [[GH3]]
| none
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1iex 1iex]
| exo-1,3-1,4-glucanase
| ''Hordeum vulgare''
| thiocellobiose
| '''Glu491'''
| Asp285
| <cite>Hrmova2001</cite>
|-
| [[GH4]]
| none
| Rossmann + α6/β3 + β3/α4
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1u8x 1u8x]
| 6-P-α-glucosidase
| ''Bacillus subtilis''
| alpha-{{Smallcaps|d}}-glucose-6-phosphate
| '''Asp172'''
| Not applicable
| <cite>Rajan2004</cite>
|-

| [[GH5]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1h2j 1h2j]
| endo-β-1,4-glucanase
| ''Bacillus agaradhaerens''
| 2',4'-DNP-2-F-cellobioside
| '''Glu129'''
| Glu228
| <cite>Varrot2003</cite>
|-
| [[GH6]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1qjw 1qjw]
| cellobiohydrolase 2
| ''Hypocrea jecorina''
| (Glc)2-S-(Glc)2
| '''Asp221'''
| debated
| <cite>Zhou1999</cite>
|-
| [[GH7]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1ovw 1ovw]
| endo-1,4-glucanase
| ''Fusarium oxysporum''
| thio-(Glc)5
| '''Glu202'''
| Glu197
| <cite>Sulzenbacher1999</cite>
|-
| [[GH8]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1kwf 1kwf]
| endo-1,4-glucanase
| ''Clostridium thermocellum''
| cellopentaose
| '''Glu95'''
| Asp278
| <cite>Guerin2002</cite>
|-
| [[GH9]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1rq5 1rq5]
| cellobiohydrolase
| ''Clostridium thermocellum''
| cellotetraose
| '''Glu795'''
| Asp383
| <cite>Schubot2004</cite>
|-
| [[GH10]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2d24 2d24]
| β-1,4-xylanase
| ''Streptomyces olivaceoviridis'' E-86
| xylopentaose
| '''Glu128'''
| Glu236
| <cite>Suzuki2009</cite>
|-
| [[GH11]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}4hk8 4hk8]
| endo-β-1,4-xylanase
| ''Hypocrea jecorina''
| xylohexaose
| '''Glu177'''
| Glu86
| <cite>Wan2014</cite>
|-
| [[GH12]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1w2u 1w2u]
| endoglucanase
| ''Humicola grisea''
| thiocellotetraose
| '''Glu205'''
| Glu120
| <cite>Sandgren2004</cite>
|-
| [[GH13]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1cxk 1cxk]
| β-cyclodextrin glucanotransferase
| ''Bacillus circulans''
| maltononaose
| '''Glu257'''
| Asp229
| <cite>Uitdehaag1999</cite>
|-
| [[GH14]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1itc 1itc]
| β-amylase
| ''Bacillus cereus''
| maltopentaose
| '''Glu172'''
| Glu367
| <cite>Miyake2003</cite>
|-
| [[GH15]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1dog 1dog]
| glucoamylase
| ''Aspergillus awamori''
| 1-deoxynojirimycin
| '''Glu179'''
| Glu400
| <cite>Harris1993</cite>
|-
| [[GH16]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1urx 1urx]
| β-agarase A
| ''Zobellia galactanivorans''
| oligoagarose
| '''Glu152'''
| Glu147
| <cite>Allouch2004</cite>
|-
| [[GH17]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzj 4gzj]
| endo-β-1,3-glucanase
| ''Solanum tuberosum''
| laminaratriose + laminarabiose
| '''Glu118'''
| Glu259
| <cite>Wojtkowiak2013</cite>
|-
| [[GH18]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1ffr 1ffr]
| chitinase A
| ''Serratia marcescens''
| (NAG)6
| '''Glu315'''
| internal
| <cite>Papanikolau2001</cite>
|-
| [[GH19]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}3wh1 3wh1]
| chitinase
| ''Bryum coronatum''
| (GlcNAc)4
| '''Glu61'''
| Glu70
| <cite>Ohnuma2014</cite>
|-
| [[GH20]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1c7s 1c7s]
| chitobiase
| ''Serratia marcescens''
| chitobiose
| '''Glu540'''
| internal
| <cite>Prag2000</cite>
|-
| [[GH22]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1h6m 1h6m]
| lysozyme C
| ''Gallus gallus''
| Chit-2-F-chitosyl
| '''Glu35'''
| Asp52
| <cite>Vocadlo2001</cite>
|-
| [[GH23]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1lsp 1lsp]
| lysozyme G
| ''Cygnus atratus''
| Bulgecin A
| '''Glu73'''
| internal
| <cite>Karlsen1996</cite>
|-
| [[GH24]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}148l 148l]
| lysozyme E
| Bacteriophage T4
| chitobiosyl
| '''Glu11'''
| Glu26
| <cite>Baldwin1993</cite>
|-
| [[GH26]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vx6 2vx6]
| exo-β-mannanase
| ''Cellvibrio japonicus'' Ueda107
| Gal1Man4
| '''Glu221'''
| Glu338
| <cite>Cartmell2008</cite>
|-
| [[GH27]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}} / beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3lrm 3lrm]
| α-galactosidase
| ''Saccharomyces cerevisiae''
| raffinose
| '''Asp209'''
| Asp141
| <cite>Fernandez-Leiro2010</cite>
|-
| [[GH28]]
| N
| β-helix
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}2uvf 2uvf]
| exo-polygalacturonosidase
| ''Yersinia enterocolitica'' ATCC9610D
| digalacturonic acid
| '''Asp402'''
| Asp381 Asp403
| <cite>Abbott2007</cite>
|-
| [[GH29]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| '''''syn'''''
| [{{PDBlink}}3uet 3uet]
| α-1,3/4-fucosidase
| ''Bifidobacterium longum'' subsp. infantis
| lacto-''N''-fucopentaose II
| '''Glu217'''
| Asp172
| <cite>Sakurama2012</cite>
|-
| [[GH30]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2y24 2y24]
| glucurono-xylanase
| ''Dickea chrysanthemi'' D1
| glucuronoxylan tetrasaccharide
| '''Glu163'''
| Glu253
| <cite>Urbanikova2011</cite>
|-
| [[GH31]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2qmj 2qmj]
| maltase-glucoamylase
| ''Homo sapiens''
| acarbose
| '''Asp542'''
| Asp443
| <cite>Sim2008</cite>
|-
| [[GH32]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2add 2add]
| fructan β-(2,1)-fructosidase
| ''Cichorium intybus''
| sucrose
| '''Glu201'''
| Asp22
| <cite>Verhaest2007</cite>
|-
| [[GH33]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1s0i 1s0i]
| transsialidase
| ''Trypanosoma cruzi''
| sialyllactose
| '''Asp59'''
| Tyr342
| <cite>Amaya2004</cite>
|-
| [[GH34]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzw 4gzw]
| N2 neuraminidase
| ''Influenza'' A Tanzania/205/2010 H3N2
| α-{{Smallcaps|d}}-Neup5Ac-(2,3)-β-{{Smallcaps|d}}-Galp-(1,4)-β-{{Smallcaps|d}}-GlcpNAc
| '''Asp151'''
| Tyr406
| <cite>Zhu2012</cite>
|-
| [[GH35]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3ogv 3ogv]
| β-galactosidase
| ''Hypocrea jecorina''
| 2-phenylethyl 1-thio-β-{{Smallcaps|d}}-galactopyranoside
| '''Glu200'''
| Glu298
| <cite>Maksimainen2011</cite>
|-
| [[GH36]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4fnu 4fnu]
| β-galactosidase
| ''Geobacillus stearothermophilus''
| stachyose
| '''Asp584'''
| Asp478
| <cite>Merceron2012</cite>
|-
| [[GH37]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2jf4 2jf4]
| trehalase
| ''Escherichia coli''
| validoxylamine
| '''Asp312'''
| Glu496
| <cite>Gibson2007</cite>
|-
| [[GH38]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3czn 3czn]
| Golgi α-mannosidase II
| ''Drosophila melanogaster''
| GlcNAcMan(5)GlcNAc(2)
| '''Asp341'''
| Asp204
| <cite>Shah2008</cite>
|-
| [[GH39]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2bfg 2bfg]
| β-xylosidase
| ''Geobacillus stearothermophilus''
| 2,5-dinitrophenyl-β-{{Smallcaps|d}}-xyloside
| '''Glu160'''
| Glu278
| <cite>Czjzek2005</cite>
|-
| [[GH42]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ucf 4ucf]
| β-galactosidase
| ''Bifidobacterium bifidum''
| {{Smallcaps|d}}-galactose
| '''Glu161'''
| Glu320
| <cite>Godoy2016</cite>
|-
| [[GH43]]
| F
| 5-fold β-propeller
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3akh 3akh]
| exo-1,5-α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces avermitilis''
| α-1,5-arabinofuranotriose
| '''Glu196'''
| Asp220
| <cite>Fujimoto2010</cite>
|-
| [[GH44]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2eqd 2eqd]
| endoglucanase
| ''Clostridium thermocellum''
| cellooctaose
| '''Glu186'''
| Glu359
| <cite>Kitago2007</cite>
|-
| [[GH45]]
| none
| 6-stranded β-barrel
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4eng 4eng]
| endo-1,4-glucanase
| ''Humicola insolens''
| cellohexaose
| '''Asp121'''
| Asp10
| <cite>Davies1996</cite>
|-
| [[GH46]]
| I
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4olt 4olt]
| chitosanase
| ''Microbacterium sp.'' OU01
| hexa-glucosamine
| '''Glu25'''
| Asp43
| <cite>Lyu2014</cite>
|-
| [[GH47]]
| none
| (α/α)7
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1x9d 1x9d]
| α-mannosidase I
| ''Homo sapiens''
| Me-2-S-(α-Man)-2-thio-α-Man
| '''Asp463'''
| Glu599
| <cite>Karaveg2005</cite>, <cite>Nerinckx2008</cite>
|-
| [[GH48]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH8''
|
|
|
|
|
|
|-
| [[GH49]]
| N
| β-helix
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH28''
|
|
|
|
|
|
|-
| [[GH50]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4bq5 4bq5]
| exo-β-agarase
| ''Saccharophagus degradans''
| neoagarotetraose
| '''Glu535'''
| Glu695
| <cite>Pluvinage2013</cite>
|-
| [[GH51]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1qw9 1qw9]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Geobacillus stearothermophilus''
| PNP-{{Smallcaps|l}}-arabinofuranoside
| '''Glu175'''
| Glu294
| <cite>Hoevel2003</cite>
|-
| [[GH52]]
| O
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4c1p 4c1p]
| β-xylosidase
| ''Geobacillus thermoglucosidasius''
| xylobiose
| '''Asp517'''
| Glu537
| <cite>Espina2014</cite>
|-
| [[GH53]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2ccr 2ccr]
| β-1,4-galactanase
| ''Bacillus licheniformis''
| galactotriose
| '''Glu165'''
| Glu263
| <cite>Le_Nours2009</cite>
|-
| [[GH54]]
| none
| β-sandwich
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1wd4 1wd4]
| α-{{Smallcaps|l}}-arabinofuranosidase B
| ''Aspergillus kawachii''
| {{Smallcaps|l}}-arabinofuranose
| '''Asp297'''
| Glu221
| <cite>Miyanaga2004</cite>
|-
| [[GH55]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4tz5 4tz5]
| exo-β-1,3-glucanase
| ''Streptomyces sp.'' SirexAA-E
| laminarihexaose
| '''Glu502'''
| unknown
| <cite>Bianchetti2015</cite>
|-
| [[GH56]]
| none
| (β/α)7
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1fcv 1fcv]
| hyaluronidase
| ''Apis mellifera''
| (hyaluron.)4
| '''Glu113'''
| internal
| <cite>Markovic-Housley2000</cite>
|-
| [[GH57]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1k1y 1k1y]
| glucanotransferase
| ''Thermococcus litoralis''
| acarbose
| '''Asp214'''
| Glu123
| <cite>Imamura2003</cite>
|-
| [[GH59]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ccc 4ccc]
| β-galactocerebrosidase
| ''Mus musculus''
| PNP-β-{{Smallcaps|d}}-galactoside
| '''Glu182'''
| Glu258
| <cite>Hill2013</cite>
|-
| [[GH62]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3wn0 3wn0]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces coelicolor''
| β-{{Smallcaps|l}}-Arabinofuranose
| '''Glu361'''
| Asp202
| <cite>Maehara2014</cite>
|-
| [[GH63]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5ca3 5ca3]
| α-glucosidase
| ''Escherichia coli''
| glucose and lactose
| '''Asp501'''
| Glu727
| <cite>Miyazaki2016</cite>
|-
| [[GH65]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}4ktr 4ktr]
| 2-O-α-glucosylglycerol phosphorylase
| ''Bacillus selenitireducens''
| isofagomine
| '''Glu475'''
| phosphate
| <cite>Touhara2014</cite>
|-
| [[GH66]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5axh 5axh]
| dextranase
| ''Thermoanaerobacter pseudethanolicus''
| isomaltohexaose
| '''Glu374'''
| Asp312
| <cite>Suzuki2016</cite>
|-
| [[GH67]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1l8n 1l8n]
| α-glucuronidase
| ''Geobacillus stearothermophilus''
| 4-O-methyl-{{Smallcaps|d}}-glucuronic acid and xylotriose
| '''Glu286'''
| Asp364 Glu392
| <cite>Golan2004</cite>
|-
| [[GH68]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1pt2 1pt2]
| levansucrase
| ''Bacillus subtilis''
| sucrose
| '''Glu342'''
| Asp86
| <cite>Meng2003</cite>
|-
| [[GH70]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3aic 3aic]
| glucansucrase
| ''Streptococcus mutans''
| α-acarbose
| '''Glu515'''
| Asp477
| <cite>Ito2011</cite>
|-
| [[GH72]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w62 2w62]
| β-1,3-glucanotransferase
| ''Saccharomyces cerevisiae'' S288C
| laminaripentaose
| '''Glu176'''
| Glu275
| <cite>Hurtado-Gerrero2009</cite>
|-
| [[GH74]]
| none
| 7-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}2ebs 2ebs]
| cellobiohydrolase (OXG-RCBH)
| ''Geotrichum sp.'' m128
| xyloglucan heptasaccharide
| '''Asp465'''
| Asp35
| <cite>Yaoi2007</cite>
|-
| [[GH76]]
| none
| (α/α)6
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5agd 5agd]
| endo-α-1,6-mannanase
| ''Bacillus circulans''
| α-1,6-mannopentaose
| '''Asp125'''
| Asp124
| <cite>Thompson2015</cite>
|-
| [[GH77]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2oww 2oww]
| 4-α-glucanotransferase
| ''Thermus thermofilus''
| acarbose + 4-deoxy-α-{{Smallcaps|d}}-glucose
| '''Glu340'''
| Asp293
| <cite>Barends2007</cite>
|-
| [[GH78]]
| H
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3w5n 3w5n]
| α-{{Smallcaps|l}}-rhamnosidase
| ''Streptomyces avermitilis''
| {{Smallcaps|l}}-rhamnose
| '''Glu636'''
| Glu895
| <cite>Fujimoto2013</cite>
|-
| [[GH79]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5e9c 5e9c]
| heparanase
| ''Homo sapiens''
| heparin tetrasaccharide
| '''Glu225'''
| Glu343
| <cite>Wu2015</cite>
|-
| [[GH80]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH24''
|
|
|
|
|
|
|-
| [[GH81]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5t4g 5t4g]
| endo-β-1,3-glucanase
| ''Bacillus halodurans'' C-125
| laminarin
| '''Asp466'''
| Glu542
| <cite>Pluvinage2017</cite>
|-
| [[GH83]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1z4x 1z4x]
| hemagglutinin-neuraminidase
| Simian virus 5
| α-2,3-sialyllactose
| '''Glu247''' relay
| Tyr523
| <cite>Yuan2005</cite>
|-
| [[GH84]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2chn 2chn]
| β-''N''-acetyl-glucosaminidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| NAG-thiazoline
| '''Glu242'''
| internal
| <cite>Dennis2006</cite>
|-
| [[GH85]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w92 2w92]
| endo-β-''N''-acetyl-glucosaminidase D
| ''Streptococcus pneumoniae'' TIGR4
| NAG-thiazoline
| '''Glu337'''
| internal
| <cite>Abbott2009</cite>
|-
| [[GH86]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4aw7 4aw7]
| β-porphyranase
| ''Bacteroides plebeius''
| porphyran fragment
| '''Glu152'''
| Glu279
| <cite>Hehemann_1_2012</cite>
|-
| [[GH89]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vcb 2vcb]
| α-''N''-acetyl-glucosaminidase
| ''Clostridium perfringens''
| PUGNAc
| '''Glu483'''
| Glu601
| <cite>Ficko-Blean2008</cite>
|-
| [[GH92]]
| none
| (α/α)6 and β-sandwich
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ww1 2ww1]
| α-1,2-mannosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| thiomannobioside
| '''Glu533'''
| Asp644 Asp642
| <cite>Zhu2009</cite>
|-
| [[GH93]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3a72 3a72]
| exo-arabinanase
| ''Penicillium chrysogenum''
| arabinobiose
| '''Glu246'''
| Glu174
| <cite>Sogabe2011</cite>
|-
| [[GH94]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4zli 4zli]
| cellobionic acid phosphorylase
| ''Saccharophagus degradans''
| 3-O-β-{{Smallcaps|d}}-glucopyranosyl-α-{{Smallcaps|d}}-glucopyranuronic acid
| '''Asp472'''
| phosphate
| <cite>Nam2015</cite>
|-
| [[GH95]]
| none
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ead 2ead]
| α-1,2-{{Smallcaps|l}}-fucosidase
| ''Bifidobacterium bifidum''
| Fuc-α-1,2-Gal
| '''Glu566'''
| Asn423 Asp766
| <cite>Nagae2007</cite>
|-
| [[GH97]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining + inverting
| '''''anti'''''
| [{{PDBlink}}2zq0 2zq0]
| α-glucosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| acarbose
| '''Glu532'''
| Glu508
| <cite>Kitamura2008</cite>
|-
| [[GH98]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2wmg 2wmg]
| endo-β-1,4-galactosidase
| ''Streptococcus pneumoniae''
| A-LewisY pentasaccharide
| '''Glu158'''
| Asp251 Glu301
| <cite>Higgins2009</cite>
|-
| [[GH99]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ad4 4ad4]
| endo-α-mannosidase
| ''Bacteroides xylanisolvens''
| glucose-1,3-isofagomine and α-1,2- mannobiose
| '''Glu336'''
| debated
| <cite>Thompson2012</cite>
|-
| [[GH100]]
| none
| (α/α)6 core
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5gop 5gop]
| invertase
| ''Anabaena (Nostoc) sp.'' pcc7120
| sucrose
| '''Asp188'''
| Glu414
| <cite>Xie2016</cite>
|-
| [[GH102]]
| none
| double-ψ β-barrel
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}2pi8 2pi8]
| lytic transglycosylase A
| ''Escherichia coli''
| chitohexaose
| '''Asp308'''
| none
| <cite>van_Straaten2007</cite>
|-
| [[GH103]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1d0k 1d0k]
| lytic transglycosylase SLT35
| ''Escherichia coli''
| murodipeptides
| '''Glu162'''
| internal
| <cite>van_Asselt2000</cite>
|-
| [[GH106]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5mwk 5mwk]
| α-{{Smallcaps|l}}-rhamnosidase BT_0986
| ''Bacteroides thetaiotaomicron''
| pectin heptasaccharide
| '''Glu461'''
| Glu593 or Glu561
| <cite>Ndeh2017</cite>
|-
| [[GH107]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| ''predicted syn by clan''
| ''see at GH29''
|
|
|
|
|
|
|-
| [[GH113]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4cd8 4cd8]
| β-mannanase
| ''Alicyclobacillus acidocaldarius''
| mannobioimidazole
| '''Glu151'''
| Glu231
| <cite>Williams2014</cite>
|-
| [[GH116]]
| O
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at GH52''
|
|
|
|
|
|
|-
| [[GH117]]
| none
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}4ak7 4ak7]
| α-1,3-3,6-anhydro-{{Smallcaps|l}}-galactosidase
| ''Bacteroides plebeius''
| neoagarobiose
| '''His302'''
| Asp90
| <cite>Hehemann_2_2012</cite>
|-
| [[GH120]]
| none
| parallel β-helix and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3vsv 3vsv]
| β-xylosidase XylC
| ''Thermoanaerobacterium saccharolyticum'' JW/SL-YS485
| {{Smallcaps|d}}-xylose
| '''Glu405'''
| Asp382
| <cite>Huang2012</cite>
|-
| [[GH123]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5fr0 5fr0]
| exo-β-N-acetyl-galactosaminidase
| ''Clostridium perfringens''
| ''N''-difluoroacetyl-{{Smallcaps|d}}-galactosamine
| '''Glu345'''
| internal
| <cite>Noach2016</cite>
|-
| [[GH125]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5m7y 5m7y]
| exo-α-1,6-mannosidase
| ''Clostridium perfringens''
| 1,6-α-mannotriose
| '''Asp220'''
| Glu393
| <cite>Alonso-Gil2016</cite>
|-
| [[GH127]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3wrg 3wrg]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bifidobacterium longum''
| {{Smallcaps|l}}-arabinose
| '''Glu322'''
| Cys417
| <cite>Huang2014</cite>
|-
| [[GH128]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH1''
|
|
|
|
|
|
|-
| [[GH130]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5b0s 5b0s]
| β-1,2-mannobiose phosphorylase
| ''Listeria innocua''
| β-1,2-mannotriose
| '''Asp141''' relay
| phosphate
| <cite>Tsuda2015</cite>
|-
| [[GH134]]
| none
| β + α
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5jug 5jug]
| β-mannanase
| ''Streptomyces sp.''
| mannopentaose
| '''Glu45'''
| Asp57
| <cite>Jin2016</cite>
|-
| [[GH136]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}5gqf 5gqf]
| lacto-N-biosidase
| ''Bifidobacterium longum''
| lacto-N-biose
| '''Asp411'''
| Asp418
| <cite>Yamada2017</cite>
|-
| [[GH137]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|l}}
| unknown
| '''''anti'''''
| [{{PDBlink}}5mui 5mui]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0996
| ''Bacteroides thetaiotaomicron''
| pectin oligosaccharide
| '''Glu240'''
| Glu159
| <cite>Ndeh2017</cite>

|-
| [[GH138]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}6hzg 6hzg]
| α-1,2-{{Smallcaps|d}}-galacturonidase
| ''Bacteroides paurosaccharolyticus''
| alpha-{{Smallcaps|d}}-galactopyranuronic
| '''Glu294'''
| Glu361
| <cite>Labourel2019</cite>
|-
| [[GH146]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5opj 5opj]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0349
| ''Bacteroides thetaiotaomicron''
| {{Smallcaps|l}}-arabinose
| '''Glu320'''
| Cys416
| <cite>Luis2018</cite>
|-
| [[GH147]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH148]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH149]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH157]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH158]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH161]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH162]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}6imw 6imw]
| endo-β-1,2-glucanase
| ''Talaromyces funiculosus''
| beta-1,2-glucan
| '''Glu262''' via C3-OH of glc at subs. +2
| Asp446
| <cite>Tanaka2019</cite>
|-
| [http://www.cazy.org/GH0.html n.c.*]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2vjj 2vjj]
| endo-α-N-acetylglucosaminidase
| Bacteriophage HK620
| O18A1 O-antigen hexasaccharide
| '''Asp339'''
| Glu372
| <cite>Barbirz2008</cite>
|}
<nowiki>*</nowiki> n.c.: Found among the collection of [http://www.cazy.org/GH0.html non-classified GH sequences in the CAZy Database].

== References ==

<biblio>
# HeightmanVasella1999 Heightman TD and Vasella AT. ''Recent Insights into Inhibition, Structure, and Mechanism of Configuration-Retaining Glycosidases.'' Angew Chem Int Ed. 1999 38(6):750-770. [http://www3.interscience.wiley.com/journal/55000581/abstract Article online].
# Nerinckx2005 pmid=15642336
# Wu2012 pmid=23137336
# Perez1978 Pérez S and Marchessault RH. ''The exo-anomeric effect: experimental evidence from crystal structures.'' Carbohydr res. 1978 65:114-120. [http://dx.doi.org/10.1016/S0008-6215(00)84218-4 DOI:10.1016/S0008-6215(00)84218-4]
# Cramer1997 Cramer CJ, Truhlar DG, and French AD. ''Exo-anomeric effects on energies and geometries of different conformations of glucose and related systems in the gas phase and aqueous solution.'' Carbohydr res. 1997 298:1-14. [http://dx.doi.org/10.1016/S0008-6215(96)00297-2 DOI:10.1016/S0008-6215(96)00297-2]
# Johnson2009 pmid=19733839
# Alonso2016 pmid=26889578
# Gloster2006 pmid=17002288
# van_Bueren2009 pmid=18976664
# Hrmova2001 pmid=11709165

# Rajan2004 pmid=15341727
# Varrot2003 pmid=12595701
# Zhou1999 pmid=10508787
# Sulzenbacher1999 pmid=10200171
# Urbanikova2011 pmid=21501386
# Guerin2002 pmid=11884144
# Schubot2004 pmid=14756552
# Suzuki2009 pmid=19279191
# Wan2014 pmid=24419374
# Sandgren2004 pmid=15364577
# Uitdehaag1999 pmid=10331869
# Miyake2003 pmid=12741813
# Harris1993 pmid=8431441
# Allouch2004 pmid=15062085
# Wojtkowiak2013 pmid=23275163
# Papanikolau2001 pmid=11560481
# Prag2000 pmid=10884356
# Vocadlo2001 pmid=11518970
# Karlsen1996 pmid=15299731
# Baldwin1993 pmid=8259514
# Cartmell2008 pmid=18799462
# Fernandez-Leiro2010 pmid=20592022
# Abbott2007 pmid=17397864
# Sakurama2012 pmid=22451675
# Sim2008 pmid=18036614
# Verhaest2007 pmid=17335500
# Amaya2004 pmid=15130470
# Zhu2012 pmid=23015718
# Maksimainen2011 pmid=21130883
# Merceron2012 pmid=23012371
# Gibson2007 pmid=17455176
# Shah2008 pmid=18599462
# Czjzek2005 pmid=16212978
# Godoy2016 pmid=27685756
# Fujimoto2010 pmid=20739278
# Kitago2007 pmid=17905739
# Davies1996 pmid=15299721
# Lyu2014 pmid=24766439
# Karaveg2005 pmid=15713668
# Nerinckx2008 pmid=18619586
# Pluvinage2013 pmid=23921382

# Yuan2005 pmid=15893670
# Hoevel2003 pmid=14517232
# Espina2014 pmid=24816105
# Le_Nours2009 pmid=19089956
# Miyanaga2004 pmid=15292273
# Bianchetti2015 pmid=25752603
# Markovic-Housley2000 pmid=11080624
# Imamura2003 pmid=12618437
# Hill2013 pmid=24297913

# Maehara2014 pmid=24482228

# Miyazaki2016 pmid=27688023
# Touhara2014 pmid=24828502
# Suzuki2016 pmid=26494689
# Golan2004 pmid=14573597
# Meng2003 pmid=14517548
# Ito2011 pmid=21354427
# Hurtado-Gerrero2009 pmid=19097997
# Yaoi2007 pmid=17498741
# Thompson2015 pmid=25772148
# Barends2007 pmid=17420245
# Fujimoto2013 pmid=23486481
# Wu2015 pmid=26575439
# Pluvinage2017 pmid=28781080
# Dennis2006 pmid=16565725
# Abbott2009 pmid=19181667
# Hehemann_1_2012 pmid=23150581
# Ficko-Blean2008 pmid=18443291
# Zhu2009 pmid=20081828
# Sogabe2011 pmid=21543843
# Nam2015 pmid=26041776
# Nagae2007 pmid=17459873
# Kitamura2008 pmid=18981178
# Higgins2009 pmid=19608744
# van_Straaten2007 pmid=17502382
# van_Asselt2000 pmid=10684641
# Ndeh2017 pmid=28329766
# Labourel2019 pmid=30877196
# Luis2018 pmid=29255254
# Jin2016 Jin Y, Petricevic M, John A, Raich L, Jenkins H, Portela De Souza L, Cuskin F, Gilbert HJ, Rovira C, Goddard-Borger ED, Williams SJ, and Davies GJ. ''A β-Mannanase with a Lysozyme-like Fold and a Novel Molecular Catalytic Mechanism.'' ACS Cent Sci. 2016 Nov [http://dx.doi.org/10.1021/acscentsci.6b00232 DOI:10.1021/acscentsci.6b00232]
# Yamada2017 pmid=28392148
# Ohnuma2014 pmid=24582745
# Thompson2012 pmid=22219371
# Xie2016 pmid=27777307
# Williams2014 pmid=24339341
# Hehemann_2_2012 pmid=22393053
# Huang2012 pmid=22992047
# Noach2016 pmid=27038508
# Alonso-Gil2016 pmid=28026180
# Huang2014 Huang CH, Zhu Z, Cheng YS, Chan HC, Ko TP, Chen CC, Wang I, Ho MR, Hsu ST, Zeng YF, Huang YN, Liu JR, Guo RT. ''Structure and Catalytic Mechanism of a Glycoside Hydrolase Family-127 β-L-Arabinofuranosidase (HypBA1).'' J Bioprocess Biotech. 2014 4:171 [http://dx.doi.org/10.4172/2155-9821.1000171 DOI:10.4172/2155-9821.1000171]
# Tsuda2015 pmid=26632508
# Barbirz2008 pmid=18547389
# Tanaka2019 pmid=30926603

</biblio>

[[Category:Definitions and explanations]]

Syn/anti lateral protonation

2019-07-31T09:03:21Z

Wim Nerinckx:

{{CuratorApproved}}
* [[Author]]: ^^^Wim Nerinckx^^^
* [[Responsible Curator]]: ^^^Spencer Williams^^^

----

== Overview ==

This page provides a table that summarizes the spatial positioning of the catalytic [[general acid]] residue in the active sites of [[glycoside hydrolase]]s, relative to the substrate. The table below updates those found in the seminal paper on this concept by Heightman and Vasella <cite>HeightmanVasella1999</cite>, and a following paper by Nerinckx ''et al.'' <cite>Nerinckx2005</cite>.

== Background ==

The ''"not from above, but from the side"'' concept of semi-lateral glycosidic oxygen [[General_acid/base|protonation]] by [[glycoside hydrolase]]s was introduced by Heightman and Vasella <cite>HeightmanVasella1999</cite>. It was originally only described for [[Anomeric centre (alpha and beta)|beta]]-equatorial [[glycoside hydrolase]]s, but appears to be equally applicable to enzymes acting on an [[Anomeric centre (alpha and beta)|alpha]]-axial glycosidic bond <cite>Nerinckx2005</cite>. When dividing [[Sub-site nomenclature|subsite -1]] into half-spaces by a plane defined by the glycosidic oxygen and C1' and H1' of the –1 glycoside, many ligand-complexed structures reveal that the [[General_acid/base|proton donor]] is positioned either in the ''syn'' half-space (near the ring-oxygen of the –1 glycoside), or in the ''anti'' half-space (on the opposite side of the ring-oxygen). Members of the same GH [[Families|family]] appear to share a common ''syn'' or ''anti'' [[General_acid/base|protonator]] arrangement and further, this specificity appears to be preserved within [[Clans|Clans]] of [[Families|families]]. This page's compilation of [[Sub-site nomenclature|subsite -1]] occupied complexes shows that about 70% of all GH [[Families|families]] are ''anti'' [[General_acid/base|protonators]].

Closer inspection of crystal structures of [[Sub-site nomenclature|–1/+1 subsite]]-spanning substrates, or substrate-analogue ligands, in complex with enzymes reveals a further intriguing corollary <cite>Nerinckx2005 Wu2012</cite>. In substrate-bound complexes with ''anti'' [[General_acid/base|protonating]] GH enzymes, the scissile [[Anomeric centre (alpha and beta)|anomeric bond]] (often studied using the thio-analogue) shows a dihedral angle φ (O5'-C1'-[O,S]x-Cx) that is in the lowest-energy synclinal (gauche) conformation. The rationale for this is that a minus synclinal dihedral angle φ for an equatorial glycosidic bond, or plus synclinal for an axial glycosidic bond <cite>Perez1978</cite>, allows for hyperconjugative overlap of the C1'-O5' antibonding orbital with an antiperiplanar-oriented lone pair orbital lobe of the glycosidic oxygen, thereby creating partial double bond character and stabilization of the glycosidic bond by 4–5 kcal/mol; this ground-state stabilizing phenomenon is known as the ‘exo-anomeric effect’ <cite>Cramer1997 Johnson2009 Alonso2016</cite>. ''Anti'' [[General_acid/base|protonation]] occurs on the glycosidic oxygen’s antiperiplanar lone pair, thereby removing the stabilizing exo-anomeric effect. This suggests that ''anti'' [[General_acid/base|protonation]] is an enzymic approach for lowering the activation barrier leading to the [[Transition state|transition state]] (Figure 1 centre).

''Syn'' [[General_acid/base|protonating]] [[glycoside hydrolase]]s apparently make use of a different approach <cite>Nerinckx2005 Wu2012</cite>. In many [[Sub-site nomenclature|–1/+1 subsite]]-spanning ligand complexes, the dihedral angle φ of the scissile anomeric bond has been rotated away from its lowest-energy synclinal position: clockwise to minus-anticlinal or antiperiplanar for beta-equatorial; counterclockwise to plus-anticlinal or antiperiplanar for alpha-axial [[Anomeric centre (alpha and beta)|anomeric bonds]]. This removes the hyperconjugative overlap and thus also the stabilizing exo-anomeric effect. And because of this rotation, a lone pair of the glycosidic oxygen is directed into the ''syn'' half-space, allowing it to be protonated by the ''syn''-positioned [[General_acid/base|proton donor]] (Figure 1 right).

[[File:Syn_anti.jpg|800px|thumb|center|Figure 1. Newman projections, with the glycosidic oxygen as proximal atom and the anomeric carbon as distal atom, showing ''anti'' (centre) versus ''syn'' (right) semi-lateral [[General_acid/base|protonation]] in beta-equatorial (top) and alpha-axial (bottom) [[glycoside hydrolase]]s. The indicated φ is the dihedral angle for O5'-C1'-O4-C4.]]

== Table of ''syn/anti'' protonation examples ==

This table contains only one example per GH [[Families|family]] of a ligand-complexed protein structure where the ''syn'' or ''anti'' positioning of the [[General_acid/base|proton donor]] can be clearly observed; other examples may be available on a [[Families|family-by-family]] basis. The reader is thus advised to consult the [http://www.cazy.org/fam/acc_GH.html#table CAZy database] for a current, comprehensive list of CAZyme structures. Where available, the selected examples are Michaelis-type complexes with the ligand spanning the [[Sub-site nomenclature|-1/+1 subsites]], since these have an intact glycosidic or thioglycosidic bond, or are ''N''-analogs of the substrate (''e.g.'' acarbose). In some examples, the [[General_acid/base|proton donor]] has been mutated (''e.g.'', to the corresponding amide or to an alanine), and in those cases one may wish to look at a superposition of the given PDB example with the structure of the native enzyme. If a Michaelis-type complex is not yet available, the second and third example choices, respectively, are trapped glycosyl-enzyme [[intermediate]]s and product complexes where [[Sub-site nomenclature|subsite -1]] is occupied.

''Please also be aware that this is a large table with many data. Please contact the page Author or Responsible Curator with corrections.''

=== Table ===
This table can be re-sorted by clicking on the icons in the header (''javascript must be turned on in your browser''). To reset the page to be sorted by GH family, click the ''View'' tab at the very top of the page.

{| {{Prettytable}} class="sortable"
|- valign="top"
! '''Family'''
! '''Clan'''
! '''Structure fold '''
! '''Anomeric specificity'''
! '''Mechanism'''
! '''''Syn/anti'' protonator'''
! '''Example PDB ID'''
! '''Enzyme'''
! '''Organism'''
! '''Ligand'''
! '''General acid'''
! '''Nucleophile or General base'''
! '''Reference'''
|-
| [[GH1]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2cer 2cer]
| β-glycosidase S
| ''Sulfolobus solfataricus'' P2
| phenethyl glucoimidazole
| '''Glu206'''
| Glu387
| <cite>Gloster2006</cite>
|-
| [[GH2]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vzu 2vzu]
| exo-β-glucosaminidase
| ''Amicolatopsis orientalis''
| PNP-β-{{Smallcaps|d}}-glucosamine
| '''Glu469'''
| Glu541
| <cite>van_Bueren2009</cite>
|-
| [[GH3]]
| none
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1iex 1iex]
| exo-1,3-1,4-glucanase
| ''Hordeum vulgare''
| thiocellobiose
| '''Glu491'''
| Asp285
| <cite>Hrmova2001</cite>
|-
| [[GH4]]
| none
| Rossmann + α6/β3 + β3/α4
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1u8x 1u8x]
| 6-P-α-glucosidase
| ''Bacillus subtilis''
| alpha-{{Smallcaps|d}}-glucose-6-phosphate
| '''Asp172'''
| Not applicable
| <cite>Rajan2004</cite>
|-

| [[GH5]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1h2j 1h2j]
| endo-β-1,4-glucanase
| ''Bacillus agaradhaerens''
| 2',4'-DNP-2-F-cellobioside
| '''Glu129'''
| Glu228
| <cite>Varrot2003</cite>
|-
| [[GH6]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1qjw 1qjw]
| cellobiohydrolase 2
| ''Hypocrea jecorina''
| (Glc)2-S-(Glc)2
| '''Asp221'''
| debated
| <cite>Zhou1999</cite>
|-
| [[GH7]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1ovw 1ovw]
| endo-1,4-glucanase
| ''Fusarium oxysporum''
| thio-(Glc)5
| '''Glu202'''
| Glu197
| <cite>Sulzenbacher1999</cite>
|-
| [[GH8]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1kwf 1kwf]
| endo-1,4-glucanase
| ''Clostridium thermocellum''
| cellopentaose
| '''Glu95'''
| Asp278
| <cite>Guerin2002</cite>
|-
| [[GH9]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1rq5 1rq5]
| cellobiohydrolase
| ''Clostridium thermocellum''
| cellotetraose
| '''Glu795'''
| Asp383
| <cite>Schubot2004</cite>
|-
| [[GH10]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2d24 2d24]
| β-1,4-xylanase
| ''Streptomyces olivaceoviridis'' E-86
| xylopentaose
| '''Glu128'''
| Glu236
| <cite>Suzuki2009</cite>
|-
| [[GH11]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}4hk8 4hk8]
| endo-β-1,4-xylanase
| ''Hypocrea jecorina''
| xylohexaose
| '''Glu177'''
| Glu86
| <cite>Wan2014</cite>
|-
| [[GH12]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1w2u 1w2u]
| endoglucanase
| ''Humicola grisea''
| thiocellotetraose
| '''Glu205'''
| Glu120
| <cite>Sandgren2004</cite>
|-
| [[GH13]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1cxk 1cxk]
| β-cyclodextrin glucanotransferase
| ''Bacillus circulans''
| maltononaose
| '''Glu257'''
| Asp229
| <cite>Uitdehaag1999</cite>
|-
| [[GH14]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1itc 1itc]
| β-amylase
| ''Bacillus cereus''
| maltopentaose
| '''Glu172'''
| Glu367
| <cite>Miyake2003</cite>
|-
| [[GH15]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1dog 1dog]
| glucoamylase
| ''Aspergillus awamori''
| 1-deoxynojirimycin
| '''Glu179'''
| Glu400
| <cite>Harris1993</cite>
|-
| [[GH16]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1urx 1urx]
| β-agarase A
| ''Zobellia galactanivorans''
| oligoagarose
| '''Glu152'''
| Glu147
| <cite>Allouch2004</cite>
|-
| [[GH17]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzj 4gzj]
| endo-β-1,3-glucanase
| ''Solanum tuberosum''
| laminaratriose + laminarabiose
| '''Glu118'''
| Glu259
| <cite>Wojtkowiak2013</cite>
|-
| [[GH18]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1ffr 1ffr]
| chitinase A
| ''Serratia marcescens''
| (NAG)6
| '''Glu315'''
| internal
| <cite>Papanikolau2001</cite>
|-
| [[GH19]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}3wh1 3wh1]
| chitinase
| ''Bryum coronatum''
| (GlcNAc)4
| '''Glu61'''
| Glu70
| <cite>Ohnuma2014</cite>
|-
| [[GH20]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1c7s 1c7s]
| chitobiase
| ''Serratia marcescens''
| chitobiose
| '''Glu540'''
| internal
| <cite>Prag2000</cite>
|-
| [[GH22]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1h6m 1h6m]
| lysozyme C
| ''Gallus gallus''
| Chit-2-F-chitosyl
| '''Glu35'''
| Asp52
| <cite>Vocadlo2001</cite>
|-
| [[GH23]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1lsp 1lsp]
| lysozyme G
| ''Cygnus atratus''
| Bulgecin A
| '''Glu73'''
| internal
| <cite>Karlsen1996</cite>
|-
| [[GH24]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}148l 148l]
| lysozyme E
| Bacteriophage T4
| chitobiosyl
| '''Glu11'''
| Glu26
| <cite>Baldwin1993</cite>
|-
| [[GH26]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vx6 2vx6]
| exo-β-mannanase
| ''Cellvibrio japonicus'' Ueda107
| Gal1Man4
| '''Glu221'''
| Glu338
| <cite>Cartmell2008</cite>
|-
| [[GH27]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}} / beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3lrm 3lrm]
| α-galactosidase
| ''Saccharomyces cerevisiae''
| raffinose
| '''Asp209'''
| Asp141
| <cite>Fernandez-Leiro2010</cite>
|-
| [[GH28]]
| N
| β-helix
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}2uvf 2uvf]
| exo-polygalacturonosidase
| ''Yersinia enterocolitica'' ATCC9610D
| digalacturonic acid
| '''Asp402'''
| Asp381 Asp403
| <cite>Abbott2007</cite>
|-
| [[GH29]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| '''''syn'''''
| [{{PDBlink}}3uet 3uet]
| α-1,3/4-fucosidase
| ''Bifidobacterium longum'' subsp. infantis
| lacto-''N''-fucopentaose II
| '''Glu217'''
| Asp172
| <cite>Sakurama2012</cite>
|-
| [[GH30]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2y24 2y24]
| glucurono-xylanase
| ''Dickea chrysanthemi'' D1
| glucuronoxylan tetrasaccharide
| '''Glu163'''
| Glu253
| <cite>Urbanikova2011</cite>
|-
| [[GH31]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2qmj 2qmj]
| maltase-glucoamylase
| ''Homo sapiens''
| acarbose
| '''Asp542'''
| Asp443
| <cite>Sim2008</cite>
|-
| [[GH32]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2add 2add]
| fructan β-(2,1)-fructosidase
| ''Cichorium intybus''
| sucrose
| '''Glu201'''
| Asp22
| <cite>Verhaest2007</cite>
|-
| [[GH33]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1s0i 1s0i]
| transsialidase
| ''Trypanosoma cruzi''
| sialyllactose
| '''Asp59'''
| Tyr342
| <cite>Amaya2004</cite>
|-
| [[GH34]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzw 4gzw]
| N2 neuraminidase
| ''Influenza'' A Tanzania/205/2010 H3N2
| α-{{Smallcaps|d}}-Neup5Ac-(2,3)-β-{{Smallcaps|d}}-Galp-(1,4)-β-{{Smallcaps|d}}-GlcpNAc
| '''Asp151'''
| Tyr406
| <cite>Zhu2012</cite>
|-
| [[GH35]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3ogv 3ogv]
| β-galactosidase
| ''Hypocrea jecorina''
| 2-phenylethyl 1-thio-β-{{Smallcaps|d}}-galactopyranoside
| '''Glu200'''
| Glu298
| <cite>Maksimainen2011</cite>
|-
| [[GH36]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4fns 4fns]
| β-galactosidase
| ''Geobacillus stearothermophilus''
| 1-deoxy galactonojirimycin
| '''Asp584'''
| Asp478
| <cite>Merceron2012</cite>
|-
| [[GH37]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2jf4 2jf4]
| trehalase
| ''Escherichia coli''
| validoxylamine
| '''Asp312'''
| Glu496
| <cite>Gibson2007</cite>
|-
| [[GH38]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3czn 3czn]
| Golgi α-mannosidase II
| ''Drosophila melanogaster''
| GlcNAcMan(5)GlcNAc(2)
| '''Asp341'''
| Asp204
| <cite>Shah2008</cite>
|-
| [[GH39]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2bfg 2bfg]
| β-xylosidase
| ''Geobacillus stearothermophilus''
| 2,5-dinitrophenyl-β-{{Smallcaps|d}}-xyloside
| '''Glu160'''
| Glu278
| <cite>Czjzek2005</cite>
|-
| [[GH42]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ucf 4ucf]
| β-galactosidase
| ''Bifidobacterium bifidum''
| {{Smallcaps|d}}-galactose
| '''Glu161'''
| Glu320
| <cite>Godoy2016</cite>
|-
| [[GH43]]
| F
| 5-fold β-propeller
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3akh 3akh]
| exo-1,5-α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces avermitilis''
| α-1,5-arabinofuranotriose
| '''Glu196'''
| Asp220
| <cite>Fujimoto2010</cite>
|-
| [[GH44]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2eqd 2eqd]
| endoglucanase
| ''Clostridium thermocellum''
| cellooctaose
| '''Glu186'''
| Glu359
| <cite>Kitago2007</cite>
|-
| [[GH45]]
| none
| 6-stranded β-barrel
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4eng 4eng]
| endo-1,4-glucanase
| ''Humicola insolens''
| cellohexaose
| '''Asp121'''
| Asp10
| <cite>Davies1996</cite>
|-
| [[GH46]]
| I
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4olt 4olt]
| chitosanase
| ''Microbacterium sp.'' OU01
| hexa-glucosamine
| '''Glu25'''
| Asp43
| <cite>Lyu2014</cite>
|-
| [[GH47]]
| none
| (α/α)7
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1x9d 1x9d]
| α-mannosidase I
| ''Homo sapiens''
| Me-2-S-(α-Man)-2-thio-α-Man
| '''Asp463'''
| Glu599
| <cite>Karaveg2005</cite>, <cite>Nerinckx2008</cite>
|-
| [[GH48]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH8''
|
|
|
|
|
|
|-
| [[GH49]]
| N
| β-helix
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH28''
|
|
|
|
|
|
|-
| [[GH50]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4bq5 4bq5]
| exo-β-agarase
| ''Saccharophagus degradans''
| neoagarotetraose
| '''Glu535'''
| Glu695
| <cite>Pluvinage2013</cite>
|-
| [[GH51]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1qw9 1qw9]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Geobacillus stearothermophilus''
| PNP-{{Smallcaps|l}}-arabinofuranoside
| '''Glu175'''
| Glu294
| <cite>Hoevel2003</cite>
|-
| [[GH52]]
| O
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4c1p 4c1p]
| β-xylosidase
| ''Geobacillus thermoglucosidasius''
| xylobiose
| '''Asp517'''
| Glu537
| <cite>Espina2014</cite>
|-
| [[GH53]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2ccr 2ccr]
| β-1,4-galactanase
| ''Bacillus licheniformis''
| galactotriose
| '''Glu165'''
| Glu263
| <cite>Le_Nours2009</cite>
|-
| [[GH54]]
| none
| β-sandwich
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1wd4 1wd4]
| α-{{Smallcaps|l}}-arabinofuranosidase B
| ''Aspergillus kawachii''
| {{Smallcaps|l}}-arabinofuranose
| '''Asp297'''
| Glu221
| <cite>Miyanaga2004</cite>
|-
| [[GH55]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4tz5 4tz5]
| exo-β-1,3-glucanase
| ''Streptomyces sp.'' SirexAA-E
| laminarihexaose
| '''Glu502'''
| unknown
| <cite>Bianchetti2015</cite>
|-
| [[GH56]]
| none
| (β/α)7
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1fcv 1fcv]
| hyaluronidase
| ''Apis mellifera''
| (hyaluron.)4
| '''Glu113'''
| internal
| <cite>Markovic-Housley2000</cite>
|-
| [[GH57]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1k1y 1k1y]
| glucanotransferase
| ''Thermococcus litoralis''
| acarbose
| '''Asp214'''
| Glu123
| <cite>Imamura2003</cite>
|-
| [[GH59]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ccc 4ccc]
| β-galactocerebrosidase
| ''Mus musculus''
| PNP-β-{{Smallcaps|d}}-galactoside
| '''Glu182'''
| Glu258
| <cite>Hill2013</cite>
|-
| [[GH62]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3wn0 3wn0]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces coelicolor''
| β-{{Smallcaps|l}}-Arabinofuranose
| '''Glu361'''
| Asp202
| <cite>Maehara2014</cite>
|-
| [[GH63]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5ca3 5ca3]
| α-glucosidase
| ''Escherichia coli''
| glucose and lactose
| '''Asp501'''
| Glu727
| <cite>Miyazaki2016</cite>
|-
| [[GH65]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}4ktr 4ktr]
| 2-O-α-glucosylglycerol phosphorylase
| ''Bacillus selenitireducens''
| isofagomine
| '''Glu475'''
| phosphate
| <cite>Touhara2014</cite>
|-
| [[GH66]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5axh 5axh]
| dextranase
| ''Thermoanaerobacter pseudethanolicus''
| isomaltohexaose
| '''Glu374'''
| Asp312
| <cite>Suzuki2016</cite>
|-
| [[GH67]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1l8n 1l8n]
| α-glucuronidase
| ''Geobacillus stearothermophilus''
| 4-O-methyl-{{Smallcaps|d}}-glucuronic acid and xylotriose
| '''Glu286'''
| Asp364 Glu392
| <cite>Golan2004</cite>
|-
| [[GH68]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1pt2 1pt2]
| levansucrase
| ''Bacillus subtilis''
| sucrose
| '''Glu342'''
| Asp86
| <cite>Meng2003</cite>
|-
| [[GH70]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3aic 3aic]
| glucansucrase
| ''Streptococcus mutans''
| α-acarbose
| '''Glu515'''
| Asp477
| <cite>Ito2011</cite>
|-
| [[GH72]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w62 2w62]
| β-1,3-glucanotransferase
| ''Saccharomyces cerevisiae'' S288C
| laminaripentaose
| '''Glu176'''
| Glu275
| <cite>Hurtado-Gerrero2009</cite>
|-
| [[GH74]]
| none
| 7-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}2ebs 2ebs]
| cellobiohydrolase (OXG-RCBH)
| ''Geotrichum sp.'' m128
| xyloglucan heptasaccharide
| '''Asp465'''
| Asp35
| <cite>Yaoi2007</cite>
|-
| [[GH76]]
| none
| (α/α)6
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5agd 5agd]
| endo-α-1,6-mannanase
| ''Bacillus circulans''
| α-1,6-mannopentaose
| '''Asp125'''
| Asp124
| <cite>Thompson2015</cite>
|-
| [[GH77]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2oww 2oww]
| 4-α-glucanotransferase
| ''Thermus thermofilus''
| acarbose + 4-deoxy-α-{{Smallcaps|d}}-glucose
| '''Glu340'''
| Asp293
| <cite>Barends2007</cite>
|-
| [[GH78]]
| H
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3w5n 3w5n]
| α-{{Smallcaps|l}}-rhamnosidase
| ''Streptomyces avermitilis''
| {{Smallcaps|l}}-rhamnose
| '''Glu636'''
| Glu895
| <cite>Fujimoto2013</cite>
|-
| [[GH79]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5e9c 5e9c]
| heparanase
| ''Homo sapiens''
| heparin tetrasaccharide
| '''Glu225'''
| Glu343
| <cite>Wu2015</cite>
|-
| [[GH80]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH24''
|
|
|
|
|
|
|-
| [[GH81]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5t4g 5t4g]
| endo-β-1,3-glucanase
| ''Bacillus halodurans'' C-125
| laminarin
| '''Asp466'''
| Glu542
| <cite>Pluvinage2017</cite>
|-
| [[GH83]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1z4x 1z4x]
| hemagglutinin-neuraminidase
| Simian virus 5
| α-2,3-sialyllactose
| '''Glu247''' relay
| Tyr523
| <cite>Yuan2005</cite>
|-
| [[GH84]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2chn 2chn]
| β-''N''-acetyl-glucosaminidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| NAG-thiazoline
| '''Glu242'''
| internal
| <cite>Dennis2006</cite>
|-
| [[GH85]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w92 2w92]
| endo-β-''N''-acetyl-glucosaminidase D
| ''Streptococcus pneumoniae'' TIGR4
| NAG-thiazoline
| '''Glu337'''
| internal
| <cite>Abbott2009</cite>
|-
| [[GH86]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4aw7 4aw7]
| β-porphyranase
| ''Bacteroides plebeius''
| porphyran fragment
| '''Glu152'''
| Glu279
| <cite>Hehemann_1_2012</cite>
|-
| [[GH89]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vcb 2vcb]
| α-''N''-acetyl-glucosaminidase
| ''Clostridium perfringens''
| PUGNAc
| '''Glu483'''
| Glu601
| <cite>Ficko-Blean2008</cite>
|-
| [[GH92]]
| none
| (α/α)6 and β-sandwich
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ww1 2ww1]
| α-1,2-mannosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| thiomannobioside
| '''Glu533'''
| Asp644 Asp642
| <cite>Zhu2009</cite>
|-
| [[GH93]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3a72 3a72]
| exo-arabinanase
| ''Penicillium chrysogenum''
| arabinobiose
| '''Glu246'''
| Glu174
| <cite>Sogabe2011</cite>
|-
| [[GH94]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4zli 4zli]
| cellobionic acid phosphorylase
| ''Saccharophagus degradans''
| 3-O-β-{{Smallcaps|d}}-glucopyranosyl-α-{{Smallcaps|d}}-glucopyranuronic acid
| '''Asp472'''
| phosphate
| <cite>Nam2015</cite>
|-
| [[GH95]]
| none
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ead 2ead]
| α-1,2-{{Smallcaps|l}}-fucosidase
| ''Bifidobacterium bifidum''
| Fuc-α-1,2-Gal
| '''Glu566'''
| Asn423 Asp766
| <cite>Nagae2007</cite>
|-
| [[GH97]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining + inverting
| '''''anti'''''
| [{{PDBlink}}2zq0 2zq0]
| α-glucosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| acarbose
| '''Glu532'''
| Glu508
| <cite>Kitamura2008</cite>
|-
| [[GH98]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2wmg 2wmg]
| endo-β-1,4-galactosidase
| ''Streptococcus pneumoniae''
| A-LewisY pentasaccharide
| '''Glu158'''
| Asp251 Glu301
| <cite>Higgins2009</cite>
|-
| [[GH99]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ad4 4ad4]
| endo-α-mannosidase
| ''Bacteroides xylanisolvens''
| glucose-1,3-isofagomine and α-1,2- mannobiose
| '''Glu336'''
| debated
| <cite>Thompson2012</cite>
|-
| [[GH100]]
| none
| (α/α)6 core
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5gop 5gop]
| invertase
| ''Anabaena (Nostoc) sp.'' pcc7120
| sucrose
| '''Asp188'''
| Glu414
| <cite>Xie2016</cite>
|-
| [[GH102]]
| none
| double-ψ β-barrel
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}2pi8 2pi8]
| lytic transglycosylase A
| ''Escherichia coli''
| chitohexaose
| '''Asp308'''
| none
| <cite>van_Straaten2007</cite>
|-
| [[GH103]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1d0k 1d0k]
| lytic transglycosylase SLT35
| ''Escherichia coli''
| murodipeptides
| '''Glu162'''
| internal
| <cite>van_Asselt2000</cite>
|-
| [[GH106]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5mwk 5mwk]
| α-{{Smallcaps|l}}-rhamnosidase BT_0986
| ''Bacteroides thetaiotaomicron''
| pectin heptasaccharide
| '''Glu461'''
| Glu593 or Glu561
| <cite>Ndeh2017</cite>
|-
| [[GH107]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| ''predicted syn by clan''
| ''see at GH29''
|
|
|
|
|
|
|-
| [[GH113]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4cd8 4cd8]
| β-mannanase
| ''Alicyclobacillus acidocaldarius''
| mannobioimidazole
| '''Glu151'''
| Glu231
| <cite>Williams2014</cite>
|-
| [[GH116]]
| O
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at GH52''
|
|
|
|
|
|
|-
| [[GH117]]
| none
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}4ak7 4ak7]
| α-1,3-3,6-anhydro-{{Smallcaps|l}}-galactosidase
| ''Bacteroides plebeius''
| neoagarobiose
| '''His302'''
| Asp90
| <cite>Hehemann_2_2012</cite>
|-
| [[GH120]]
| none
| parallel β-helix and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3vsv 3vsv]
| β-xylosidase XylC
| ''Thermoanaerobacterium saccharolyticum'' JW/SL-YS485
| {{Smallcaps|d}}-xylose
| '''Glu405'''
| Asp382
| <cite>Huang2012</cite>
|-
| [[GH123]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5fr0 5fr0]
| exo-β-N-acetyl-galactosaminidase
| ''Clostridium perfringens''
| ''N''-difluoroacetyl-{{Smallcaps|d}}-galactosamine
| '''Glu345'''
| internal
| <cite>Noach2016</cite>
|-
| [[GH125]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5m7y 5m7y]
| exo-α-1,6-mannosidase
| ''Clostridium perfringens''
| 1,6-α-mannotriose
| '''Asp220'''
| Glu393
| <cite>Alonso-Gil2016</cite>
|-
| [[GH127]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3wrg 3wrg]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bifidobacterium longum''
| {{Smallcaps|l}}-arabinose
| '''Glu322'''
| Cys417
| <cite>Huang2014</cite>
|-
| [[GH128]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH1''
|
|
|
|
|
|
|-
| [[GH130]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5b0s 5b0s]
| β-1,2-mannobiose phosphorylase
| ''Listeria innocua''
| β-1,2-mannotriose
| '''Asp141''' relay
| phosphate
| <cite>Tsuda2015</cite>
|-
| [[GH134]]
| none
| β + α
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5jug 5jug]
| β-mannanase
| ''Streptomyces sp.''
| mannopentaose
| '''Glu45'''
| Asp57
| <cite>Jin2016</cite>
|-
| [[GH136]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}5gqf 5gqf]
| lacto-N-biosidase
| ''Bifidobacterium longum''
| lacto-N-biose
| '''Asp411'''
| Asp418
| <cite>Yamada2017</cite>
|-
| [[GH137]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|l}}
| unknown
| '''''anti'''''
| [{{PDBlink}}5mui 5mui]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0996
| ''Bacteroides thetaiotaomicron''
| pectin oligosaccharide
| '''Glu240'''
| Glu159
| <cite>Ndeh2017</cite>

|-
| [[GH138]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}6hzg 6hzg]
| α-1,2-{{Smallcaps|d}}-galacturonidase
| ''Bacteroides paurosaccharolyticus''
| alpha-{{Smallcaps|d}}-galactopyranuronic
| '''Glu294'''
| Glu361
| <cite>Labourel2019</cite>
|-
| [[GH146]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5opj 5opj]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0349
| ''Bacteroides thetaiotaomicron''
| {{Smallcaps|l}}-arabinose
| '''Glu320'''
| Cys416
| <cite>Luis2018</cite>
|-
| [[GH147]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH148]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH149]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH157]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH158]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH161]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH162]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}6imw 6imw]
| endo-β-1,2-glucanase
| ''Talaromyces funiculosus''
| beta-1,2-glucan
| '''Glu262''' via C3-OH of glc at subs. +2
| Asp446
| <cite>Tanaka2019</cite>
|-
| [http://www.cazy.org/GH0.html n.c.*]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2vjj 2vjj]
| endo-α-N-acetylglucosaminidase
| Bacteriophage HK620
| O18A1 O-antigen hexasaccharide
| '''Asp339'''
| Glu372
| <cite>Barbirz2008</cite>
|}
<nowiki>*</nowiki> n.c.: Found among the collection of [http://www.cazy.org/GH0.html non-classified GH sequences in the CAZy Database].

== References ==

<biblio>
# HeightmanVasella1999 Heightman TD and Vasella AT. ''Recent Insights into Inhibition, Structure, and Mechanism of Configuration-Retaining Glycosidases.'' Angew Chem Int Ed. 1999 38(6):750-770. [http://www3.interscience.wiley.com/journal/55000581/abstract Article online].
# Nerinckx2005 pmid=15642336
# Wu2012 pmid=23137336
# Perez1978 Pérez S and Marchessault RH. ''The exo-anomeric effect: experimental evidence from crystal structures.'' Carbohydr res. 1978 65:114-120. [http://dx.doi.org/10.1016/S0008-6215(00)84218-4 DOI:10.1016/S0008-6215(00)84218-4]
# Cramer1997 Cramer CJ, Truhlar DG, and French AD. ''Exo-anomeric effects on energies and geometries of different conformations of glucose and related systems in the gas phase and aqueous solution.'' Carbohydr res. 1997 298:1-14. [http://dx.doi.org/10.1016/S0008-6215(96)00297-2 DOI:10.1016/S0008-6215(96)00297-2]
# Johnson2009 pmid=19733839
# Alonso2016 pmid=26889578
# Gloster2006 pmid=17002288
# van_Bueren2009 pmid=18976664
# Hrmova2001 pmid=11709165

# Rajan2004 pmid=15341727
# Varrot2003 pmid=12595701
# Zhou1999 pmid=10508787
# Sulzenbacher1999 pmid=10200171
# Urbanikova2011 pmid=21501386
# Guerin2002 pmid=11884144
# Schubot2004 pmid=14756552
# Suzuki2009 pmid=19279191
# Wan2014 pmid=24419374
# Sandgren2004 pmid=15364577
# Uitdehaag1999 pmid=10331869
# Miyake2003 pmid=12741813
# Harris1993 pmid=8431441
# Allouch2004 pmid=15062085
# Wojtkowiak2013 pmid=23275163
# Papanikolau2001 pmid=11560481
# Prag2000 pmid=10884356
# Vocadlo2001 pmid=11518970
# Karlsen1996 pmid=15299731
# Baldwin1993 pmid=8259514
# Cartmell2008 pmid=18799462
# Fernandez-Leiro2010 pmid=20592022
# Abbott2007 pmid=17397864
# Sakurama2012 pmid=22451675
# Sim2008 pmid=18036614
# Verhaest2007 pmid=17335500
# Amaya2004 pmid=15130470
# Zhu2012 pmid=23015718
# Maksimainen2011 pmid=21130883
# Merceron2012 pmid=23012371
# Gibson2007 pmid=17455176
# Shah2008 pmid=18599462
# Czjzek2005 pmid=16212978
# Godoy2016 pmid=27685756
# Fujimoto2010 pmid=20739278
# Kitago2007 pmid=17905739
# Davies1996 pmid=15299721
# Lyu2014 pmid=24766439
# Karaveg2005 pmid=15713668
# Nerinckx2008 pmid=18619586
# Pluvinage2013 pmid=23921382

# Yuan2005 pmid=15893670
# Hoevel2003 pmid=14517232
# Espina2014 pmid=24816105
# Le_Nours2009 pmid=19089956
# Miyanaga2004 pmid=15292273
# Bianchetti2015 pmid=25752603
# Markovic-Housley2000 pmid=11080624
# Imamura2003 pmid=12618437
# Hill2013 pmid=24297913

# Maehara2014 pmid=24482228

# Miyazaki2016 pmid=27688023
# Touhara2014 pmid=24828502
# Suzuki2016 pmid=26494689
# Golan2004 pmid=14573597
# Meng2003 pmid=14517548
# Ito2011 pmid=21354427
# Hurtado-Gerrero2009 pmid=19097997
# Yaoi2007 pmid=17498741
# Thompson2015 pmid=25772148
# Barends2007 pmid=17420245
# Fujimoto2013 pmid=23486481
# Wu2015 pmid=26575439
# Pluvinage2017 pmid=28781080
# Dennis2006 pmid=16565725
# Abbott2009 pmid=19181667
# Hehemann_1_2012 pmid=23150581
# Ficko-Blean2008 pmid=18443291
# Zhu2009 pmid=20081828
# Sogabe2011 pmid=21543843
# Nam2015 pmid=26041776
# Nagae2007 pmid=17459873
# Kitamura2008 pmid=18981178
# Higgins2009 pmid=19608744
# van_Straaten2007 pmid=17502382
# van_Asselt2000 pmid=10684641
# Ndeh2017 pmid=28329766
# Labourel2019 pmid=30877196
# Luis2018 pmid=29255254
# Jin2016 Jin Y, Petricevic M, John A, Raich L, Jenkins H, Portela De Souza L, Cuskin F, Gilbert HJ, Rovira C, Goddard-Borger ED, Williams SJ, and Davies GJ. ''A β-Mannanase with a Lysozyme-like Fold and a Novel Molecular Catalytic Mechanism.'' ACS Cent Sci. 2016 Nov [http://dx.doi.org/10.1021/acscentsci.6b00232 DOI:10.1021/acscentsci.6b00232]
# Yamada2017 pmid=28392148
# Ohnuma2014 pmid=24582745
# Thompson2012 pmid=22219371
# Xie2016 pmid=27777307
# Williams2014 pmid=24339341
# Hehemann_2_2012 pmid=22393053
# Huang2012 pmid=22992047
# Noach2016 pmid=27038508
# Alonso-Gil2016 pmid=28026180
# Huang2014 Huang CH, Zhu Z, Cheng YS, Chan HC, Ko TP, Chen CC, Wang I, Ho MR, Hsu ST, Zeng YF, Huang YN, Liu JR, Guo RT. ''Structure and Catalytic Mechanism of a Glycoside Hydrolase Family-127 β-L-Arabinofuranosidase (HypBA1).'' J Bioprocess Biotech. 2014 4:171 [http://dx.doi.org/10.4172/2155-9821.1000171 DOI:10.4172/2155-9821.1000171]
# Tsuda2015 pmid=26632508
# Barbirz2008 pmid=18547389
# Tanaka2019 pmid=30926603

</biblio>

[[Category:Definitions and explanations]]

Syn/anti lateral protonation

2019-07-31T09:01:33Z

Wim Nerinckx:

{{CuratorApproved}}
* [[Author]]: ^^^Wim Nerinckx^^^
* [[Responsible Curator]]: ^^^Spencer Williams^^^

----

== Overview ==

This page provides a table that summarizes the spatial positioning of the catalytic [[general acid]] residue in the active sites of [[glycoside hydrolase]]s, relative to the substrate. The table below updates those found in the seminal paper on this concept by Heightman and Vasella <cite>HeightmanVasella1999</cite>, and a following paper by Nerinckx ''et al.'' <cite>Nerinckx2005</cite>.

== Background ==

The ''"not from above, but from the side"'' concept of semi-lateral glycosidic oxygen [[General_acid/base|protonation]] by [[glycoside hydrolase]]s was introduced by Heightman and Vasella <cite>HeightmanVasella1999</cite>. It was originally only described for [[Anomeric centre (alpha and beta)|beta]]-equatorial [[glycoside hydrolase]]s, but appears to be equally applicable to enzymes acting on an [[Anomeric centre (alpha and beta)|alpha]]-axial glycosidic bond <cite>Nerinckx2005</cite>. When dividing [[Sub-site nomenclature|subsite -1]] into half-spaces by a plane defined by the glycosidic oxygen and C1' and H1' of the –1 glycoside, many ligand-complexed structures reveal that the [[General_acid/base|proton donor]] is positioned either in the ''syn'' half-space (near the ring-oxygen of the –1 glycoside), or in the ''anti'' half-space (on the opposite side of the ring-oxygen). Members of the same GH [[Families|family]] appear to share a common ''syn'' or ''anti'' [[General_acid/base|protonator]] arrangement and further, this specificity appears to be preserved within [[Clans|Clans]] of [[Families|families]]. This page's compilation of [[Sub-site nomenclature|subsite -1]] occupied complexes shows that about 70% of all GH [[Families|families]] are ''anti'' [[General_acid/base|protonators]].

Closer inspection of crystal structures of [[Sub-site nomenclature|–1/+1 subsite]]-spanning substrates, or substrate-analogue ligands, in complex with enzymes reveals a further intriguing corollary <cite>Nerinckx2005 Wu2012</cite>. In substrate-bound complexes with ''anti'' [[General_acid/base|protonating]] GH enzymes, the scissile [[Anomeric centre (alpha and beta)|anomeric bond]] (often studied using the thio-analogue) shows a dihedral angle φ (O5'-C1'-[O,S]x-Cx) that is in the lowest-energy synclinal (gauche) conformation. The rationale for this is that a minus synclinal dihedral angle φ for an equatorial glycosidic bond, or plus synclinal for an axial glycosidic bond <cite>Perez1978</cite>, allows for hyperconjugative overlap of the C1'-O5' antibonding orbital with an antiperiplanar-oriented lone pair orbital lobe of the glycosidic oxygen, thereby creating partial double bond character and stabilization of the glycosidic bond by 4–5 kcal/mol; this ground-state stabilizing phenomenon is known as the ‘exo-anomeric effect’ <cite>Cramer1997 Johnson2009 Alonso2016</cite>. ''Anti'' [[General_acid/base|protonation]] occurs on the glycosidic oxygen’s antiperiplanar lone pair, thereby removing the stabilizing exo-anomeric effect. This suggests that ''anti'' [[General_acid/base|protonation]] is an enzymic approach for lowering the activation barrier leading to the [[Transition state|transition state]] (Figure 1 centre).

''Syn'' [[General_acid/base|protonating]] [[glycoside hydrolase]]s apparently make use of a different approach <cite>Nerinckx2005 Wu2012</cite>. In many [[Sub-site nomenclature|–1/+1 subsite]]-spanning ligand complexes, the dihedral angle φ of the scissile anomeric bond has been rotated away from its lowest-energy synclinal position: clockwise to minus-anticlinal or antiperiplanar for beta-equatorial; counterclockwise to plus-anticlinal or antiperiplanar for alpha-axial [[Anomeric centre (alpha and beta)|anomeric bonds]]. This removes the hyperconjugative overlap and thus also the stabilizing exo-anomeric effect. And because of this rotation, a lone pair of the glycosidic oxygen is directed into the ''syn'' half-space, allowing it to be protonated by the ''syn''-positioned [[General_acid/base|proton donor]] (Figure 1 right).

[[File:Syn_anti.jpg|800px|thumb|center|Figure 1. Newman projections, with the glycosidic oxygen as proximal atom and the anomeric carbon as distal atom, showing ''anti'' (centre) versus ''syn'' (right) semi-lateral [[General_acid/base|protonation]] in beta-equatorial (top) and alpha-axial (bottom) [[glycoside hydrolase]]s. The indicated φ is the dihedral angle for O5'-C1'-O4-C4.]]

== Table of ''syn/anti'' protonation examples ==

This table contains only one example per GH [[Families|family]] of a ligand-complexed protein structure where the ''syn'' or ''anti'' positioning of the [[General_acid/base|proton donor]] can be clearly observed; other examples may be available on a [[Families|family-by-family]] basis. The reader is thus advised to consult the [http://www.cazy.org/fam/acc_GH.html#table CAZy database] for a current, comprehensive list of CAZyme structures. Where available, the selected examples are Michaelis-type complexes with the ligand spanning the [[Sub-site nomenclature|-1/+1 subsites]], since these have an intact glycosidic or thioglycosidic bond, or are ''N''-analogs of the substrate (''e.g.'' acarbose). In some examples, the [[General_acid/base|proton donor]] has been mutated (''e.g.'', to the corresponding amide or to an alanine), and in those cases one may wish to look at a superposition of the given PDB example with the structure of the native enzyme. If a Michaelis-type complex is not yet available, the second and third example choices, respectively, are trapped glycosyl-enzyme [[intermediate]]s and product complexes where [[Sub-site nomenclature|subsite -1]] is occupied.

''Please also be aware that this is a large table with many data. Please contact the page Author or Responsible Curator with corrections.''

=== Table ===
This table can be re-sorted by clicking on the icons in the header (''javascript must be turned on in your browser''). To reset the page to be sorted by GH family, click the ''View'' tab at the very top of the page.

{| {{Prettytable}} class="sortable"
|- valign="top"
! '''Family'''
! '''Clan'''
! '''Structure fold '''
! '''Anomeric specificity'''
! '''Mechanism'''
! '''''Syn/anti'' protonator'''
! '''Example PDB ID'''
! '''Enzyme'''
! '''Organism'''
! '''Ligand'''
! '''General acid'''
! '''Nucleophile or General base'''
! '''Reference'''
|-
| [[GH1]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2cer 2cer]
| β-glycosidase S
| ''Sulfolobus solfataricus'' P2
| phenethyl glucoimidazole
| '''Glu206'''
| Glu387
| <cite>Gloster2006</cite>
|-
| [[GH2]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vzu 2vzu]
| exo-β-glucosaminidase
| ''Amicolatopsis orientalis''
| PNP-β-{{Smallcaps|d}}-glucosamine
| '''Glu469'''
| Glu541
| <cite>van_Bueren2009</cite>
|-
| [[GH3]]
| none
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1iex 1iex]
| exo-1,3-1,4-glucanase
| ''Hordeum vulgare''
| thiocellobiose
| '''Glu491'''
| Asp285
| <cite>Hrmova2001</cite>
|-
| [[GH4]]
| none
| Rossmann + α6/β3 + β3/α4
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1u8x 1u8x]
| 6-P-α-glucosidase
| ''Bacillus subtilis''
| alpha-{{Smallcaps|d}}-glucose-6-phosphate
| '''Asp172'''
| Not applicable
| <cite>Rajan2004</cite>
|-

| [[GH5]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1h2j 1h2j]
| endo-β-1,4-glucanase
| ''Bacillus agaradhaerens''
| 2',4'-DNP-2-F-cellobioside
| '''Glu129'''
| Glu228
| <cite>Varrot2003</cite>
|-
| [[GH6]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1qjw 1qjw]
| cellobiohydrolase 2
| ''Hypocrea jecorina''
| (Glc)2-S-(Glc)2
| '''Asp221'''
| debated
| <cite>Zhou1999</cite>
|-
| [[GH7]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1ovw 1ovw]
| endo-1,4-glucanase
| ''Fusarium oxysporum''
| thio-(Glc)5
| '''Glu202'''
| Glu197
| <cite>Sulzenbacher1999</cite>
|-
| [[GH8]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1kwf 1kwf]
| endo-1,4-glucanase
| ''Clostridium thermocellum''
| cellopentaose
| '''Glu95'''
| Asp278
| <cite>Guerin2002</cite>
|-
| [[GH9]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1rq5 1rq5]
| cellobiohydrolase
| ''Clostridium thermocellum''
| cellotetraose
| '''Glu795'''
| Asp383
| <cite>Schubot2004</cite>
|-
| [[GH10]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2d24 2d24]
| β-1,4-xylanase
| ''Streptomyces olivaceoviridis'' E-86
| xylopentaose
| '''Glu128'''
| Glu236
| <cite>Suzuki2009</cite>
|-
| [[GH11]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}4hk8 4hk8]
| endo-β-1,4-xylanase
| ''Hypocrea jecorina''
| xylohexaose
| '''Glu177'''
| Glu86
| <cite>Wan2014</cite>
|-
| [[GH12]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1w2u 1w2u]
| endoglucanase
| ''Humicola grisea''
| thiocellotetraose
| '''Glu205'''
| Glu120
| <cite>Sandgren2004</cite>
|-
| [[GH13]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1cxk 1cxk]
| β-cyclodextrin glucanotransferase
| ''Bacillus circulans''
| maltononaose
| '''Glu257'''
| Asp229
| <cite>Uitdehaag1999</cite>
|-
| [[GH14]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1itc 1itc]
| β-amylase
| ''Bacillus cereus''
| maltopentaose
| '''Glu172'''
| Glu367
| <cite>Miyake2003</cite>
|-
| [[GH15]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1dog 1dog]
| glucoamylase
| ''Aspergillus awamori''
| 1-deoxynojirimycin
| '''Glu179'''
| Glu400
| <cite>Harris1993</cite>
|-
| [[GH16]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1urx 1urx]
| β-agarase A
| ''Zobellia galactanivorans''
| oligoagarose
| '''Glu152'''
| Glu147
| <cite>Allouch2004</cite>
|-
| [[GH17]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzj 4gzj]
| endo-β-1,3-glucanase
| ''Solanum tuberosum''
| laminaratriose + laminarabiose
| '''Glu118'''
| Glu259
| <cite>Wojtkowiak2013</cite>
|-
| [[GH18]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1ffr 1ffr]
| chitinase A
| ''Serratia marcescens''
| (NAG)6
| '''Glu315'''
| internal
| <cite>Papanikolau2001</cite>
|-
| [[GH19]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}3wh1 3wh1]
| chitinase
| ''Bryum coronatum''
| (GlcNAc)4
| '''Glu61'''
| Glu70
| <cite>Ohnuma2014</cite>
|-
| [[GH20]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1c7s 1c7s]
| chitobiase
| ''Serratia marcescens''
| chitobiose
| '''Glu540'''
| internal
| <cite>Prag2000</cite>
|-
| [[GH22]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1h6m 1h6m]
| lysozyme C
| ''Gallus gallus''
| Chit-2-F-chitosyl
| '''Glu35'''
| Asp52
| <cite>Vocadlo2001</cite>
|-
| [[GH23]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1lsp 1lsp]
| lysozyme G
| ''Cygnus atratus''
| Bulgecin A
| '''Glu73'''
| internal
| <cite>Karlsen1996</cite>
|-
| [[GH24]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}148l 148l]
| lysozyme E
| Bacteriophage T4
| chitobiosyl
| '''Glu11'''
| Glu26
| <cite>Baldwin1993</cite>
|-
| [[GH26]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vx6 2vx6]
| exo-β-mannanase
| ''Cellvibrio japonicus'' Ueda107
| Gal1Man4
| '''Glu221'''
| Glu338
| <cite>Cartmell2008</cite>
|-
| [[GH27]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}} / beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3lrm 3lrm]
| α-galactosidase
| ''Saccharomyces cerevisiae''
| raffinose
| '''Asp209'''
| Asp141
| <cite>Fernandez-Leiro2010</cite>
|-
| [[GH28]]
| N
| β-helix
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}2uvf 2uvf]
| exo-polygalacturonosidase
| ''Yersinia enterocolitica'' ATCC9610D
| digalacturonic acid
| '''Asp402'''
| Asp381 Asp403
| <cite>Abbott2007</cite>
|-
| [[GH29]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| '''''syn'''''
| [{{PDBlink}}3uet 3uet]
| α-1,3/4-fucosidase
| ''Bifidobacterium longum'' subsp. infantis
| lacto-''N''-fucopentaose II
| '''Glu217'''
| Asp172
| <cite>Sakurama2012</cite>
|-
| [[GH30]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2y24 2y24]
| glucurono-xylanase
| ''Dickea chrysanthemi'' D1
| glucuronoxylan tetrasaccharide
| '''Glu163'''
| Glu253
| <cite>Urbanikova2011</cite>
|-
| [[GH31]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2qmj 2qmj]
| maltase-glucoamylase
| ''Homo sapiens''
| acarbose
| '''Asp542'''
| Asp443
| <cite>Sim2008</cite>
|-
| [[GH32]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2add 2add]
| fructan β-(2,1)-fructosidase
| ''Cichorium intybus''
| sucrose
| '''Glu201'''
| Asp22
| <cite>Verhaest2007</cite>
|-
| [[GH33]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1s0i 1s0i]
| transsialidase
| ''Trypanosoma cruzi''
| sialyllactose
| '''Asp59'''
| Tyr342
| <cite>Amaya2004</cite>
|-
| [[GH34]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzw 4gzw]
| N2 neuraminidase
| ''Influenza'' A Tanzania/205/2010 H3N2
| α-{{Smallcaps|d}}-Neup5Ac-(2,3)-β-{{Smallcaps|d}}-Galp-(1,4)-β-{{Smallcaps|d}}-GlcpNAc
| '''Asp151'''
| Tyr406
| <cite>Zhu2012</cite>
|-
| [[GH35]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3ogv 3ogv]
| β-galactosidase
| ''Hypocrea jecorina''
| 2-phenylethyl 1-thio-β-{{Smallcaps|d}}-galactopyranoside
| '''Glu200'''
| Glu298
| <cite>Maksimainen2011</cite>
|-
| [[GH36]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4fns 4fns]
| β-galactosidase
| ''Geobacillus stearothermophilus''
| 1-deoxy galactonojirimycin
| '''Asp584'''
| Asp478
| <cite>Merceron2012</cite>
|-
| [[GH37]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2jf4 2jf4]
| trehalase
| ''Escherichia coli''
| validoxylamine
| '''Asp312'''
| Glu496
| <cite>Gibson2007</cite>
|-
| [[GH38]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3czn 3czn]
| Golgi α-mannosidase II
| ''Drosophila melanogaster''
| GlcNAcMan(5)GlcNAc(2)
| '''Asp341'''
| Asp204
| <cite>Shah2008</cite>
|-
| [[GH39]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2bfg 2bfg]
| β-xylosidase
| ''Geobacillus stearothermophilus''
| 2,5-dinitrophenyl-β-{{Smallcaps|d}}-xyloside
| '''Glu160'''
| Glu278
| <cite>Czjzek2005</cite>
|-
| [[GH42]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ucf 4ucf]
| β-galactosidase
| ''Bifidobacterium bifidum''
| {{Smallcaps|d}}-galactose
| '''Glu161'''
| Glu320
| <cite>Godoy2016</cite>
|-
| [[GH43]]
| F
| 5-fold β-propeller
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3akh 3akh]
| exo-1,5-α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces avermitilis''
| α-1,5-arabinofuranotriose
| '''Glu196'''
| Asp220
| <cite>Fujimoto2010</cite>
|-
| [[GH44]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2eqd 2eqd]
| endoglucanase
| ''Clostridium thermocellum''
| cellooctaose
| '''Glu186'''
| Glu359
| <cite>Kitago2007</cite>
|-
| [[GH45]]
| none
| 6-stranded β-barrel
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4eng 4eng]
| endo-1,4-glucanase
| ''Humicola insolens''
| cellohexaose
| '''Asp121'''
| Asp10
| <cite>Davies1996</cite>
|-
| [[GH46]]
| I
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4olt 4olt]
| chitosanase
| ''Microbacterium sp.'' OU01
| hexa-glucosamine
| '''Glu25'''
| Asp43
| <cite>Lyu2014</cite>
|-
| [[GH47]]
| none
| (α/α)7
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1x9d 1x9d]
| α-mannosidase I
| ''Homo sapiens''
| Me-2-S-(α-Man)-2-thio-α-Man
| '''Asp463'''
| Glu599
| <cite>Karaveg2005</cite>, <cite>Nerinckx2008</cite>
|-
| [[GH48]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH8''
|
|
|
|
|
|
|-
| [[GH49]]
| N
| β-helix
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH28''
|
|
|
|
|
|
|-
| [[GH50]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4bq5 4bq5]
| exo-β-agarase
| ''Saccharophagus degradans''
| neoagarotetraose
| '''Glu535'''
| Glu695
| <cite>Pluvinage2013</cite>
|-
| [[GH51]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1qw9 1qw9]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Geobacillus stearothermophilus''
| PNP-{{Smallcaps|l}}-arabinofuranoside
| '''Glu175'''
| Glu294
| <cite>Hoevel2003</cite>
|-
| [[GH52]]
| O
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4c1p 4c1p]
| β-xylosidase
| ''Geobacillus thermoglucosidasius''
| xylobiose
| '''Asp517'''
| Glu537
| <cite>Espina2014</cite>
|-
| [[GH53]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2ccr 2ccr]
| β-1,4-galactanase
| ''Bacillus licheniformis''
| galactotriose
| '''Glu165'''
| Glu263
| <cite>Le_Nours2009</cite>
|-
| [[GH54]]
| none
| β-sandwich
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1wd4 1wd4]
| α-{{Smallcaps|l}}-arabinofuranosidase B
| ''Aspergillus kawachii''
| {{Smallcaps|l}}-arabinofuranose
| '''Asp297'''
| Glu221
| <cite>Miyanaga2004</cite>
|-
| [[GH55]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4tz5 4tz5]
| exo-β-1,3-glucanase
| ''Streptomyces sp.'' SirexAA-E
| laminarihexaose
| '''Glu502'''
| unknown
| <cite>Bianchetti2015</cite>
|-
| [[GH56]]
| none
| (β/α)7
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1fcv 1fcv]
| hyaluronidase
| ''Apis mellifera''
| (hyaluron.)4
| '''Glu113'''
| internal
| <cite>Markovic-Housley2000</cite>
|-
| [[GH57]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1k1y 1k1y]
| glucanotransferase
| ''Thermococcus litoralis''
| acarbose
| '''Asp214'''
| Glu123
| <cite>Imamura2003</cite>
|-
| [[GH59]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ccc 4ccc]
| β-galactocerebrosidase
| ''Mus musculus''
| PNP-β-{{Smallcaps|d}}-galactoside
| '''Glu182'''
| Glu258
| <cite>Hill2013</cite>
|-
| [[GH62]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3wn0 3wn0]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces coelicolor''
| β-{{Smallcaps|l}}-Arabinofuranose
| '''Glu361'''
| Asp202
| <cite>Maehara2014</cite>
|-
| [[GH63]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5ca3 5ca3]
| α-glucosidase
| ''Escherichia coli''
| glucose and lactose
| '''Asp501'''
| Glu727
| <cite>Miyazaki2016</cite>
|-
| [[GH65]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}4ktr 4ktr]
| 2-O-α-glucosylglycerol phosphorylase
| ''Bacillus selenitireducens''
| isofagomine
| '''Glu475'''
| phosphate
| <cite>Touhara2014</cite>
|-
| [[GH66]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5axh 5axh]
| dextranase
| ''Thermoanaerobacter pseudethanolicus''
| isomaltohexaose
| '''Glu374'''
| Asp312
| <cite>Suzuki2016</cite>
|-
| [[GH67]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1l8n 1l8n]
| α-glucuronidase
| ''Geobacillus stearothermophilus''
| 4-O-methyl-{{Smallcaps|d}}-glucuronic acid and xylotriose
| '''Glu286'''
| Asp364 Glu392
| <cite>Golan2004</cite>
|-
| [[GH68]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1pt2 1pt2]
| levansucrase
| ''Bacillus subtilis''
| sucrose
| '''Glu342'''
| Asp86
| <cite>Meng2003</cite>
|-
| [[GH70]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3aic 3aic]
| glucansucrase
| ''Streptococcus mutans''
| α-acarbose
| '''Glu515'''
| Asp477
| <cite>Ito2011</cite>
|-
| [[GH72]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w62 2w62]
| β-1,3-glucanotransferase
| ''Saccharomyces cerevisiae'' S288C
| laminaripentaose
| '''Glu176'''
| Glu275
| <cite>Hurtado-Gerrero2009</cite>
|-
| [[GH74]]
| none
| 7-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}2ebs 2ebs]
| cellobiohydrolase (OXG-RCBH)
| ''Geotrichum sp.'' m128
| xyloglucan heptasaccharide
| '''Asp465'''
| Asp35
| <cite>Yaoi2007</cite>
|-
| [[GH76]]
| none
| (α/α)6
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5agd 5agd]
| endo-α-1,6-mannanase
| ''Bacillus circulans''
| α-1,6-mannopentaose
| '''Asp125'''
| Asp124
| <cite>Thompson2015</cite>
|-
| [[GH77]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2oww 2oww]
| 4-α-glucanotransferase
| ''Thermus thermofilus''
| acarbose + 4-deoxy-α-{{Smallcaps|d}}-glucose
| '''Glu340'''
| Asp293
| <cite>Barends2007</cite>
|-
| [[GH78]]
| H
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3w5n 3w5n]
| α-{{Smallcaps|l}}-rhamnosidase
| ''Streptomyces avermitilis''
| {{Smallcaps|l}}-rhamnose
| '''Glu636'''
| Glu895
| <cite>Fujimoto2013</cite>
|-
| [[GH79]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5e9c 5e9c]
| heparanase
| ''Homo sapiens''
| heparin tetrasaccharide
| '''Glu225'''
| Glu343
| <cite>Wu2015</cite>
|-
| [[GH80]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH24''
|
|
|
|
|
|
|-
| [[GH81]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5t4g 5t4g]
| endo-β-1,3-glucanase
| ''Bacillus halodurans'' C-125
| laminarin
| '''Asp466'''
| Glu542
| <cite>Pluvinage2017</cite>
|-
| [[GH83]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1z4x 1z4x]
| hemagglutinin-neuraminidase
| Simian virus 5
| α-2,3-sialyllactose
| '''Glu247''' relay
| Tyr523
| <cite>Yuan2005</cite>
|-
| [[GH84]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2chn 2chn]
| β-''N''-acetyl-glucosaminidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| NAG-thiazoline
| '''Glu242'''
| internal
| <cite>Dennis2006</cite>
|-
| [[GH85]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w92 2w92]
| endo-β-''N''-acetyl-glucosaminidase D
| ''Streptococcus pneumoniae'' TIGR4
| NAG-thiazoline
| '''Glu337'''
| internal
| <cite>Abbott2009</cite>
|-
| [[GH86]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4aw7 4aw7]
| β-porphyranase
| ''Bacteroides plebeius''
| porphyran fragment
| '''Glu152'''
| Glu279
| <cite>Hehemann_1_2012</cite>
|-
| [[GH89]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vcb 2vcb]
| α-''N''-acetyl-glucosaminidase
| ''Clostridium perfringens''
| PUGNAc
| '''Glu483'''
| Glu601
| <cite>Ficko-Blean2008</cite>
|-
| [[GH92]]
| none
| (α/α)6 and β-sandwich
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ww1 2ww1]
| α-1,2-mannosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| thiomannobioside
| '''Glu533'''
| Asp644 Asp642
| <cite>Zhu2009</cite>
|-
| [[GH93]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3a72 3a72]
| exo-arabinanase
| ''Penicillium chrysogenum''
| arabinobiose
| '''Glu246'''
| Glu174
| <cite>Sogabe2011</cite>
|-
| [[GH94]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4zli 4zli]
| cellobionic acid phosphorylase
| ''Saccharophagus degradans''
| 3-O-β-{{Smallcaps|d}}-glucopyranosyl-α-{{Smallcaps|d}}-glucopyranuronic acid
| '''Asp472'''
| phosphate
| <cite>Nam2015</cite>
|-
| [[GH95]]
| none
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ead 2ead]
| α-1,2-{{Smallcaps|l}}-fucosidase
| ''Bifidobacterium bifidum''
| Fuc-α-1,2-Gal
| '''Glu566'''
| Asn423 Asp766
| <cite>Nagae2007</cite>
|-
| [[GH97]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining + inverting
| '''''anti'''''
| [{{PDBlink}}2zq0 2zq0]
| α-glucosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| acarbose
| '''Glu532'''
| Glu508
| <cite>Kitamura2008</cite>
|-
| [[GH98]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2wmg 2wmg]
| endo-β-1,4-galactosidase
| ''Streptococcus pneumoniae''
| A-LewisY pentasaccharide
| '''Glu158'''
| Asp251 Glu301
| <cite>Higgins2009</cite>
|-
| [[GH99]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ad4 4ad4]
| endo-α-mannosidase
| ''Bacteroides xylanisolvens''
| glucose-1,3-isofagomine and α-1,2- mannobiose
| '''Glu336'''
| debated
| <cite>Thompson2012</cite>
|-
| [[GH100]]
| none
| (α/α)6 core
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5gop 5gop]
| invertase
| ''Anabaena (Nostoc) sp.'' pcc7120
| sucrose
| '''Asp188'''
| Glu414
| <cite>Xie2016</cite>
|-
| [[GH102]]
| none
| double-ψ β-barrel
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}2pi8 2pi8]
| lytic transglycosylase A
| ''Escherichia coli''
| chitohexaose
| '''Asp308'''
| none
| <cite>van_Straaten2007</cite>
|-
| [[GH103]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1d0k 1d0k]
| lytic transglycosylase SLT35
| ''Escherichia coli''
| murodipeptides
| '''Glu162'''
| internal
| <cite>van_Asselt2000</cite>
|-
| [[GH106]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5mwk 5mwk]
| α-{{Smallcaps|l}}-rhamnosidase BT_0986
| ''Bacteroides thetaiotaomicron''
| pectin heptasaccharide
| '''Glu461'''
| Glu593 or Glu561
| <cite>Ndeh2017</cite>
|-
| [[GH107]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| ''predicted syn by clan''
| ''see at GH29''
|
|
|
|
|
|
|-
| [[GH113]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4cd8 4cd8]
| β-mannanase
| ''Alicyclobacillus acidocaldarius''
| mannobioimidazole
| '''Glu151'''
| Glu231
| <cite>Williams2014</cite>
|-
| [[GH116]]
| O
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at GH52''
|
|
|
|
|
|
|-
| [[GH117]]
| none
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}4ak7 4ak7]
| α-1,3-3,6-anhydro-{{Smallcaps|l}}-galactosidase
| ''Bacteroides plebeius''
| neoagarobiose
| '''His302'''
| Asp90
| <cite>Hehemann_2_2012</cite>
|-
| [[GH120]]
| none
| parallel β-helix and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3vsv 3vsv]
| β-xylosidase XylC
| ''Thermoanaerobacterium saccharolyticum'' JW/SL-YS485
| {{Smallcaps|d}}-xylose
| '''Glu405'''
| Asp382
| <cite>Huang2012</cite>
|-
| [[GH123]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5fr0 5fr0]
| exo-β-N-acetyl-galactosaminidase
| ''Clostridium perfringens''
| ''N''-difluoroacetyl-{{Smallcaps|d}}-galactosamine
| '''Glu345'''
| internal
| <cite>Noach2016</cite>
|-
| [[GH125]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5m7y 5m7y]
| exo-α-1,6-mannosidase
| ''Clostridium perfringens''
| 1,6-α-mannotriose
| '''Asp220'''
| Glu393
| <cite>Alonso-Gil2016</cite>
|-
| [[GH127]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3wrg 3wrg]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bifidobacterium longum''
| {{Smallcaps|l}}-arabinose
| '''Glu322'''
| Cys417
| <cite>Huang2014</cite>
|-
| [[GH128]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH1''
|
|
|
|
|
|
|-
| [[GH130]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5b0s 5b0s]
| β-1,2-mannobiose phosphorylase
| ''Listeria innocua''
| β-1,2-mannotriose
| '''Asp141''' relay
| phosphate
| <cite>Tsuda2015</cite>
|-
| [[GH134]]
| none
| β + α
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5jug 5jug]
| β-mannanase
| ''Streptomyces sp.''
| mannopentaose
| '''Glu45'''
| Asp57
| <cite>Jin2016</cite>
|-
| [[GH136]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}5gqf 5gqf]
| lacto-N-biosidase
| ''Bifidobacterium longum''
| lacto-N-biose
| '''Asp411'''
| Asp418
| <cite>Yamada2017</cite>
|-
| [[GH137]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|l}}
| unknown
| '''''anti'''''
| [{{PDBlink}}5mui 5mui]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0996
| ''Bacteroides thetaiotaomicron''
| pectin oligosaccharide
| '''Glu240'''
| Glu159
| <cite>Ndeh2017</cite>

|-
| [[GH138]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}6hzg 6hzg]
| α-1,2-{{Smallcaps|d}}-galacturonidase
| ''Bacteroides paurosaccharolyticus''
| alpha-{{Smallcaps|d}}-galactopyranuronic
| '''Glu294'''
| Glu361
| <cite>Labourel2019</cite>
|-
| [[GH146]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5opj 5opj]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0349
| ''Bacteroides thetaiotaomicron''
| {{Smallcaps|l}}-arabinose
| '''Glu320'''
| Cys416
| <cite>Luis2018</cite>
|-
| [[GH147]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH148]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH149]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH157]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH158]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH161]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH162]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}6imw 5imw]
| endo-β-1,2-glucanase
| ''Talaromyces funiculosus''
| beta-1,2-glucan
| '''Glu262''' via C3-OH of glc at subs. +2
| Asp446
| <cite>Tanaka2019</cite>
|-
| [http://www.cazy.org/GH0.html n.c.*]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2vjj 2vjj]
| endo-α-N-acetylglucosaminidase
| Bacteriophage HK620
| O18A1 O-antigen hexasaccharide
| '''Asp339'''
| Glu372
| <cite>Barbirz2008</cite>
|}
<nowiki>*</nowiki> n.c.: Found among the collection of [http://www.cazy.org/GH0.html non-classified GH sequences in the CAZy Database].

== References ==

<biblio>
# HeightmanVasella1999 Heightman TD and Vasella AT. ''Recent Insights into Inhibition, Structure, and Mechanism of Configuration-Retaining Glycosidases.'' Angew Chem Int Ed. 1999 38(6):750-770. [http://www3.interscience.wiley.com/journal/55000581/abstract Article online].
# Nerinckx2005 pmid=15642336
# Wu2012 pmid=23137336
# Perez1978 Pérez S and Marchessault RH. ''The exo-anomeric effect: experimental evidence from crystal structures.'' Carbohydr res. 1978 65:114-120. [http://dx.doi.org/10.1016/S0008-6215(00)84218-4 DOI:10.1016/S0008-6215(00)84218-4]
# Cramer1997 Cramer CJ, Truhlar DG, and French AD. ''Exo-anomeric effects on energies and geometries of different conformations of glucose and related systems in the gas phase and aqueous solution.'' Carbohydr res. 1997 298:1-14. [http://dx.doi.org/10.1016/S0008-6215(96)00297-2 DOI:10.1016/S0008-6215(96)00297-2]
# Johnson2009 pmid=19733839
# Alonso2016 pmid=26889578
# Gloster2006 pmid=17002288
# van_Bueren2009 pmid=18976664
# Hrmova2001 pmid=11709165

# Rajan2004 pmid=15341727
# Varrot2003 pmid=12595701
# Zhou1999 pmid=10508787
# Sulzenbacher1999 pmid=10200171
# Urbanikova2011 pmid=21501386
# Guerin2002 pmid=11884144
# Schubot2004 pmid=14756552
# Suzuki2009 pmid=19279191
# Wan2014 pmid=24419374
# Sandgren2004 pmid=15364577
# Uitdehaag1999 pmid=10331869
# Miyake2003 pmid=12741813
# Harris1993 pmid=8431441
# Allouch2004 pmid=15062085
# Wojtkowiak2013 pmid=23275163
# Papanikolau2001 pmid=11560481
# Prag2000 pmid=10884356
# Vocadlo2001 pmid=11518970
# Karlsen1996 pmid=15299731
# Baldwin1993 pmid=8259514
# Cartmell2008 pmid=18799462
# Fernandez-Leiro2010 pmid=20592022
# Abbott2007 pmid=17397864
# Sakurama2012 pmid=22451675
# Sim2008 pmid=18036614
# Verhaest2007 pmid=17335500
# Amaya2004 pmid=15130470
# Zhu2012 pmid=23015718
# Maksimainen2011 pmid=21130883
# Merceron2012 pmid=23012371
# Gibson2007 pmid=17455176
# Shah2008 pmid=18599462
# Czjzek2005 pmid=16212978
# Godoy2016 pmid=27685756
# Fujimoto2010 pmid=20739278
# Kitago2007 pmid=17905739
# Davies1996 pmid=15299721
# Lyu2014 pmid=24766439
# Karaveg2005 pmid=15713668
# Nerinckx2008 pmid=18619586
# Pluvinage2013 pmid=23921382

# Yuan2005 pmid=15893670
# Hoevel2003 pmid=14517232
# Espina2014 pmid=24816105
# Le_Nours2009 pmid=19089956
# Miyanaga2004 pmid=15292273
# Bianchetti2015 pmid=25752603
# Markovic-Housley2000 pmid=11080624
# Imamura2003 pmid=12618437
# Hill2013 pmid=24297913

# Maehara2014 pmid=24482228

# Miyazaki2016 pmid=27688023
# Touhara2014 pmid=24828502
# Suzuki2016 pmid=26494689
# Golan2004 pmid=14573597
# Meng2003 pmid=14517548
# Ito2011 pmid=21354427
# Hurtado-Gerrero2009 pmid=19097997
# Yaoi2007 pmid=17498741
# Thompson2015 pmid=25772148
# Barends2007 pmid=17420245
# Fujimoto2013 pmid=23486481
# Wu2015 pmid=26575439
# Pluvinage2017 pmid=28781080
# Dennis2006 pmid=16565725
# Abbott2009 pmid=19181667
# Hehemann_1_2012 pmid=23150581
# Ficko-Blean2008 pmid=18443291
# Zhu2009 pmid=20081828
# Sogabe2011 pmid=21543843
# Nam2015 pmid=26041776
# Nagae2007 pmid=17459873
# Kitamura2008 pmid=18981178
# Higgins2009 pmid=19608744
# van_Straaten2007 pmid=17502382
# van_Asselt2000 pmid=10684641
# Ndeh2017 pmid=28329766
# Labourel2019 pmid=30877196
# Luis2018 pmid=29255254
# Jin2016 Jin Y, Petricevic M, John A, Raich L, Jenkins H, Portela De Souza L, Cuskin F, Gilbert HJ, Rovira C, Goddard-Borger ED, Williams SJ, and Davies GJ. ''A β-Mannanase with a Lysozyme-like Fold and a Novel Molecular Catalytic Mechanism.'' ACS Cent Sci. 2016 Nov [http://dx.doi.org/10.1021/acscentsci.6b00232 DOI:10.1021/acscentsci.6b00232]
# Yamada2017 pmid=28392148
# Ohnuma2014 pmid=24582745
# Thompson2012 pmid=22219371
# Xie2016 pmid=27777307
# Williams2014 pmid=24339341
# Hehemann_2_2012 pmid=22393053
# Huang2012 pmid=22992047
# Noach2016 pmid=27038508
# Alonso-Gil2016 pmid=28026180
# Huang2014 Huang CH, Zhu Z, Cheng YS, Chan HC, Ko TP, Chen CC, Wang I, Ho MR, Hsu ST, Zeng YF, Huang YN, Liu JR, Guo RT. ''Structure and Catalytic Mechanism of a Glycoside Hydrolase Family-127 β-L-Arabinofuranosidase (HypBA1).'' J Bioprocess Biotech. 2014 4:171 [http://dx.doi.org/10.4172/2155-9821.1000171 DOI:10.4172/2155-9821.1000171]
# Tsuda2015 pmid=26632508
# Barbirz2008 pmid=18547389
# Tanaka2019 pmid=30926603

</biblio>

[[Category:Definitions and explanations]]

Syn/anti lateral protonation

2019-06-25T11:34:15Z

Wim Nerinckx: GH4 unusual NAD-involved beta elimination mechanism, nevertheless anti protonator

{{CuratorApproved}}
* [[Author]]: ^^^Wim Nerinckx^^^
* [[Responsible Curator]]: ^^^Spencer Williams^^^

----

== Overview ==

This page provides a table that summarizes the spatial positioning of the catalytic [[general acid]] residue in the active sites of [[glycoside hydrolase]]s, relative to the substrate. The table below updates those found in the seminal paper on this concept by Heightman and Vasella <cite>HeightmanVasella1999</cite>, and a following paper by Nerinckx ''et al.'' <cite>Nerinckx2005</cite>.

== Background ==

The ''"not from above, but from the side"'' concept of semi-lateral glycosidic oxygen [[General_acid/base|protonation]] by [[glycoside hydrolase]]s was introduced by Heightman and Vasella <cite>HeightmanVasella1999</cite>. It was originally only described for [[Anomeric centre (alpha and beta)|beta]]-equatorial [[glycoside hydrolase]]s, but appears to be equally applicable to enzymes acting on an [[Anomeric centre (alpha and beta)|alpha]]-axial glycosidic bond <cite>Nerinckx2005</cite>. When dividing [[Sub-site nomenclature|subsite -1]] into half-spaces by a plane defined by the glycosidic oxygen and C1' and H1' of the –1 glycoside, many ligand-complexed structures reveal that the [[General_acid/base|proton donor]] is positioned either in the ''syn'' half-space (near the ring-oxygen of the –1 glycoside), or in the ''anti'' half-space (on the opposite side of the ring-oxygen). Members of the same GH [[Families|family]] appear to share a common ''syn'' or ''anti'' [[General_acid/base|protonator]] arrangement and further, this specificity appears to be preserved within [[Clans|Clans]] of [[Families|families]]. This page's compilation of [[Sub-site nomenclature|subsite -1]] occupied complexes shows that about 70% of all GH [[Families|families]] are ''anti'' [[General_acid/base|protonators]].

Closer inspection of crystal structures of [[Sub-site nomenclature|–1/+1 subsite]]-spanning substrates, or substrate-analogue ligands, in complex with enzymes reveals a further intriguing corollary <cite>Nerinckx2005 Wu2012</cite>. In substrate-bound complexes with ''anti'' [[General_acid/base|protonating]] GH enzymes, the scissile [[Anomeric centre (alpha and beta)|anomeric bond]] (often studied using the thio-analogue) shows a dihedral angle φ (O5'-C1'-[O,S]x-Cx) that is in the lowest-energy synclinal (gauche) conformation. The rationale for this is that a minus synclinal dihedral angle φ for an equatorial glycosidic bond, or plus synclinal for an axial glycosidic bond <cite>Perez1978</cite>, allows for hyperconjugative overlap of the C1'-O5' antibonding orbital with an antiperiplanar-oriented lone pair orbital lobe of the glycosidic oxygen, thereby creating partial double bond character and stabilization of the glycosidic bond by 4–5 kcal/mol; this ground-state stabilizing phenomenon is known as the ‘exo-anomeric effect’ <cite>Cramer1997 Johnson2009 Alonso2016</cite>. ''Anti'' [[General_acid/base|protonation]] occurs on the glycosidic oxygen’s antiperiplanar lone pair, thereby removing the stabilizing exo-anomeric effect. This suggests that ''anti'' [[General_acid/base|protonation]] is an enzymic approach for lowering the activation barrier leading to the [[Transition state|transition state]] (Figure 1 centre).

''Syn'' [[General_acid/base|protonating]] [[glycoside hydrolase]]s apparently make use of a different approach <cite>Nerinckx2005 Wu2012</cite>. In many [[Sub-site nomenclature|–1/+1 subsite]]-spanning ligand complexes, the dihedral angle φ of the scissile anomeric bond has been rotated away from its lowest-energy synclinal position: clockwise to minus-anticlinal or antiperiplanar for beta-equatorial; counterclockwise to plus-anticlinal or antiperiplanar for alpha-axial [[Anomeric centre (alpha and beta)|anomeric bonds]]. This removes the hyperconjugative overlap and thus also the stabilizing exo-anomeric effect. And because of this rotation, a lone pair of the glycosidic oxygen is directed into the ''syn'' half-space, allowing it to be protonated by the ''syn''-positioned [[General_acid/base|proton donor]] (Figure 1 right).

[[File:Syn_anti.jpg|800px|thumb|center|Figure 1. Newman projections, with the glycosidic oxygen as proximal atom and the anomeric carbon as distal atom, showing ''anti'' (centre) versus ''syn'' (right) semi-lateral [[General_acid/base|protonation]] in beta-equatorial (top) and alpha-axial (bottom) [[glycoside hydrolase]]s. The indicated φ is the dihedral angle for O5'-C1'-O4-C4.]]

== Table of ''syn/anti'' protonation examples ==

This table contains only one example per GH [[Families|family]] of a ligand-complexed protein structure where the ''syn'' or ''anti'' positioning of the [[General_acid/base|proton donor]] can be clearly observed; other examples may be available on a [[Families|family-by-family]] basis. The reader is thus advised to consult the [http://www.cazy.org/fam/acc_GH.html#table CAZy database] for a current, comprehensive list of CAZyme structures. Where available, the selected examples are Michaelis-type complexes with the ligand spanning the [[Sub-site nomenclature|-1/+1 subsites]], since these have an intact glycosidic or thioglycosidic bond, or are ''N''-analogs of the substrate (''e.g.'' acarbose). In some examples, the [[General_acid/base|proton donor]] has been mutated (''e.g.'', to the corresponding amide or to an alanine), and in those cases one may wish to look at a superposition of the given PDB example with the structure of the native enzyme. If a Michaelis-type complex is not yet available, the second and third example choices, respectively, are trapped glycosyl-enzyme [[intermediate]]s and product complexes where [[Sub-site nomenclature|subsite -1]] is occupied.

''Please also be aware that this is a large table with many data. Please contact the page Author or Responsible Curator with corrections.''

=== Table ===
This table can be re-sorted by clicking on the icons in the header (''javascript must be turned on in your browser''). To reset the page to be sorted by GH family, click the ''View'' tab at the very top of the page.

{| {{Prettytable}} class="sortable"
|- valign="top"
! '''Family'''
! '''Clan'''
! '''Structure fold '''
! '''Anomeric specificity'''
! '''Mechanism'''
! '''''Syn/anti'' protonator'''
! '''Example PDB ID'''
! '''Enzyme'''
! '''Organism'''
! '''Ligand'''
! '''General acid'''
! '''Nucleophile or General base'''
! '''Reference'''
|-
| [[GH1]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2cer 2cer]
| β-glycosidase S
| ''Sulfolobus solfataricus'' P2
| phenethyl glucoimidazole
| '''Glu206'''
| Glu387
| <cite>Gloster2006</cite>
|-
| [[GH2]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vzu 2vzu]
| exo-β-glucosaminidase
| ''Amicolatopsis orientalis''
| PNP-β-{{Smallcaps|d}}-glucosamine
| '''Glu469'''
| Glu541
| <cite>van_Bueren2009</cite>
|-
| [[GH3]]
| none
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1iex 1iex]
| exo-1,3-1,4-glucanase
| ''Hordeum vulgare''
| thiocellobiose
| '''Glu491'''
| Asp285
| <cite>Hrmova2001</cite>
|-
| [[GH4]]
| none
| Rossmann + α6/β3 + β3/α4
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1u8x 1u8x]
| 6-P-α-glucosidase
| ''Bacillus subtilis''
| alpha-{{Smallcaps|d}}-glucose-6-phosphate
| '''Asp172'''
| Not applicable
| <cite>Rajan2004</cite>
|-

| [[GH5]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1h2j 1h2j]
| endo-β-1,4-glucanase
| ''Bacillus agaradhaerens''
| 2',4'-DNP-2-F-cellobioside
| '''Glu129'''
| Glu228
| <cite>Varrot2003</cite>
|-
| [[GH6]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1qjw 1qjw]
| cellobiohydrolase 2
| ''Hypocrea jecorina''
| (Glc)2-S-(Glc)2
| '''Asp221'''
| debated
| <cite>Zhou1999</cite>
|-
| [[GH7]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1ovw 1ovw]
| endo-1,4-glucanase
| ''Fusarium oxysporum''
| thio-(Glc)5
| '''Glu202'''
| Glu197
| <cite>Sulzenbacher1999</cite>
|-
| [[GH8]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1kwf 1kwf]
| endo-1,4-glucanase
| ''Clostridium thermocellum''
| cellopentaose
| '''Glu95'''
| Asp278
| <cite>Guerin2002</cite>
|-
| [[GH9]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1rq5 1rq5]
| cellobiohydrolase
| ''Clostridium thermocellum''
| cellotetraose
| '''Glu795'''
| Asp383
| <cite>Schubot2004</cite>
|-
| [[GH10]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2d24 2d24]
| β-1,4-xylanase
| ''Streptomyces olivaceoviridis'' E-86
| xylopentaose
| '''Glu128'''
| Glu236
| <cite>Suzuki2009</cite>
|-
| [[GH11]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}4hk8 4hk8]
| endo-β-1,4-xylanase
| ''Hypocrea jecorina''
| xylohexaose
| '''Glu177'''
| Glu86
| <cite>Wan2014</cite>
|-
| [[GH12]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1w2u 1w2u]
| endoglucanase
| ''Humicola grisea''
| thiocellotetraose
| '''Glu205'''
| Glu120
| <cite>Sandgren2004</cite>
|-
| [[GH13]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1cxk 1cxk]
| β-cyclodextrin glucanotransferase
| ''Bacillus circulans''
| maltononaose
| '''Glu257'''
| Asp229
| <cite>Uitdehaag1999</cite>
|-
| [[GH14]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1itc 1itc]
| β-amylase
| ''Bacillus cereus''
| maltopentaose
| '''Glu172'''
| Glu367
| <cite>Miyake2003</cite>
|-
| [[GH15]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1dog 1dog]
| glucoamylase
| ''Aspergillus awamori''
| 1-deoxynojirimycin
| '''Glu179'''
| Glu400
| <cite>Harris1993</cite>
|-
| [[GH16]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1urx 1urx]
| β-agarase A
| ''Zobellia galactanivorans''
| oligoagarose
| '''Glu152'''
| Glu147
| <cite>Allouch2004</cite>
|-
| [[GH17]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzj 4gzj]
| endo-β-1,3-glucanase
| ''Solanum tuberosum''
| laminaratriose + laminarabiose
| '''Glu118'''
| Glu259
| <cite>Wojtkowiak2013</cite>
|-
| [[GH18]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1ffr 1ffr]
| chitinase A
| ''Serratia marcescens''
| (NAG)6
| '''Glu315'''
| internal
| <cite>Papanikolau2001</cite>
|-
| [[GH19]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}3wh1 3wh1]
| chitinase
| ''Bryum coronatum''
| (GlcNAc)4
| '''Glu61'''
| Glu70
| <cite>Ohnuma2014</cite>
|-
| [[GH20]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1c7s 1c7s]
| chitobiase
| ''Serratia marcescens''
| chitobiose
| '''Glu540'''
| internal
| <cite>Prag2000</cite>
|-
| [[GH22]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1h6m 1h6m]
| lysozyme C
| ''Gallus gallus''
| Chit-2-F-chitosyl
| '''Glu35'''
| Asp52
| <cite>Vocadlo2001</cite>
|-
| [[GH23]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1lsp 1lsp]
| lysozyme G
| ''Cygnus atratus''
| Bulgecin A
| '''Glu73'''
| internal
| <cite>Karlsen1996</cite>
|-
| [[GH24]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}148l 148l]
| lysozyme E
| Bacteriophage T4
| chitobiosyl
| '''Glu11'''
| Glu26
| <cite>Baldwin1993</cite>
|-
| [[GH26]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vx6 2vx6]
| exo-β-mannanase
| ''Cellvibrio japonicus'' Ueda107
| Gal1Man4
| '''Glu221'''
| Glu338
| <cite>Cartmell2008</cite>
|-
| [[GH27]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}} / beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3lrm 3lrm]
| α-galactosidase
| ''Saccharomyces cerevisiae''
| raffinose
| '''Asp209'''
| Asp141
| <cite>Fernandez-Leiro2010</cite>
|-
| [[GH28]]
| N
| β-helix
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}2uvf 2uvf]
| exo-polygalacturonosidase
| ''Yersinia enterocolitica'' ATCC9610D
| digalacturonic acid
| '''Asp402'''
| Asp381 Asp403
| <cite>Abbott2007</cite>
|-
| [[GH29]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| '''''syn'''''
| [{{PDBlink}}3uet 3uet]
| α-1,3/4-fucosidase
| ''Bifidobacterium longum'' subsp. infantis
| lacto-''N''-fucopentaose II
| '''Glu217'''
| Asp172
| <cite>Sakurama2012</cite>
|-
| [[GH30]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2y24 2y24]
| glucurono-xylanase
| ''Dickea chrysanthemi'' D1
| glucuronoxylan tetrasaccharide
| '''Glu163'''
| Glu253
| <cite>Urbanikova2011</cite>
|-
| [[GH31]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2qmj 2qmj]
| maltase-glucoamylase
| ''Homo sapiens''
| acarbose
| '''Asp542'''
| Asp443
| <cite>Sim2008</cite>
|-
| [[GH32]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2add 2add]
| fructan β-(2,1)-fructosidase
| ''Cichorium intybus''
| sucrose
| '''Glu201'''
| Asp22
| <cite>Verhaest2007</cite>
|-
| [[GH33]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1s0i 1s0i]
| transsialidase
| ''Trypanosoma cruzi''
| sialyllactose
| '''Asp59'''
| Tyr342
| <cite>Amaya2004</cite>
|-
| [[GH34]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzw 4gzw]
| N2 neuraminidase
| ''Influenza'' A Tanzania/205/2010 H3N2
| α-{{Smallcaps|d}}-Neup5Ac-(2,3)-β-{{Smallcaps|d}}-Galp-(1,4)-β-{{Smallcaps|d}}-GlcpNAc
| '''Asp151'''
| Tyr406
| <cite>Zhu2012</cite>
|-
| [[GH35]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3ogv 3ogv]
| β-galactosidase
| ''Hypocrea jecorina''
| 2-phenylethyl 1-thio-β-{{Smallcaps|d}}-galactopyranoside
| '''Glu200'''
| Glu298
| <cite>Maksimainen2011</cite>
|-
| [[GH36]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4fns 4fns]
| β-galactosidase
| ''Geobacillus stearothermophilus''
| 1-deoxy galactonojirimycin
| '''Asp584'''
| Asp478
| <cite>Merceron2012</cite>
|-
| [[GH37]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2jf4 2jf4]
| trehalase
| ''Escherichia coli''
| validoxylamine
| '''Asp312'''
| Glu496
| <cite>Gibson2007</cite>
|-
| [[GH38]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3czn 3czn]
| Golgi α-mannosidase II
| ''Drosophila melanogaster''
| GlcNAcMan(5)GlcNAc(2)
| '''Asp341'''
| Asp204
| <cite>Shah2008</cite>
|-
| [[GH39]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2bfg 2bfg]
| β-xylosidase
| ''Geobacillus stearothermophilus''
| 2,5-dinitrophenyl-β-{{Smallcaps|d}}-xyloside
| '''Glu160'''
| Glu278
| <cite>Czjzek2005</cite>
|-
| [[GH42]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ucf 4ucf]
| β-galactosidase
| ''Bifidobacterium bifidum''
| {{Smallcaps|d}}-galactose
| '''Glu161'''
| Glu320
| <cite>Godoy2016</cite>
|-
| [[GH43]]
| F
| 5-fold β-propeller
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3akh 3akh]
| exo-1,5-α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces avermitilis''
| α-1,5-arabinofuranotriose
| '''Glu196'''
| Asp220
| <cite>Fujimoto2010</cite>
|-
| [[GH44]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2eqd 2eqd]
| endoglucanase
| ''Clostridium thermocellum''
| cellooctaose
| '''Glu186'''
| Glu359
| <cite>Kitago2007</cite>
|-
| [[GH45]]
| none
| 6-stranded β-barrel
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4eng 4eng]
| endo-1,4-glucanase
| ''Humicola insolens''
| cellohexaose
| '''Asp121'''
| Asp10
| <cite>Davies1996</cite>
|-
| [[GH46]]
| I
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4olt 4olt]
| chitosanase
| ''Microbacterium sp.'' OU01
| hexa-glucosamine
| '''Glu25'''
| Asp43
| <cite>Lyu2014</cite>
|-
| [[GH47]]
| none
| (α/α)7
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1x9d 1x9d]
| α-mannosidase I
| ''Homo sapiens''
| Me-2-S-(α-Man)-2-thio-α-Man
| '''Asp463'''
| Glu599
| <cite>Karaveg2005</cite>, <cite>Nerinckx2008</cite>
|-
| [[GH48]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH8''
|
|
|
|
|
|
|-
| [[GH49]]
| N
| β-helix
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH28''
|
|
|
|
|
|
|-
| [[GH50]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4bq5 4bq5]
| exo-β-agarase
| ''Saccharophagus degradans''
| neoagarotetraose
| '''Glu535'''
| Glu695
| <cite>Pluvinage2013</cite>
|-
| [[GH51]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1qw9 1qw9]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Geobacillus stearothermophilus''
| PNP-{{Smallcaps|l}}-arabinofuranoside
| '''Glu175'''
| Glu294
| <cite>Hoevel2003</cite>
|-
| [[GH52]]
| O
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4c1p 4c1p]
| β-xylosidase
| ''Geobacillus thermoglucosidasius''
| xylobiose
| '''Asp517'''
| Glu537
| <cite>Espina2014</cite>
|-
| [[GH53]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2ccr 2ccr]
| β-1,4-galactanase
| ''Bacillus licheniformis''
| galactotriose
| '''Glu165'''
| Glu263
| <cite>Le_Nours2009</cite>
|-
| [[GH54]]
| none
| β-sandwich
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1wd4 1wd4]
| α-{{Smallcaps|l}}-arabinofuranosidase B
| ''Aspergillus kawachii''
| {{Smallcaps|l}}-arabinofuranose
| '''Asp297'''
| Glu221
| <cite>Miyanaga2004</cite>
|-
| [[GH55]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4tz5 4tz5]
| exo-β-1,3-glucanase
| ''Streptomyces sp.'' SirexAA-E
| laminarihexaose
| '''Glu502'''
| unknown
| <cite>Bianchetti2015</cite>
|-
| [[GH56]]
| none
| (β/α)7
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1fcv 1fcv]
| hyaluronidase
| ''Apis mellifera''
| (hyaluron.)4
| '''Glu113'''
| internal
| <cite>Markovic-Housley2000</cite>
|-
| [[GH57]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1k1y 1k1y]
| glucanotransferase
| ''Thermococcus litoralis''
| acarbose
| '''Asp214'''
| Glu123
| <cite>Imamura2003</cite>
|-
| [[GH59]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ccc 4ccc]
| β-galactocerebrosidase
| ''Mus musculus''
| PNP-β-{{Smallcaps|d}}-galactoside
| '''Glu182'''
| Glu258
| <cite>Hill2013</cite>
|-
| [[GH62]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3wn0 3wn0]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces coelicolor''
| β-{{Smallcaps|l}}-Arabinofuranose
| '''Glu361'''
| Asp202
| <cite>Maehara2014</cite>
|-
| [[GH63]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5ca3 5ca3]
| α-glucosidase
| ''Escherichia coli''
| glucose and lactose
| '''Asp501'''
| Glu727
| <cite>Miyazaki2016</cite>
|-
| [[GH65]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}4ktr 4ktr]
| 2-O-α-glucosylglycerol phosphorylase
| ''Bacillus selenitireducens''
| isofagomine
| '''Glu475'''
| phosphate
| <cite>Touhara2014</cite>
|-
| [[GH66]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5axh 5axh]
| dextranase
| ''Thermoanaerobacter pseudethanolicus''
| isomaltohexaose
| '''Glu374'''
| Asp312
| <cite>Suzuki2016</cite>
|-
| [[GH67]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1l8n 1l8n]
| α-glucuronidase
| ''Geobacillus stearothermophilus''
| 4-O-methyl-{{Smallcaps|d}}-glucuronic acid and xylotriose
| '''Glu286'''
| Asp364 Glu392
| <cite>Golan2004</cite>
|-
| [[GH68]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1pt2 1pt2]
| levansucrase
| ''Bacillus subtilis''
| sucrose
| '''Glu342'''
| Asp86
| <cite>Meng2003</cite>
|-
| [[GH70]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3aic 3aic]
| glucansucrase
| ''Streptococcus mutans''
| α-acarbose
| '''Glu515'''
| Asp477
| <cite>Ito2011</cite>
|-
| [[GH72]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w62 2w62]
| β-1,3-glucanotransferase
| ''Saccharomyces cerevisiae'' S288C
| laminaripentaose
| '''Glu176'''
| Glu275
| <cite>Hurtado-Gerrero2009</cite>
|-
| [[GH74]]
| none
| 7-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}2ebs 2ebs]
| cellobiohydrolase (OXG-RCBH)
| ''Geotrichum sp.'' m128
| xyloglucan heptasaccharide
| '''Asp465'''
| Asp35
| <cite>Yaoi2007</cite>
|-
| [[GH76]]
| none
| (α/α)6
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5agd 5agd]
| endo-α-1,6-mannanase
| ''Bacillus circulans''
| α-1,6-mannopentaose
| '''Asp125'''
| Asp124
| <cite>Thompson2015</cite>
|-
| [[GH77]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2oww 2oww]
| 4-α-glucanotransferase
| ''Thermus thermofilus''
| acarbose + 4-deoxy-α-{{Smallcaps|d}}-glucose
| '''Glu340'''
| Asp293
| <cite>Barends2007</cite>
|-
| [[GH78]]
| H
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3w5n 3w5n]
| α-{{Smallcaps|l}}-rhamnosidase
| ''Streptomyces avermitilis''
| {{Smallcaps|l}}-rhamnose
| '''Glu636'''
| Glu895
| <cite>Fujimoto2013</cite>
|-
| [[GH79]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5e9c 5e9c]
| heparanase
| ''Homo sapiens''
| heparin tetrasaccharide
| '''Glu225'''
| Glu343
| <cite>Wu2015</cite>
|-
| [[GH80]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH24''
|
|
|
|
|
|
|-
| [[GH81]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5t4g 5t4g]
| endo-β-1,3-glucanase
| ''Bacillus halodurans'' C-125
| laminarin
| '''Asp466'''
| Glu542
| <cite>Pluvinage2017</cite>
|-
| [[GH83]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1z4x 1z4x]
| hemagglutinin-neuraminidase
| Simian virus 5
| α-2,3-sialyllactose
| '''Glu247''' relay
| Tyr523
| <cite>Yuan2005</cite>
|-
| [[GH84]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2chn 2chn]
| β-''N''-acetyl-glucosaminidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| NAG-thiazoline
| '''Glu242'''
| internal
| <cite>Dennis2006</cite>
|-
| [[GH85]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w92 2w92]
| endo-β-''N''-acetyl-glucosaminidase D
| ''Streptococcus pneumoniae'' TIGR4
| NAG-thiazoline
| '''Glu337'''
| internal
| <cite>Abbott2009</cite>
|-
| [[GH86]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4aw7 4aw7]
| β-porphyranase
| ''Bacteroides plebeius''
| porphyran fragment
| '''Glu152'''
| Glu279
| <cite>Hehemann_1_2012</cite>
|-
| [[GH89]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vcb 2vcb]
| α-''N''-acetyl-glucosaminidase
| ''Clostridium perfringens''
| PUGNAc
| '''Glu483'''
| Glu601
| <cite>Ficko-Blean2008</cite>
|-
| [[GH92]]
| none
| (α/α)6 and β-sandwich
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ww1 2ww1]
| α-1,2-mannosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| thiomannobioside
| '''Glu533'''
| Asp644 Asp642
| <cite>Zhu2009</cite>
|-
| [[GH93]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3a72 3a72]
| exo-arabinanase
| ''Penicillium chrysogenum''
| arabinobiose
| '''Glu246'''
| Glu174
| <cite>Sogabe2011</cite>
|-
| [[GH94]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4zli 4zli]
| cellobionic acid phosphorylase
| ''Saccharophagus degradans''
| 3-O-β-{{Smallcaps|d}}-glucopyranosyl-α-{{Smallcaps|d}}-glucopyranuronic acid
| '''Asp472'''
| phosphate
| <cite>Nam2015</cite>
|-
| [[GH95]]
| none
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ead 2ead]
| α-1,2-{{Smallcaps|l}}-fucosidase
| ''Bifidobacterium bifidum''
| Fuc-α-1,2-Gal
| '''Glu566'''
| Asn423 Asp766
| <cite>Nagae2007</cite>
|-
| [[GH97]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining + inverting
| '''''anti'''''
| [{{PDBlink}}2zq0 2zq0]
| α-glucosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| acarbose
| '''Glu532'''
| Glu508
| <cite>Kitamura2008</cite>
|-
| [[GH98]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2wmg 2wmg]
| endo-β-1,4-galactosidase
| ''Streptococcus pneumoniae''
| A-LewisY pentasaccharide
| '''Glu158'''
| Asp251 Glu301
| <cite>Higgins2009</cite>
|-
| [[GH99]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ad4 4ad4]
| endo-α-mannosidase
| ''Bacteroides xylanisolvens''
| glucose-1,3-isofagomine and α-1,2- mannobiose
| '''Glu336'''
| debated
| <cite>Thompson2012</cite>
|-
| [[GH100]]
| none
| (α/α)6 core
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5gop 5gop]
| invertase
| ''Anabaena (Nostoc) sp.'' pcc7120
| sucrose
| '''Asp188'''
| Glu414
| <cite>Xie2016</cite>
|-
| [[GH102]]
| none
| double-ψ β-barrel
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}2pi8 2pi8]
| lytic transglycosylase A
| ''Escherichia coli''
| chitohexaose
| '''Asp308'''
| none
| <cite>van_Straaten2007</cite>
|-
| [[GH103]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1d0k 1d0k]
| lytic transglycosylase SLT35
| ''Escherichia coli''
| murodipeptides
| '''Glu162'''
| internal
| <cite>van_Asselt2000</cite>
|-
| [[GH106]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5mwk 5mwk]
| α-{{Smallcaps|l}}-rhamnosidase BT_0986
| ''Bacteroides thetaiotaomicron''
| pectin heptasaccharide
| '''Glu461'''
| Glu593 or Glu561
| <cite>Ndeh2017</cite>
|-
| [[GH107]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| ''predicted syn by clan''
| ''see at GH29''
|
|
|
|
|
|
|-
| [[GH113]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4cd8 4cd8]
| β-mannanase
| ''Alicyclobacillus acidocaldarius''
| mannobioimidazole
| '''Glu151'''
| Glu231
| <cite>Williams2014</cite>
|-
| [[GH116]]
| O
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at GH52''
|
|
|
|
|
|
|-
| [[GH117]]
| none
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}4ak7 4ak7]
| α-1,3-3,6-anhydro-{{Smallcaps|l}}-galactosidase
| ''Bacteroides plebeius''
| neoagarobiose
| '''His302'''
| Asp90
| <cite>Hehemann_2_2012</cite>
|-
| [[GH120]]
| none
| parallel β-helix and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3vsv 3vsv]
| β-xylosidase XylC
| ''Thermoanaerobacterium saccharolyticum'' JW/SL-YS485
| {{Smallcaps|d}}-xylose
| '''Glu405'''
| Asp382
| <cite>Huang2012</cite>
|-
| [[GH123]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5fr0 5fr0]
| exo-β-N-acetyl-galactosaminidase
| ''Clostridium perfringens''
| ''N''-difluoroacetyl-{{Smallcaps|d}}-galactosamine
| '''Glu345'''
| internal
| <cite>Noach2016</cite>
|-
| [[GH125]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5m7y 5m7y]
| exo-α-1,6-mannosidase
| ''Clostridium perfringens''
| 1,6-α-mannotriose
| '''Asp220'''
| Glu393
| <cite>Alonso-Gil2016</cite>
|-
| [[GH127]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3wrg 3wrg]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bifidobacterium longum''
| {{Smallcaps|l}}-arabinose
| '''Glu322'''
| Cys417
| <cite>Huang2014</cite>
|-
| [[GH128]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH1''
|
|
|
|
|
|
|-
| [[GH130]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5b0s 5b0s]
| β-1,2-mannobiose phosphorylase
| ''Listeria innocua''
| β-1,2-mannotriose
| '''Asp141''' relay
| phosphate
| <cite>Tsuda2015</cite>
|-
| [[GH134]]
| none
| β + α
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5jug 5jug]
| β-mannanase
| ''Streptomyces sp.''
| mannopentaose
| '''Glu45'''
| Asp57
| <cite>Jin2016</cite>
|-
| [[GH136]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}5gqf 5gqf]
| lacto-N-biosidase
| ''Bifidobacterium longum''
| lacto-N-biose
| '''Asp411'''
| Asp418
| <cite>Yamada2017</cite>
|-
| [[GH137]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|l}}
| unknown
| '''''anti'''''
| [{{PDBlink}}5mui 5mui]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0996
| ''Bacteroides thetaiotaomicron''
| pectin oligosaccharide
| '''Glu240'''
| Glu159
| <cite>Ndeh2017</cite>

|-
| [[GH138]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}6hzg 6hzg]
| α-1,2-{{Smallcaps|d}}-galacturonidase
| ''Bacteroides paurosaccharolyticus''
| alpha-{{Smallcaps|d}}-galactopyranuronic
| '''Glu294'''
| Glu361
| <cite>Labourel2019</cite>
|-
| [[GH146]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5opj 5opj]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0349
| ''Bacteroides thetaiotaomicron''
| {{Smallcaps|l}}-arabinose
| '''Glu320'''
| Cys416
| <cite>Luis2018</cite>
|-
| [[GH147]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH148]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH149]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH157]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH158]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH161]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH162]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}6imw 5imw]
| endo-β-1,2-glucanase
| ''Talaromyces funiculosus''
| beta-1,2-glucan
| '''Glu262'''
| Asp446
| <cite>Tanaka2019</cite>
|-
| [http://www.cazy.org/GH0.html n.c.*]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2vjj 2vjj]
| endo-α-N-acetylglucosaminidase
| Bacteriophage HK620
| O18A1 O-antigen hexasaccharide
| '''Asp339'''
| Glu372
| <cite>Barbirz2008</cite>
|}
<nowiki>*</nowiki> n.c.: Found among the collection of [http://www.cazy.org/GH0.html non-classified GH sequences in the CAZy Database].

== References ==

<biblio>
# HeightmanVasella1999 Heightman TD and Vasella AT. ''Recent Insights into Inhibition, Structure, and Mechanism of Configuration-Retaining Glycosidases.'' Angew Chem Int Ed. 1999 38(6):750-770. [http://www3.interscience.wiley.com/journal/55000581/abstract Article online].
# Nerinckx2005 pmid=15642336
# Wu2012 pmid=23137336
# Perez1978 Pérez S and Marchessault RH. ''The exo-anomeric effect: experimental evidence from crystal structures.'' Carbohydr res. 1978 65:114-120. [http://dx.doi.org/10.1016/S0008-6215(00)84218-4 DOI:10.1016/S0008-6215(00)84218-4]
# Cramer1997 Cramer CJ, Truhlar DG, and French AD. ''Exo-anomeric effects on energies and geometries of different conformations of glucose and related systems in the gas phase and aqueous solution.'' Carbohydr res. 1997 298:1-14. [http://dx.doi.org/10.1016/S0008-6215(96)00297-2 DOI:10.1016/S0008-6215(96)00297-2]
# Johnson2009 pmid=19733839
# Alonso2016 pmid=26889578
# Gloster2006 pmid=17002288
# van_Bueren2009 pmid=18976664
# Hrmova2001 pmid=11709165

# Rajan2004 pmid=15341727
# Varrot2003 pmid=12595701
# Zhou1999 pmid=10508787
# Sulzenbacher1999 pmid=10200171
# Urbanikova2011 pmid=21501386
# Guerin2002 pmid=11884144
# Schubot2004 pmid=14756552
# Suzuki2009 pmid=19279191
# Wan2014 pmid=24419374
# Sandgren2004 pmid=15364577
# Uitdehaag1999 pmid=10331869
# Miyake2003 pmid=12741813
# Harris1993 pmid=8431441
# Allouch2004 pmid=15062085
# Wojtkowiak2013 pmid=23275163
# Papanikolau2001 pmid=11560481
# Prag2000 pmid=10884356
# Vocadlo2001 pmid=11518970
# Karlsen1996 pmid=15299731
# Baldwin1993 pmid=8259514
# Cartmell2008 pmid=18799462
# Fernandez-Leiro2010 pmid=20592022
# Abbott2007 pmid=17397864
# Sakurama2012 pmid=22451675
# Sim2008 pmid=18036614
# Verhaest2007 pmid=17335500
# Amaya2004 pmid=15130470
# Zhu2012 pmid=23015718
# Maksimainen2011 pmid=21130883
# Merceron2012 pmid=23012371
# Gibson2007 pmid=17455176
# Shah2008 pmid=18599462
# Czjzek2005 pmid=16212978
# Godoy2016 pmid=27685756
# Fujimoto2010 pmid=20739278
# Kitago2007 pmid=17905739
# Davies1996 pmid=15299721
# Lyu2014 pmid=24766439
# Karaveg2005 pmid=15713668
# Nerinckx2008 pmid=18619586
# Pluvinage2013 pmid=23921382

# Yuan2005 pmid=15893670
# Hoevel2003 pmid=14517232
# Espina2014 pmid=24816105
# Le_Nours2009 pmid=19089956
# Miyanaga2004 pmid=15292273
# Bianchetti2015 pmid=25752603
# Markovic-Housley2000 pmid=11080624
# Imamura2003 pmid=12618437
# Hill2013 pmid=24297913

# Maehara2014 pmid=24482228

# Miyazaki2016 pmid=27688023
# Touhara2014 pmid=24828502
# Suzuki2016 pmid=26494689
# Golan2004 pmid=14573597
# Meng2003 pmid=14517548
# Ito2011 pmid=21354427
# Hurtado-Gerrero2009 pmid=19097997
# Yaoi2007 pmid=17498741
# Thompson2015 pmid=25772148
# Barends2007 pmid=17420245
# Fujimoto2013 pmid=23486481
# Wu2015 pmid=26575439
# Pluvinage2017 pmid=28781080
# Dennis2006 pmid=16565725
# Abbott2009 pmid=19181667
# Hehemann_1_2012 pmid=23150581
# Ficko-Blean2008 pmid=18443291
# Zhu2009 pmid=20081828
# Sogabe2011 pmid=21543843
# Nam2015 pmid=26041776
# Nagae2007 pmid=17459873
# Kitamura2008 pmid=18981178
# Higgins2009 pmid=19608744
# van_Straaten2007 pmid=17502382
# van_Asselt2000 pmid=10684641
# Ndeh2017 pmid=28329766
# Labourel2019 pmid=30877196
# Luis2018 pmid=29255254
# Jin2016 Jin Y, Petricevic M, John A, Raich L, Jenkins H, Portela De Souza L, Cuskin F, Gilbert HJ, Rovira C, Goddard-Borger ED, Williams SJ, and Davies GJ. ''A β-Mannanase with a Lysozyme-like Fold and a Novel Molecular Catalytic Mechanism.'' ACS Cent Sci. 2016 Nov [http://dx.doi.org/10.1021/acscentsci.6b00232 DOI:10.1021/acscentsci.6b00232]
# Yamada2017 pmid=28392148
# Ohnuma2014 pmid=24582745
# Thompson2012 pmid=22219371
# Xie2016 pmid=27777307
# Williams2014 pmid=24339341
# Hehemann_2_2012 pmid=22393053
# Huang2012 pmid=22992047
# Noach2016 pmid=27038508
# Alonso-Gil2016 pmid=28026180
# Huang2014 Huang CH, Zhu Z, Cheng YS, Chan HC, Ko TP, Chen CC, Wang I, Ho MR, Hsu ST, Zeng YF, Huang YN, Liu JR, Guo RT. ''Structure and Catalytic Mechanism of a Glycoside Hydrolase Family-127 β-L-Arabinofuranosidase (HypBA1).'' J Bioprocess Biotech. 2014 4:171 [http://dx.doi.org/10.4172/2155-9821.1000171 DOI:10.4172/2155-9821.1000171]
# Tsuda2015 pmid=26632508
# Barbirz2008 pmid=18547389
# Tanaka2019 pmid=30926603

</biblio>

[[Category:Definitions and explanations]]

Syn/anti lateral protonation

2019-05-29T21:16:16Z

Wim Nerinckx:

{{CuratorApproved}}
* [[Author]]: ^^^Wim Nerinckx^^^
* [[Responsible Curator]]: ^^^Spencer Williams^^^

----

== Overview ==

This page provides a table that summarizes the spatial positioning of the catalytic [[general acid]] residue in the active sites of [[glycoside hydrolase]]s, relative to the substrate. The table below updates those found in the seminal paper on this concept by Heightman and Vasella <cite>HeightmanVasella1999</cite>, and a following paper by Nerinckx ''et al.'' <cite>Nerinckx2005</cite>.

== Background ==

The ''"not from above, but from the side"'' concept of semi-lateral glycosidic oxygen [[General_acid/base|protonation]] by [[glycoside hydrolase]]s was introduced by Heightman and Vasella <cite>HeightmanVasella1999</cite>. It was originally only described for [[Anomeric centre (alpha and beta)|beta]]-equatorial [[glycoside hydrolase]]s, but appears to be equally applicable to enzymes acting on an [[Anomeric centre (alpha and beta)|alpha]]-axial glycosidic bond <cite>Nerinckx2005</cite>. When dividing [[Sub-site nomenclature|subsite -1]] into half-spaces by a plane defined by the glycosidic oxygen and C1' and H1' of the –1 glycoside, many ligand-complexed structures reveal that the [[General_acid/base|proton donor]] is positioned either in the ''syn'' half-space (near the ring-oxygen of the –1 glycoside), or in the ''anti'' half-space (on the opposite side of the ring-oxygen). Members of the same GH [[Families|family]] appear to share a common ''syn'' or ''anti'' [[General_acid/base|protonator]] arrangement and further, this specificity appears to be preserved within [[Clans|Clans]] of [[Families|families]]. This page's compilation of [[Sub-site nomenclature|subsite -1]] occupied complexes shows that about 70% of all GH [[Families|families]] are ''anti'' [[General_acid/base|protonators]].

Closer inspection of crystal structures of [[Sub-site nomenclature|–1/+1 subsite]]-spanning substrates, or substrate-analogue ligands, in complex with enzymes reveals a further intriguing corollary <cite>Nerinckx2005 Wu2012</cite>. In substrate-bound complexes with ''anti'' [[General_acid/base|protonating]] GH enzymes, the scissile [[Anomeric centre (alpha and beta)|anomeric bond]] (often studied using the thio-analogue) shows a dihedral angle φ (O5'-C1'-[O,S]x-Cx) that is in the lowest-energy synclinal (gauche) conformation. The rationale for this is that a minus synclinal dihedral angle φ for an equatorial glycosidic bond, or plus synclinal for an axial glycosidic bond <cite>Perez1978</cite>, allows for hyperconjugative overlap of the C1'-O5' antibonding orbital with an antiperiplanar-oriented lone pair orbital lobe of the glycosidic oxygen, thereby creating partial double bond character and stabilization of the glycosidic bond by 4–5 kcal/mol; this ground-state stabilizing phenomenon is known as the ‘exo-anomeric effect’ <cite>Cramer1997 Johnson2009 Alonso2016</cite>. ''Anti'' [[General_acid/base|protonation]] occurs on the glycosidic oxygen’s antiperiplanar lone pair, thereby removing the stabilizing exo-anomeric effect. This suggests that ''anti'' [[General_acid/base|protonation]] is an enzymic approach for lowering the activation barrier leading to the [[Transition state|transition state]] (Figure 1 centre).

''Syn'' [[General_acid/base|protonating]] [[glycoside hydrolase]]s apparently make use of a different approach <cite>Nerinckx2005 Wu2012</cite>. In many [[Sub-site nomenclature|–1/+1 subsite]]-spanning ligand complexes, the dihedral angle φ of the scissile anomeric bond has been rotated away from its lowest-energy synclinal position: clockwise to minus-anticlinal or antiperiplanar for beta-equatorial; counterclockwise to plus-anticlinal or antiperiplanar for alpha-axial [[Anomeric centre (alpha and beta)|anomeric bonds]]. This removes the hyperconjugative overlap and thus also the stabilizing exo-anomeric effect. And because of this rotation, a lone pair of the glycosidic oxygen is directed into the ''syn'' half-space, allowing it to be protonated by the ''syn''-positioned [[General_acid/base|proton donor]] (Figure 1 right).

[[File:Syn_anti.jpg|800px|thumb|center|Figure 1. Newman projections, with the glycosidic oxygen as proximal atom and the anomeric carbon as distal atom, showing ''anti'' (centre) versus ''syn'' (right) semi-lateral [[General_acid/base|protonation]] in beta-equatorial (top) and alpha-axial (bottom) [[glycoside hydrolase]]s. The indicated φ is the dihedral angle for O5'-C1'-O4-C4.]]

== Table of ''syn/anti'' protonation examples ==

This table contains only one example per GH [[Families|family]] of a ligand-complexed protein structure where the ''syn'' or ''anti'' positioning of the [[General_acid/base|proton donor]] can be clearly observed; other examples may be available on a [[Families|family-by-family]] basis. The reader is thus advised to consult the [http://www.cazy.org/fam/acc_GH.html#table CAZy database] for a current, comprehensive list of CAZyme structures. Where available, the selected examples are Michaelis-type complexes with the ligand spanning the [[Sub-site nomenclature|-1/+1 subsites]], since these have an intact glycosidic or thioglycosidic bond, or are ''N''-analogs of the substrate (''e.g.'' acarbose). In some examples, the [[General_acid/base|proton donor]] has been mutated (''e.g.'', to the corresponding amide or to an alanine), and in those cases one may wish to look at a superposition of the given PDB example with the structure of the native enzyme. If a Michaelis-type complex is not yet available, the second and third example choices, respectively, are trapped glycosyl-enzyme [[intermediate]]s and product complexes where [[Sub-site nomenclature|subsite -1]] is occupied.

''Please also be aware that this is a large table with many data. Please contact the page Author or Responsible Curator with corrections.''

=== Table ===
This table can be re-sorted by clicking on the icons in the header (''javascript must be turned on in your browser''). To reset the page to be sorted by GH family, click the ''View'' tab at the very top of the page.

{| {{Prettytable}} class="sortable"
|- valign="top"
! '''Family'''
! '''Clan'''
! '''Structure fold '''
! '''Anomeric specificity'''
! '''Mechanism'''
! '''''Syn/anti'' protonator'''
! '''Example PDB ID'''
! '''Enzyme'''
! '''Organism'''
! '''Ligand'''
! '''General acid'''
! '''Nucleophile or General base'''
! '''Reference'''
|-
| [[GH1]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2cer 2cer]
| β-glycosidase S
| ''Sulfolobus solfataricus'' P2
| phenethyl glucoimidazole
| '''Glu206'''
| Glu387
| <cite>Gloster2006</cite>
|-
| [[GH2]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vzu 2vzu]
| exo-β-glucosaminidase
| ''Amicolatopsis orientalis''
| PNP-β-{{Smallcaps|d}}-glucosamine
| '''Glu469'''
| Glu541
| <cite>van_Bueren2009</cite>
|-
| [[GH3]]
| none
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1iex 1iex]
| exo-1,3-1,4-glucanase
| ''Hordeum vulgare''
| thiocellobiose
| '''Glu491'''
| Asp285
| <cite>Hrmova2001</cite>
|-
| [[GH5]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1h2j 1h2j]
| endo-β-1,4-glucanase
| ''Bacillus agaradhaerens''
| 2',4'-DNP-2-F-cellobioside
| '''Glu129'''
| Glu228
| <cite>Varrot2003</cite>
|-
| [[GH6]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1qjw 1qjw]
| cellobiohydrolase 2
| ''Hypocrea jecorina''
| (Glc)2-S-(Glc)2
| '''Asp221'''
| debated
| <cite>Zhou1999</cite>
|-
| [[GH7]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1ovw 1ovw]
| endo-1,4-glucanase
| ''Fusarium oxysporum''
| thio-(Glc)5
| '''Glu202'''
| Glu197
| <cite>Sulzenbacher1999</cite>
|-
| [[GH8]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1kwf 1kwf]
| endo-1,4-glucanase
| ''Clostridium thermocellum''
| cellopentaose
| '''Glu95'''
| Asp278
| <cite>Guerin2002</cite>
|-
| [[GH9]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1rq5 1rq5]
| cellobiohydrolase
| ''Clostridium thermocellum''
| cellotetraose
| '''Glu795'''
| Asp383
| <cite>Schubot2004</cite>
|-
| [[GH10]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2d24 2d24]
| β-1,4-xylanase
| ''Streptomyces olivaceoviridis'' E-86
| xylopentaose
| '''Glu128'''
| Glu236
| <cite>Suzuki2009</cite>
|-
| [[GH11]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}4hk8 4hk8]
| endo-β-1,4-xylanase
| ''Hypocrea jecorina''
| xylohexaose
| '''Glu177'''
| Glu86
| <cite>Wan2014</cite>
|-
| [[GH12]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1w2u 1w2u]
| endoglucanase
| ''Humicola grisea''
| thiocellotetraose
| '''Glu205'''
| Glu120
| <cite>Sandgren2004</cite>
|-
| [[GH13]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1cxk 1cxk]
| β-cyclodextrin glucanotransferase
| ''Bacillus circulans''
| maltononaose
| '''Glu257'''
| Asp229
| <cite>Uitdehaag1999</cite>
|-
| [[GH14]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1itc 1itc]
| β-amylase
| ''Bacillus cereus''
| maltopentaose
| '''Glu172'''
| Glu367
| <cite>Miyake2003</cite>
|-
| [[GH15]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1dog 1dog]
| glucoamylase
| ''Aspergillus awamori''
| 1-deoxynojirimycin
| '''Glu179'''
| Glu400
| <cite>Harris1993</cite>
|-
| [[GH16]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1urx 1urx]
| β-agarase A
| ''Zobellia galactanivorans''
| oligoagarose
| '''Glu152'''
| Glu147
| <cite>Allouch2004</cite>
|-
| [[GH17]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzj 4gzj]
| endo-β-1,3-glucanase
| ''Solanum tuberosum''
| laminaratriose + laminarabiose
| '''Glu118'''
| Glu259
| <cite>Wojtkowiak2013</cite>
|-
| [[GH18]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1ffr 1ffr]
| chitinase A
| ''Serratia marcescens''
| (NAG)6
| '''Glu315'''
| internal
| <cite>Papanikolau2001</cite>
|-
| [[GH19]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}3wh1 3wh1]
| chitinase
| ''Bryum coronatum''
| (GlcNAc)4
| '''Glu61'''
| Glu70
| <cite>Ohnuma2014</cite>
|-
| [[GH20]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1c7s 1c7s]
| chitobiase
| ''Serratia marcescens''
| chitobiose
| '''Glu540'''
| internal
| <cite>Prag2000</cite>
|-
| [[GH22]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1h6m 1h6m]
| lysozyme C
| ''Gallus gallus''
| Chit-2-F-chitosyl
| '''Glu35'''
| Asp52
| <cite>Vocadlo2001</cite>
|-
| [[GH23]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1lsp 1lsp]
| lysozyme G
| ''Cygnus atratus''
| Bulgecin A
| '''Glu73'''
| internal
| <cite>Karlsen1996</cite>
|-
| [[GH24]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}148l 148l]
| lysozyme E
| Bacteriophage T4
| chitobiosyl
| '''Glu11'''
| Glu26
| <cite>Baldwin1993</cite>
|-
| [[GH26]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vx6 2vx6]
| exo-β-mannanase
| ''Cellvibrio japonicus'' Ueda107
| Gal1Man4
| '''Glu221'''
| Glu338
| <cite>Cartmell2008</cite>
|-
| [[GH27]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}} / beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3lrm 3lrm]
| α-galactosidase
| ''Saccharomyces cerevisiae''
| raffinose
| '''Asp209'''
| Asp141
| <cite>Fernandez-Leiro2010</cite>
|-
| [[GH28]]
| N
| β-helix
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}2uvf 2uvf]
| exo-polygalacturonosidase
| ''Yersinia enterocolitica'' ATCC9610D
| digalacturonic acid
| '''Asp402'''
| Asp381 Asp403
| <cite>Abbott2007</cite>
|-
| [[GH29]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| '''''syn'''''
| [{{PDBlink}}3uet 3uet]
| α-1,3/4-fucosidase
| ''Bifidobacterium longum'' subsp. infantis
| lacto-''N''-fucopentaose II
| '''Glu217'''
| Asp172
| <cite>Sakurama2012</cite>
|-
| [[GH30]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2y24 2y24]
| glucurono-xylanase
| ''Dickea chrysanthemi'' D1
| glucuronoxylan tetrasaccharide
| '''Glu163'''
| Glu253
| <cite>Urbanikova2011</cite>
|-
| [[GH31]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2qmj 2qmj]
| maltase-glucoamylase
| ''Homo sapiens''
| acarbose
| '''Asp542'''
| Asp443
| <cite>Sim2008</cite>
|-
| [[GH32]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2add 2add]
| fructan β-(2,1)-fructosidase
| ''Cichorium intybus''
| sucrose
| '''Glu201'''
| Asp22
| <cite>Verhaest2007</cite>
|-
| [[GH33]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1s0i 1s0i]
| transsialidase
| ''Trypanosoma cruzi''
| sialyllactose
| '''Asp59'''
| Tyr342
| <cite>Amaya2004</cite>
|-
| [[GH34]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzw 4gzw]
| N2 neuraminidase
| ''Influenza'' A Tanzania/205/2010 H3N2
| α-{{Smallcaps|d}}-Neup5Ac-(2,3)-β-{{Smallcaps|d}}-Galp-(1,4)-β-{{Smallcaps|d}}-GlcpNAc
| '''Asp151'''
| Tyr406
| <cite>Zhu2012</cite>
|-
| [[GH35]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3ogv 3ogv]
| β-galactosidase
| ''Hypocrea jecorina''
| 2-phenylethyl 1-thio-β-{{Smallcaps|d}}-galactopyranoside
| '''Glu200'''
| Glu298
| <cite>Maksimainen2011</cite>
|-
| [[GH36]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4fns 4fns]
| β-galactosidase
| ''Geobacillus stearothermophilus''
| 1-deoxy galactonojirimycin
| '''Asp584'''
| Asp478
| <cite>Merceron2012</cite>
|-
| [[GH37]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2jf4 2jf4]
| trehalase
| ''Escherichia coli''
| validoxylamine
| '''Asp312'''
| Glu496
| <cite>Gibson2007</cite>
|-
| [[GH38]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3czn 3czn]
| Golgi α-mannosidase II
| ''Drosophila melanogaster''
| GlcNAcMan(5)GlcNAc(2)
| '''Asp341'''
| Asp204
| <cite>Shah2008</cite>
|-
| [[GH39]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2bfg 2bfg]
| β-xylosidase
| ''Geobacillus stearothermophilus''
| 2,5-dinitrophenyl-β-{{Smallcaps|d}}-xyloside
| '''Glu160'''
| Glu278
| <cite>Czjzek2005</cite>
|-
| [[GH42]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ucf 4ucf]
| β-galactosidase
| ''Bifidobacterium bifidum''
| {{Smallcaps|d}}-galactose
| '''Glu161'''
| Glu320
| <cite>Godoy2016</cite>
|-
| [[GH43]]
| F
| 5-fold β-propeller
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3akh 3akh]
| exo-1,5-α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces avermitilis''
| α-1,5-arabinofuranotriose
| '''Glu196'''
| Asp220
| <cite>Fujimoto2010</cite>
|-
| [[GH44]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2eqd 2eqd]
| endoglucanase
| ''Clostridium thermocellum''
| cellooctaose
| '''Glu186'''
| Glu359
| <cite>Kitago2007</cite>
|-
| [[GH45]]
| none
| 6-stranded β-barrel
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4eng 4eng]
| endo-1,4-glucanase
| ''Humicola insolens''
| cellohexaose
| '''Asp121'''
| Asp10
| <cite>Davies1996</cite>
|-
| [[GH46]]
| I
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4olt 4olt]
| chitosanase
| ''Microbacterium sp.'' OU01
| hexa-glucosamine
| '''Glu25'''
| Asp43
| <cite>Lyu2014</cite>
|-
| [[GH47]]
| none
| (α/α)7
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1x9d 1x9d]
| α-mannosidase I
| ''Homo sapiens''
| Me-2-S-(α-Man)-2-thio-α-Man
| '''Asp463'''
| Glu599
| <cite>Karaveg2005</cite>, <cite>Nerinckx2008</cite>
|-
| [[GH48]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH8''
|
|
|
|
|
|
|-
| [[GH49]]
| N
| β-helix
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH28''
|
|
|
|
|
|
|-
| [[GH50]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4bq5 4bq5]
| exo-β-agarase
| ''Saccharophagus degradans''
| neoagarotetraose
| '''Glu535'''
| Glu695
| <cite>Pluvinage2013</cite>
|-
| [[GH51]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1qw9 1qw9]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Geobacillus stearothermophilus''
| PNP-{{Smallcaps|l}}-arabinofuranoside
| '''Glu175'''
| Glu294
| <cite>Hoevel2003</cite>
|-
| [[GH52]]
| O
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4c1p 4c1p]
| β-xylosidase
| ''Geobacillus thermoglucosidasius''
| xylobiose
| '''Asp517'''
| Glu537
| <cite>Espina2014</cite>
|-
| [[GH53]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2ccr 2ccr]
| β-1,4-galactanase
| ''Bacillus licheniformis''
| galactotriose
| '''Glu165'''
| Glu263
| <cite>Le_Nours2009</cite>
|-
| [[GH54]]
| none
| β-sandwich
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1wd4 1wd4]
| α-{{Smallcaps|l}}-arabinofuranosidase B
| ''Aspergillus kawachii''
| {{Smallcaps|l}}-arabinofuranose
| '''Asp297'''
| Glu221
| <cite>Miyanaga2004</cite>
|-
| [[GH55]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4tz5 4tz5]
| exo-β-1,3-glucanase
| ''Streptomyces sp.'' SirexAA-E
| laminarihexaose
| '''Glu502'''
| unknown
| <cite>Bianchetti2015</cite>
|-
| [[GH56]]
| none
| (β/α)7
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1fcv 1fcv]
| hyaluronidase
| ''Apis mellifera''
| (hyaluron.)4
| '''Glu113'''
| internal
| <cite>Markovic-Housley2000</cite>
|-
| [[GH57]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1k1y 1k1y]
| glucanotransferase
| ''Thermococcus litoralis''
| acarbose
| '''Asp214'''
| Glu123
| <cite>Imamura2003</cite>
|-
| [[GH59]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ccc 4ccc]
| β-galactocerebrosidase
| ''Mus musculus''
| PNP-β-{{Smallcaps|d}}-galactoside
| '''Glu182'''
| Glu258
| <cite>Hill2013</cite>
|-
| [[GH62]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3wn0 3wn0]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces coelicolor''
| β-{{Smallcaps|l}}-Arabinofuranose
| '''Glu361'''
| Asp202
| <cite>Maehara2014</cite>
|-
| [[GH63]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5ca3 5ca3]
| α-glucosidase
| ''Escherichia coli''
| glucose and lactose
| '''Asp501'''
| Glu727
| <cite>Miyazaki2016</cite>
|-
| [[GH65]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}4ktr 4ktr]
| 2-O-α-glucosylglycerol phosphorylase
| ''Bacillus selenitireducens''
| isofagomine
| '''Glu475'''
| phosphate
| <cite>Touhara2014</cite>
|-
| [[GH66]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5axh 5axh]
| dextranase
| ''Thermoanaerobacter pseudethanolicus''
| isomaltohexaose
| '''Glu374'''
| Asp312
| <cite>Suzuki2016</cite>
|-
| [[GH67]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1l8n 1l8n]
| α-glucuronidase
| ''Geobacillus stearothermophilus''
| 4-O-methyl-{{Smallcaps|d}}-glucuronic acid and xylotriose
| '''Glu286'''
| Asp364 Glu392
| <cite>Golan2004</cite>
|-
| [[GH68]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1pt2 1pt2]
| levansucrase
| ''Bacillus subtilis''
| sucrose
| '''Glu342'''
| Asp86
| <cite>Meng2003</cite>
|-
| [[GH70]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3aic 3aic]
| glucansucrase
| ''Streptococcus mutans''
| α-acarbose
| '''Glu515'''
| Asp477
| <cite>Ito2011</cite>
|-
| [[GH72]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w62 2w62]
| β-1,3-glucanotransferase
| ''Saccharomyces cerevisiae'' S288C
| laminaripentaose
| '''Glu176'''
| Glu275
| <cite>Hurtado-Gerrero2009</cite>
|-
| [[GH74]]
| none
| 7-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}2ebs 2ebs]
| cellobiohydrolase (OXG-RCBH)
| ''Geotrichum sp.'' m128
| xyloglucan heptasaccharide
| '''Asp465'''
| Asp35
| <cite>Yaoi2007</cite>
|-
| [[GH76]]
| none
| (α/α)6
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5agd 5agd]
| endo-α-1,6-mannanase
| ''Bacillus circulans''
| α-1,6-mannopentaose
| '''Asp125'''
| Asp124
| <cite>Thompson2015</cite>
|-
| [[GH77]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2oww 2oww]
| 4-α-glucanotransferase
| ''Thermus thermofilus''
| acarbose + 4-deoxy-α-{{Smallcaps|d}}-glucose
| '''Glu340'''
| Asp293
| <cite>Barends2007</cite>
|-
| [[GH78]]
| H
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3w5n 3w5n]
| α-{{Smallcaps|l}}-rhamnosidase
| ''Streptomyces avermitilis''
| {{Smallcaps|l}}-rhamnose
| '''Glu636'''
| Glu895
| <cite>Fujimoto2013</cite>
|-
| [[GH79]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5e9c 5e9c]
| heparanase
| ''Homo sapiens''
| heparin tetrasaccharide
| '''Glu225'''
| Glu343
| <cite>Wu2015</cite>
|-
| [[GH80]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH24''
|
|
|
|
|
|
|-
| [[GH81]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5t4g 5t4g]
| endo-β-1,3-glucanase
| ''Bacillus halodurans'' C-125
| laminarin
| '''Asp466'''
| Glu542
| <cite>Pluvinage2017</cite>
|-
| [[GH83]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1z4x 1z4x]
| hemagglutinin-neuraminidase
| Simian virus 5
| α-2,3-sialyllactose
| '''Glu247''' relay
| Tyr523
| <cite>Yuan2005</cite>
|-
| [[GH84]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2chn 2chn]
| β-''N''-acetyl-glucosaminidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| NAG-thiazoline
| '''Glu242'''
| internal
| <cite>Dennis2006</cite>
|-
| [[GH85]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w92 2w92]
| endo-β-''N''-acetyl-glucosaminidase D
| ''Streptococcus pneumoniae'' TIGR4
| NAG-thiazoline
| '''Glu337'''
| internal
| <cite>Abbott2009</cite>
|-
| [[GH86]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4aw7 4aw7]
| β-porphyranase
| ''Bacteroides plebeius''
| porphyran fragment
| '''Glu152'''
| Glu279
| <cite>Hehemann_1_2012</cite>
|-
| [[GH89]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vcb 2vcb]
| α-''N''-acetyl-glucosaminidase
| ''Clostridium perfringens''
| PUGNAc
| '''Glu483'''
| Glu601
| <cite>Ficko-Blean2008</cite>
|-
| [[GH92]]
| none
| (α/α)6 and β-sandwich
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ww1 2ww1]
| α-1,2-mannosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| thiomannobioside
| '''Glu533'''
| Asp644 Asp642
| <cite>Zhu2009</cite>
|-
| [[GH93]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3a72 3a72]
| exo-arabinanase
| ''Penicillium chrysogenum''
| arabinobiose
| '''Glu246'''
| Glu174
| <cite>Sogabe2011</cite>
|-
| [[GH94]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4zli 4zli]
| cellobionic acid phosphorylase
| ''Saccharophagus degradans''
| 3-O-β-{{Smallcaps|d}}-glucopyranosyl-α-{{Smallcaps|d}}-glucopyranuronic acid
| '''Asp472'''
| phosphate
| <cite>Nam2015</cite>
|-
| [[GH95]]
| none
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ead 2ead]
| α-1,2-{{Smallcaps|l}}-fucosidase
| ''Bifidobacterium bifidum''
| Fuc-α-1,2-Gal
| '''Glu566'''
| Asn423 Asp766
| <cite>Nagae2007</cite>
|-
| [[GH97]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining + inverting
| '''''anti'''''
| [{{PDBlink}}2zq0 2zq0]
| α-glucosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| acarbose
| '''Glu532'''
| Glu508
| <cite>Kitamura2008</cite>
|-
| [[GH98]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2wmg 2wmg]
| endo-β-1,4-galactosidase
| ''Streptococcus pneumoniae''
| A-LewisY pentasaccharide
| '''Glu158'''
| Asp251 Glu301
| <cite>Higgins2009</cite>
|-
| [[GH99]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ad4 4ad4]
| endo-α-mannosidase
| ''Bacteroides xylanisolvens''
| glucose-1,3-isofagomine and α-1,2- mannobiose
| '''Glu336'''
| debated
| <cite>Thompson2012</cite>
|-
| [[GH100]]
| none
| (α/α)6 core
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5gop 5gop]
| invertase
| ''Anabaena (Nostoc) sp.'' pcc7120
| sucrose
| '''Asp188'''
| Glu414
| <cite>Xie2016</cite>
|-
| [[GH102]]
| none
| double-ψ β-barrel
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}2pi8 2pi8]
| lytic transglycosylase A
| ''Escherichia coli''
| chitohexaose
| '''Asp308'''
| none
| <cite>van_Straaten2007</cite>
|-
| [[GH103]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1d0k 1d0k]
| lytic transglycosylase SLT35
| ''Escherichia coli''
| murodipeptides
| '''Glu162'''
| internal
| <cite>van_Asselt2000</cite>
|-
| [[GH106]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5mwk 5mwk]
| α-{{Smallcaps|l}}-rhamnosidase BT_0986
| ''Bacteroides thetaiotaomicron''
| pectin heptasaccharide
| '''Glu461'''
| Glu593 or Glu561
| <cite>Ndeh2017</cite>
|-
| [[GH107]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| ''predicted syn by clan''
| ''see at GH29''
|
|
|
|
|
|
|-
| [[GH113]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4cd8 4cd8]
| β-mannanase
| ''Alicyclobacillus acidocaldarius''
| mannobioimidazole
| '''Glu151'''
| Glu231
| <cite>Williams2014</cite>
|-
| [[GH116]]
| O
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at GH52''
|
|
|
|
|
|
|-
| [[GH117]]
| none
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}4ak7 4ak7]
| α-1,3-3,6-anhydro-{{Smallcaps|l}}-galactosidase
| ''Bacteroides plebeius''
| neoagarobiose
| '''His302'''
| Asp90
| <cite>Hehemann_2_2012</cite>
|-
| [[GH120]]
| none
| parallel β-helix and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3vsv 3vsv]
| β-xylosidase XylC
| ''Thermoanaerobacterium saccharolyticum'' JW/SL-YS485
| {{Smallcaps|d}}-xylose
| '''Glu405'''
| Asp382
| <cite>Huang2012</cite>
|-
| [[GH123]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5fr0 5fr0]
| exo-β-N-acetyl-galactosaminidase
| ''Clostridium perfringens''
| ''N''-difluoroacetyl-{{Smallcaps|d}}-galactosamine
| '''Glu345'''
| internal
| <cite>Noach2016</cite>
|-
| [[GH125]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5m7y 5m7y]
| exo-α-1,6-mannosidase
| ''Clostridium perfringens''
| 1,6-α-mannotriose
| '''Asp220'''
| Glu393
| <cite>Alonso-Gil2016</cite>
|-
| [[GH127]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3wrg 3wrg]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bifidobacterium longum''
| {{Smallcaps|l}}-arabinose
| '''Glu322'''
| Cys417
| <cite>Huang2014</cite>
|-
| [[GH128]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH1''
|
|
|
|
|
|
|-
| [[GH130]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5b0s 5b0s]
| β-1,2-mannobiose phosphorylase
| ''Listeria innocua''
| β-1,2-mannotriose
| '''Asp141''' relay
| phosphate
| <cite>Tsuda2015</cite>
|-
| [[GH134]]
| none
| β + α
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5jug 5jug]
| β-mannanase
| ''Streptomyces sp.''
| mannopentaose
| '''Glu45'''
| Asp57
| <cite>Jin2016</cite>
|-
| [[GH136]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}5gqf 5gqf]
| lacto-N-biosidase
| ''Bifidobacterium longum''
| lacto-N-biose
| '''Asp411'''
| Asp418
| <cite>Yamada2017</cite>
|-
| [[GH137]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|l}}
| unknown
| '''''anti'''''
| [{{PDBlink}}5mui 5mui]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0996
| ''Bacteroides thetaiotaomicron''
| pectin oligosaccharide
| '''Glu240'''
| Glu159
| <cite>Ndeh2017</cite>

|-
| [[GH138]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}6hzg 6hzg]
| α-1,2-{{Smallcaps|d}}-galacturonidase
| ''Bacteroides paurosaccharolyticus''
| alpha-{{Smallcaps|d}}-galactopyranuronic
| '''Glu294'''
| Glu361
| <cite>Labourel2019</cite>
|-
| [[GH146]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5opj 5opj]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0349
| ''Bacteroides thetaiotaomicron''
| {{Smallcaps|l}}-arabinose
| '''Glu320'''
| Cys416
| <cite>Luis2018</cite>
|-
| [[GH147]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH148]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH149]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH157]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH158]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH161]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH162]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}6imw 5imw]
| endo-β-1,2-glucanase
| ''Talaromyces funiculosus''
| beta-1,2-glucan
| '''Glu262'''
| Asp446
| <cite>Tanaka2019</cite>
|-
| [http://www.cazy.org/GH0.html n.c.*]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2vjj 2vjj]
| endo-α-N-acetylglucosaminidase
| Bacteriophage HK620
| O18A1 O-antigen hexasaccharide
| '''Asp339'''
| Glu372
| <cite>Barbirz2008</cite>
|}
<nowiki>*</nowiki> n.c.: Found among the collection of [http://www.cazy.org/GH0.html non-classified GH sequences in the CAZy Database].

== References ==

<biblio>
# HeightmanVasella1999 Heightman TD and Vasella AT. ''Recent Insights into Inhibition, Structure, and Mechanism of Configuration-Retaining Glycosidases.'' Angew Chem Int Ed. 1999 38(6):750-770. [http://www3.interscience.wiley.com/journal/55000581/abstract Article online].
# Nerinckx2005 pmid=15642336
# Wu2012 pmid=23137336
# Perez1978 Pérez S and Marchessault RH. ''The exo-anomeric effect: experimental evidence from crystal structures.'' Carbohydr res. 1978 65:114-120. [http://dx.doi.org/10.1016/S0008-6215(00)84218-4 DOI:10.1016/S0008-6215(00)84218-4]
# Cramer1997 Cramer CJ, Truhlar DG, and French AD. ''Exo-anomeric effects on energies and geometries of different conformations of glucose and related systems in the gas phase and aqueous solution.'' Carbohydr res. 1997 298:1-14. [http://dx.doi.org/10.1016/S0008-6215(96)00297-2 DOI:10.1016/S0008-6215(96)00297-2]
# Johnson2009 pmid=19733839
# Alonso2016 pmid=26889578
# Gloster2006 pmid=17002288
# van_Bueren2009 pmid=18976664
# Hrmova2001 pmid=11709165
# Varrot2003 pmid=12595701
# Zhou1999 pmid=10508787
# Sulzenbacher1999 pmid=10200171
# Urbanikova2011 pmid=21501386
# Guerin2002 pmid=11884144
# Schubot2004 pmid=14756552
# Suzuki2009 pmid=19279191
# Wan2014 pmid=24419374
# Sandgren2004 pmid=15364577
# Uitdehaag1999 pmid=10331869
# Miyake2003 pmid=12741813
# Harris1993 pmid=8431441
# Allouch2004 pmid=15062085
# Wojtkowiak2013 pmid=23275163
# Papanikolau2001 pmid=11560481
# Prag2000 pmid=10884356
# Vocadlo2001 pmid=11518970
# Karlsen1996 pmid=15299731
# Baldwin1993 pmid=8259514
# Cartmell2008 pmid=18799462
# Fernandez-Leiro2010 pmid=20592022
# Abbott2007 pmid=17397864
# Sakurama2012 pmid=22451675
# Sim2008 pmid=18036614
# Verhaest2007 pmid=17335500
# Amaya2004 pmid=15130470
# Zhu2012 pmid=23015718
# Maksimainen2011 pmid=21130883
# Merceron2012 pmid=23012371
# Gibson2007 pmid=17455176
# Shah2008 pmid=18599462
# Czjzek2005 pmid=16212978
# Godoy2016 pmid=27685756
# Fujimoto2010 pmid=20739278
# Kitago2007 pmid=17905739
# Davies1996 pmid=15299721
# Lyu2014 pmid=24766439
# Karaveg2005 pmid=15713668
# Nerinckx2008 pmid=18619586
# Pluvinage2013 pmid=23921382

# Yuan2005 pmid=15893670
# Hoevel2003 pmid=14517232
# Espina2014 pmid=24816105
# Le_Nours2009 pmid=19089956
# Miyanaga2004 pmid=15292273
# Bianchetti2015 pmid=25752603
# Markovic-Housley2000 pmid=11080624
# Imamura2003 pmid=12618437
# Hill2013 pmid=24297913

# Maehara2014 pmid=24482228

# Miyazaki2016 pmid=27688023
# Touhara2014 pmid=24828502
# Suzuki2016 pmid=26494689
# Golan2004 pmid=14573597
# Meng2003 pmid=14517548
# Ito2011 pmid=21354427
# Hurtado-Gerrero2009 pmid=19097997
# Yaoi2007 pmid=17498741
# Thompson2015 pmid=25772148
# Barends2007 pmid=17420245
# Fujimoto2013 pmid=23486481
# Wu2015 pmid=26575439
# Pluvinage2017 pmid=28781080
# Dennis2006 pmid=16565725
# Abbott2009 pmid=19181667
# Hehemann_1_2012 pmid=23150581
# Ficko-Blean2008 pmid=18443291
# Zhu2009 pmid=20081828
# Sogabe2011 pmid=21543843
# Nam2015 pmid=26041776
# Nagae2007 pmid=17459873
# Kitamura2008 pmid=18981178
# Higgins2009 pmid=19608744
# van_Straaten2007 pmid=17502382
# van_Asselt2000 pmid=10684641
# Ndeh2017 pmid=28329766
# Labourel2019 pmid=30877196
# Luis2018 pmid=29255254
# Jin2016 Jin Y, Petricevic M, John A, Raich L, Jenkins H, Portela De Souza L, Cuskin F, Gilbert HJ, Rovira C, Goddard-Borger ED, Williams SJ, and Davies GJ. ''A β-Mannanase with a Lysozyme-like Fold and a Novel Molecular Catalytic Mechanism.'' ACS Cent Sci. 2016 Nov [http://dx.doi.org/10.1021/acscentsci.6b00232 DOI:10.1021/acscentsci.6b00232]
# Yamada2017 pmid=28392148
# Ohnuma2014 pmid=24582745
# Thompson2012 pmid=22219371
# Xie2016 pmid=27777307
# Williams2014 pmid=24339341
# Hehemann_2_2012 pmid=22393053
# Huang2012 pmid=22992047
# Noach2016 pmid=27038508
# Alonso-Gil2016 pmid=28026180
# Huang2014 Huang CH, Zhu Z, Cheng YS, Chan HC, Ko TP, Chen CC, Wang I, Ho MR, Hsu ST, Zeng YF, Huang YN, Liu JR, Guo RT. ''Structure and Catalytic Mechanism of a Glycoside Hydrolase Family-127 β-L-Arabinofuranosidase (HypBA1).'' J Bioprocess Biotech. 2014 4:171 [http://dx.doi.org/10.4172/2155-9821.1000171 DOI:10.4172/2155-9821.1000171]
# Tsuda2015 pmid=26632508
# Barbirz2008 pmid=18547389
# Tanaka2019 pmid=30926603

</biblio>

[[Category:Definitions and explanations]]

Syn/anti lateral protonation

2019-05-29T21:13:23Z

Wim Nerinckx: GH83 is anti

{{CuratorApproved}}
* [[Author]]: ^^^Wim Nerinckx^^^
* [[Responsible Curator]]: ^^^Spencer Williams^^^

----

== Overview ==

This page provides a table that summarizes the spatial positioning of the catalytic [[general acid]] residue in the active sites of [[glycoside hydrolase]]s, relative to the substrate. The table below updates those found in the seminal paper on this concept by Heightman and Vasella <cite>HeightmanVasella1999</cite>, and a following paper by Nerinckx ''et al.'' <cite>Nerinckx2005</cite>.

== Background ==

The ''"not from above, but from the side"'' concept of semi-lateral glycosidic oxygen [[General_acid/base|protonation]] by [[glycoside hydrolase]]s was introduced by Heightman and Vasella <cite>HeightmanVasella1999</cite>. It was originally only described for [[Anomeric centre (alpha and beta)|beta]]-equatorial [[glycoside hydrolase]]s, but appears to be equally applicable to enzymes acting on an [[Anomeric centre (alpha and beta)|alpha]]-axial glycosidic bond <cite>Nerinckx2005</cite>. When dividing [[Sub-site nomenclature|subsite -1]] into half-spaces by a plane defined by the glycosidic oxygen and C1' and H1' of the –1 glycoside, many ligand-complexed structures reveal that the [[General_acid/base|proton donor]] is positioned either in the ''syn'' half-space (near the ring-oxygen of the –1 glycoside), or in the ''anti'' half-space (on the opposite side of the ring-oxygen). Members of the same GH [[Families|family]] appear to share a common ''syn'' or ''anti'' [[General_acid/base|protonator]] arrangement and further, this specificity appears to be preserved within [[Clans|Clans]] of [[Families|families]]. This page's compilation of [[Sub-site nomenclature|subsite -1]] occupied complexes shows that about 70% of all GH [[Families|families]] are ''anti'' [[General_acid/base|protonators]].

Closer inspection of crystal structures of [[Sub-site nomenclature|–1/+1 subsite]]-spanning substrates, or substrate-analogue ligands, in complex with enzymes reveals a further intriguing corollary <cite>Nerinckx2005 Wu2012</cite>. In substrate-bound complexes with ''anti'' [[General_acid/base|protonating]] GH enzymes, the scissile [[Anomeric centre (alpha and beta)|anomeric bond]] (often studied using the thio-analogue) shows a dihedral angle φ (O5'-C1'-[O,S]x-Cx) that is in the lowest-energy synclinal (gauche) conformation. The rationale for this is that a minus synclinal dihedral angle φ for an equatorial glycosidic bond, or plus synclinal for an axial glycosidic bond <cite>Perez1978</cite>, allows for hyperconjugative overlap of the C1'-O5' antibonding orbital with an antiperiplanar-oriented lone pair orbital lobe of the glycosidic oxygen, thereby creating partial double bond character and stabilization of the glycosidic bond by 4–5 kcal/mol; this ground-state stabilizing phenomenon is known as the ‘exo-anomeric effect’ <cite>Cramer1997 Johnson2009 Alonso2016</cite>. ''Anti'' [[General_acid/base|protonation]] occurs on the glycosidic oxygen’s antiperiplanar lone pair, thereby removing the stabilizing exo-anomeric effect. This suggests that ''anti'' [[General_acid/base|protonation]] is an enzymic approach for lowering the activation barrier leading to the [[Transition state|transition state]] (Figure 1 centre).

''Syn'' [[General_acid/base|protonating]] [[glycoside hydrolase]]s apparently make use of a different approach <cite>Nerinckx2005 Wu2012</cite>. In many [[Sub-site nomenclature|–1/+1 subsite]]-spanning ligand complexes, the dihedral angle φ of the scissile anomeric bond has been rotated away from its lowest-energy synclinal position: clockwise to minus-anticlinal or antiperiplanar for beta-equatorial; counterclockwise to plus-anticlinal or antiperiplanar for alpha-axial [[Anomeric centre (alpha and beta)|anomeric bonds]]. This removes the hyperconjugative overlap and thus also the stabilizing exo-anomeric effect. And because of this rotation, a lone pair of the glycosidic oxygen is directed into the ''syn'' half-space, allowing it to be protonated by the ''syn''-positioned [[General_acid/base|proton donor]] (Figure 1 right).

[[File:Syn_anti.jpg|800px|thumb|center|Figure 1. Newman projections, with the glycosidic oxygen as proximal atom and the anomeric carbon as distal atom, showing ''anti'' (centre) versus ''syn'' (right) semi-lateral [[General_acid/base|protonation]] in beta-equatorial (top) and alpha-axial (bottom) [[glycoside hydrolase]]s. The indicated φ is the dihedral angle for O5'-C1'-O4-C4.]]

== Table of ''syn/anti'' protonation examples ==

This table contains only one example per GH [[Families|family]] of a ligand-complexed protein structure where the ''syn'' or ''anti'' positioning of the [[General_acid/base|proton donor]] can be clearly observed; other examples may be available on a [[Families|family-by-family]] basis. The reader is thus advised to consult the [http://www.cazy.org/fam/acc_GH.html#table CAZy database] for a current, comprehensive list of CAZyme structures. Where available, the selected examples are Michaelis-type complexes with the ligand spanning the [[Sub-site nomenclature|-1/+1 subsites]], since these have an intact glycosidic or thioglycosidic bond, or are ''N''-analogs of the substrate (''e.g.'' acarbose). In some examples, the [[General_acid/base|proton donor]] has been mutated (''e.g.'', to the corresponding amide or to an alanine), and in those cases one may wish to look at a superposition of the given PDB example with the structure of the native enzyme. If a Michaelis-type complex is not yet available, the second and third example choices, respectively, are trapped glycosyl-enzyme [[intermediate]]s and product complexes where [[Sub-site nomenclature|subsite -1]] is occupied.

''Please also be aware that this is a large table with many data. Please contact the page Author or Responsible Curator with corrections.''

=== Table ===
This table can be re-sorted by clicking on the icons in the header (''javascript must be turned on in your browser''). To reset the page to be sorted by GH family, click the ''View'' tab at the very top of the page.

{| {{Prettytable}} class="sortable"
|- valign="top"
! '''Family'''
! '''Clan'''
! '''Structure fold '''
! '''Anomeric specificity'''
! '''Mechanism'''
! '''''Syn/anti'' protonator'''
! '''Example PDB ID'''
! '''Enzyme'''
! '''Organism'''
! '''Ligand'''
! '''General acid'''
! '''Nucleophile or General base'''
! '''Reference'''
|-
| [[GH1]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2cer 2cer]
| β-glycosidase S
| ''Sulfolobus solfataricus'' P2
| phenethyl glucoimidazole
| '''Glu206'''
| Glu387
| <cite>Gloster2006</cite>
|-
| [[GH2]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vzu 2vzu]
| exo-β-glucosaminidase
| ''Amicolatopsis orientalis''
| PNP-β-{{Smallcaps|d}}-glucosamine
| '''Glu469'''
| Glu541
| <cite>van_Bueren2009</cite>
|-
| [[GH3]]
| none
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1iex 1iex]
| exo-1,3-1,4-glucanase
| ''Hordeum vulgare''
| thiocellobiose
| '''Glu491'''
| Asp285
| <cite>Hrmova2001</cite>
|-
| [[GH5]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1h2j 1h2j]
| endo-β-1,4-glucanase
| ''Bacillus agaradhaerens''
| 2',4'-DNP-2-F-cellobioside
| '''Glu129'''
| Glu228
| <cite>Varrot2003</cite>
|-
| [[GH6]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1qjw 1qjw]
| cellobiohydrolase 2
| ''Hypocrea jecorina''
| (Glc)2-S-(Glc)2
| '''Asp221'''
| debated
| <cite>Zhou1999</cite>
|-
| [[GH7]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1ovw 1ovw]
| endo-1,4-glucanase
| ''Fusarium oxysporum''
| thio-(Glc)5
| '''Glu202'''
| Glu197
| <cite>Sulzenbacher1999</cite>
|-
| [[GH8]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1kwf 1kwf]
| endo-1,4-glucanase
| ''Clostridium thermocellum''
| cellopentaose
| '''Glu95'''
| Asp278
| <cite>Guerin2002</cite>
|-
| [[GH9]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1rq5 1rq5]
| cellobiohydrolase
| ''Clostridium thermocellum''
| cellotetraose
| '''Glu795'''
| Asp383
| <cite>Schubot2004</cite>
|-
| [[GH10]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2d24 2d24]
| β-1,4-xylanase
| ''Streptomyces olivaceoviridis'' E-86
| xylopentaose
| '''Glu128'''
| Glu236
| <cite>Suzuki2009</cite>
|-
| [[GH11]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}4hk8 4hk8]
| endo-β-1,4-xylanase
| ''Hypocrea jecorina''
| xylohexaose
| '''Glu177'''
| Glu86
| <cite>Wan2014</cite>
|-
| [[GH12]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1w2u 1w2u]
| endoglucanase
| ''Humicola grisea''
| thiocellotetraose
| '''Glu205'''
| Glu120
| <cite>Sandgren2004</cite>
|-
| [[GH13]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1cxk 1cxk]
| β-cyclodextrin glucanotransferase
| ''Bacillus circulans''
| maltononaose
| '''Glu257'''
| Asp229
| <cite>Uitdehaag1999</cite>
|-
| [[GH14]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1itc 1itc]
| β-amylase
| ''Bacillus cereus''
| maltopentaose
| '''Glu172'''
| Glu367
| <cite>Miyake2003</cite>
|-
| [[GH15]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1dog 1dog]
| glucoamylase
| ''Aspergillus awamori''
| 1-deoxynojirimycin
| '''Glu179'''
| Glu400
| <cite>Harris1993</cite>
|-
| [[GH16]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1urx 1urx]
| β-agarase A
| ''Zobellia galactanivorans''
| oligoagarose
| '''Glu152'''
| Glu147
| <cite>Allouch2004</cite>
|-
| [[GH17]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzj 4gzj]
| endo-β-1,3-glucanase
| ''Solanum tuberosum''
| laminaratriose + laminarabiose
| '''Glu118'''
| Glu259
| <cite>Wojtkowiak2013</cite>
|-
| [[GH18]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1ffr 1ffr]
| chitinase A
| ''Serratia marcescens''
| (NAG)6
| '''Glu315'''
| internal
| <cite>Papanikolau2001</cite>
|-
| [[GH19]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}3wh1 3wh1]
| chitinase
| ''Bryum coronatum''
| (GlcNAc)4
| '''Glu61'''
| Glu70
| <cite>Ohnuma2014</cite>
|-
| [[GH20]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1c7s 1c7s]
| chitobiase
| ''Serratia marcescens''
| chitobiose
| '''Glu540'''
| internal
| <cite>Prag2000</cite>
|-
| [[GH22]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1h6m 1h6m]
| lysozyme C
| ''Gallus gallus''
| Chit-2-F-chitosyl
| '''Glu35'''
| Asp52
| <cite>Vocadlo2001</cite>
|-
| [[GH23]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1lsp 1lsp]
| lysozyme G
| ''Cygnus atratus''
| Bulgecin A
| '''Glu73'''
| internal
| <cite>Karlsen1996</cite>
|-
| [[GH24]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}148l 148l]
| lysozyme E
| Bacteriophage T4
| chitobiosyl
| '''Glu11'''
| Glu26
| <cite>Baldwin1993</cite>
|-
| [[GH26]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vx6 2vx6]
| exo-β-mannanase
| ''Cellvibrio japonicus'' Ueda107
| Gal1Man4
| '''Glu221'''
| Glu338
| <cite>Cartmell2008</cite>
|-
| [[GH27]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}} / beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3lrm 3lrm]
| α-galactosidase
| ''Saccharomyces cerevisiae''
| raffinose
| '''Asp209'''
| Asp141
| <cite>Fernandez-Leiro2010</cite>
|-
| [[GH28]]
| N
| β-helix
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}2uvf 2uvf]
| exo-polygalacturonosidase
| ''Yersinia enterocolitica'' ATCC9610D
| digalacturonic acid
| '''Asp402'''
| Asp381 Asp403
| <cite>Abbott2007</cite>
|-
| [[GH29]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| '''''syn'''''
| [{{PDBlink}}3uet 3uet]
| α-1,3/4-fucosidase
| ''Bifidobacterium longum'' subsp. infantis
| lacto-''N''-fucopentaose II
| '''Glu217'''
| Asp172
| <cite>Sakurama2012</cite>
|-
| [[GH30]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2y24 2y24]
| glucurono-xylanase
| ''Dickea chrysanthemi'' D1
| glucuronoxylan tetrasaccharide
| '''Glu163'''
| Glu253
| <cite>Urbanikova2011</cite>
|-
| [[GH31]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2qmj 2qmj]
| maltase-glucoamylase
| ''Homo sapiens''
| acarbose
| '''Asp542'''
| Asp443
| <cite>Sim2008</cite>
|-
| [[GH32]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2add 2add]
| fructan β-(2,1)-fructosidase
| ''Cichorium intybus''
| sucrose
| '''Glu201'''
| Asp22
| <cite>Verhaest2007</cite>
|-
| [[GH33]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1s0i 1s0i]
| transsialidase
| ''Trypanosoma cruzi''
| sialyllactose
| '''Asp59'''
| Tyr342
| <cite>Amaya2004</cite>
|-
| [[GH34]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzw 4gzw]
| N2 neuraminidase
| ''Influenza'' A Tanzania/205/2010 H3N2
| α-{{Smallcaps|d}}-Neup5Ac-(2,3)-β-{{Smallcaps|d}}-Galp-(1,4)-β-{{Smallcaps|d}}-GlcpNAc
| '''Asp151'''
| Tyr406
| <cite>Zhu2012</cite>
|-
| [[GH35]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3ogv 3ogv]
| β-galactosidase
| ''Hypocrea jecorina''
| 2-phenylethyl 1-thio-β-{{Smallcaps|d}}-galactopyranoside
| '''Glu200'''
| Glu298
| <cite>Maksimainen2011</cite>
|-
| [[GH36]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4fns 4fns]
| β-galactosidase
| ''Geobacillus stearothermophilus''
| 1-deoxy galactonojirimycin
| '''Asp584'''
| Asp478
| <cite>Merceron2012</cite>
|-
| [[GH37]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2jf4 2jf4]
| trehalase
| ''Escherichia coli''
| validoxylamine
| '''Asp312'''
| Glu496
| <cite>Gibson2007</cite>
|-
| [[GH38]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3czn 3czn]
| Golgi α-mannosidase II
| ''Drosophila melanogaster''
| GlcNAcMan(5)GlcNAc(2)
| '''Asp341'''
| Asp204
| <cite>Shah2008</cite>
|-
| [[GH39]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2bfg 2bfg]
| β-xylosidase
| ''Geobacillus stearothermophilus''
| 2,5-dinitrophenyl-β-{{Smallcaps|d}}-xyloside
| '''Glu160'''
| Glu278
| <cite>Czjzek2005</cite>
|-
| [[GH42]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ucf 4ucf]
| β-galactosidase
| ''Bifidobacterium bifidum''
| {{Smallcaps|d}}-galactose
| '''Glu161'''
| Glu320
| <cite>Godoy2016</cite>
|-
| [[GH43]]
| F
| 5-fold β-propeller
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3akh 3akh]
| exo-1,5-α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces avermitilis''
| α-1,5-arabinofuranotriose
| '''Glu196'''
| Asp220
| <cite>Fujimoto2010</cite>
|-
| [[GH44]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2eqd 2eqd]
| endoglucanase
| ''Clostridium thermocellum''
| cellooctaose
| '''Glu186'''
| Glu359
| <cite>Kitago2007</cite>
|-
| [[GH45]]
| none
| 6-stranded β-barrel
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4eng 4eng]
| endo-1,4-glucanase
| ''Humicola insolens''
| cellohexaose
| '''Asp121'''
| Asp10
| <cite>Davies1996</cite>
|-
| [[GH46]]
| I
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4olt 4olt]
| chitosanase
| ''Microbacterium sp.'' OU01
| hexa-glucosamine
| '''Glu25'''
| Asp43
| <cite>Lyu2014</cite>
|-
| [[GH47]]
| none
| (α/α)7
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1x9d 1x9d]
| α-mannosidase I
| ''Homo sapiens''
| Me-2-S-(α-Man)-2-thio-α-Man
| '''Asp463'''
| Glu599
| <cite>Karaveg2005</cite>, <cite>Nerinckx2008</cite>
|-
| [[GH48]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH8''
|
|
|
|
|
|
|-
| [[GH49]]
| N
| β-helix
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH28''
|
|
|
|
|
|
|-
| [[GH50]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4bq5 4bq5]
| exo-β-agarase
| ''Saccharophagus degradans''
| neoagarotetraose
| '''Glu535'''
| Glu695
| <cite>Pluvinage2013</cite>
|-
| [[GH51]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1qw9 1qw9]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Geobacillus stearothermophilus''
| PNP-{{Smallcaps|l}}-arabinofuranoside
| '''Glu175'''
| Glu294
| <cite>Hoevel2003</cite>
|-
| [[GH52]]
| O
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4c1p 4c1p]
| β-xylosidase
| ''Geobacillus thermoglucosidasius''
| xylobiose
| '''Asp517'''
| Glu537
| <cite>Espina2014</cite>
|-
| [[GH53]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2ccr 2ccr]
| β-1,4-galactanase
| ''Bacillus licheniformis''
| galactotriose
| '''Glu165'''
| Glu263
| <cite>Le_Nours2009</cite>
|-
| [[GH54]]
| none
| β-sandwich
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1wd4 1wd4]
| α-{{Smallcaps|l}}-arabinofuranosidase B
| ''Aspergillus kawachii''
| {{Smallcaps|l}}-arabinofuranose
| '''Asp297'''
| Glu221
| <cite>Miyanaga2004</cite>
|-
| [[GH55]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4tz5 4tz5]
| exo-β-1,3-glucanase
| ''Streptomyces sp.'' SirexAA-E
| laminarihexaose
| '''Glu502'''
| unknown
| <cite>Bianchetti2015</cite>
|-
| [[GH56]]
| none
| (β/α)7
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1fcv 1fcv]
| hyaluronidase
| ''Apis mellifera''
| (hyaluron.)4
| '''Glu113'''
| internal
| <cite>Markovic-Housley2000</cite>
|-
| [[GH57]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1k1y 1k1y]
| glucanotransferase
| ''Thermococcus litoralis''
| acarbose
| '''Asp214'''
| Glu123
| <cite>Imamura2003</cite>
|-
| [[GH59]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ccc 4ccc]
| β-galactocerebrosidase
| ''Mus musculus''
| PNP-β-{{Smallcaps|d}}-galactoside
| '''Glu182'''
| Glu258
| <cite>Hill2013</cite>
|-
| [[GH62]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3wn0 3wn0]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces coelicolor''
| β-{{Smallcaps|l}}-Arabinofuranose
| '''Glu361'''
| Asp202
| <cite>Maehara2014</cite>
|-
| [[GH63]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5ca3 5ca3]
| α-glucosidase
| ''Escherichia coli''
| glucose and lactose
| '''Asp501'''
| Glu727
| <cite>Miyazaki2016</cite>
|-
| [[GH65]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}4ktr 4ktr]
| 2-O-α-glucosylglycerol phosphorylase
| ''Bacillus selenitireducens''
| isofagomine
| '''Glu475'''
| phosphate
| <cite>Touhara2014</cite>
|-
| [[GH66]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5axh 5axh]
| dextranase
| ''Thermoanaerobacter pseudethanolicus''
| isomaltohexaose
| '''Glu374'''
| Asp312
| <cite>Suzuki2016</cite>
|-
| [[GH67]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1l8n 1l8n]
| α-glucuronidase
| ''Geobacillus stearothermophilus''
| 4-O-methyl-{{Smallcaps|d}}-glucuronic acid and xylotriose
| '''Glu286'''
| Asp364 Glu392
| <cite>Golan2004</cite>
|-
| [[GH68]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1pt2 1pt2]
| levansucrase
| ''Bacillus subtilis''
| sucrose
| '''Glu342'''
| Asp86
| <cite>Meng2003</cite>
|-
| [[GH70]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3aic 3aic]
| glucansucrase
| ''Streptococcus mutans''
| α-acarbose
| '''Glu515'''
| Asp477
| <cite>Ito2011</cite>
|-
| [[GH72]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w62 2w62]
| β-1,3-glucanotransferase
| ''Saccharomyces cerevisiae'' S288C
| laminaripentaose
| '''Glu176'''
| Glu275
| <cite>Hurtado-Gerrero2009</cite>
|-
| [[GH74]]
| none
| 7-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}2ebs 2ebs]
| cellobiohydrolase (OXG-RCBH)
| ''Geotrichum sp.'' m128
| xyloglucan heptasaccharide
| '''Asp465'''
| Asp35
| <cite>Yaoi2007</cite>
|-
| [[GH76]]
| none
| (α/α)6
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5agd 5agd]
| endo-α-1,6-mannanase
| ''Bacillus circulans''
| α-1,6-mannopentaose
| '''Asp125'''
| Asp124
| <cite>Thompson2015</cite>
|-
| [[GH77]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2oww 2oww]
| 4-α-glucanotransferase
| ''Thermus thermofilus''
| acarbose + 4-deoxy-α-{{Smallcaps|d}}-glucose
| '''Glu340'''
| Asp293
| <cite>Barends2007</cite>
|-
| [[GH78]]
| H
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3w5n 3w5n]
| α-{{Smallcaps|l}}-rhamnosidase
| ''Streptomyces avermitilis''
| {{Smallcaps|l}}-rhamnose
| '''Glu636'''
| Glu895
| <cite>Fujimoto2013</cite>
|-
| [[GH79]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5e9c 5e9c]
| heparanase
| ''Homo sapiens''
| heparin tetrasaccharide
| '''Glu225'''
| Glu343
| <cite>Wu2015</cite>
|-
| [[GH80]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH24''
|
|
|
|
|
|
|-
| [[GH81]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5t4g 5t4g]
| endo-β-1,3-glucanase
| ''Bacillus halodurans'' C-125
| laminarin
| '''Asp466'''
| Glu542
| <cite>Pluvinage2017</cite>
|-
| [[GH83]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1x4x 1x4x]
| hemagglutinin-neuraminidase
| Simian virus 5
| α-2,3-sialyllactose
| '''Glu247''' relay
| Tyr523
| <cite>Yuan2005</cite>
|-
| [[GH84]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2chn 2chn]
| β-''N''-acetyl-glucosaminidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| NAG-thiazoline
| '''Glu242'''
| internal
| <cite>Dennis2006</cite>
|-
| [[GH85]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w92 2w92]
| endo-β-''N''-acetyl-glucosaminidase D
| ''Streptococcus pneumoniae'' TIGR4
| NAG-thiazoline
| '''Glu337'''
| internal
| <cite>Abbott2009</cite>
|-
| [[GH86]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4aw7 4aw7]
| β-porphyranase
| ''Bacteroides plebeius''
| porphyran fragment
| '''Glu152'''
| Glu279
| <cite>Hehemann_1_2012</cite>
|-
| [[GH89]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vcb 2vcb]
| α-''N''-acetyl-glucosaminidase
| ''Clostridium perfringens''
| PUGNAc
| '''Glu483'''
| Glu601
| <cite>Ficko-Blean2008</cite>
|-
| [[GH92]]
| none
| (α/α)6 and β-sandwich
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ww1 2ww1]
| α-1,2-mannosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| thiomannobioside
| '''Glu533'''
| Asp644 Asp642
| <cite>Zhu2009</cite>
|-
| [[GH93]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3a72 3a72]
| exo-arabinanase
| ''Penicillium chrysogenum''
| arabinobiose
| '''Glu246'''
| Glu174
| <cite>Sogabe2011</cite>
|-
| [[GH94]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4zli 4zli]
| cellobionic acid phosphorylase
| ''Saccharophagus degradans''
| 3-O-β-{{Smallcaps|d}}-glucopyranosyl-α-{{Smallcaps|d}}-glucopyranuronic acid
| '''Asp472'''
| phosphate
| <cite>Nam2015</cite>
|-
| [[GH95]]
| none
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ead 2ead]
| α-1,2-{{Smallcaps|l}}-fucosidase
| ''Bifidobacterium bifidum''
| Fuc-α-1,2-Gal
| '''Glu566'''
| Asn423 Asp766
| <cite>Nagae2007</cite>
|-
| [[GH97]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining + inverting
| '''''anti'''''
| [{{PDBlink}}2zq0 2zq0]
| α-glucosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| acarbose
| '''Glu532'''
| Glu508
| <cite>Kitamura2008</cite>
|-
| [[GH98]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2wmg 2wmg]
| endo-β-1,4-galactosidase
| ''Streptococcus pneumoniae''
| A-LewisY pentasaccharide
| '''Glu158'''
| Asp251 Glu301
| <cite>Higgins2009</cite>
|-
| [[GH99]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ad4 4ad4]
| endo-α-mannosidase
| ''Bacteroides xylanisolvens''
| glucose-1,3-isofagomine and α-1,2- mannobiose
| '''Glu336'''
| debated
| <cite>Thompson2012</cite>
|-
| [[GH100]]
| none
| (α/α)6 core
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5gop 5gop]
| invertase
| ''Anabaena (Nostoc) sp.'' pcc7120
| sucrose
| '''Asp188'''
| Glu414
| <cite>Xie2016</cite>
|-
| [[GH102]]
| none
| double-ψ β-barrel
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}2pi8 2pi8]
| lytic transglycosylase A
| ''Escherichia coli''
| chitohexaose
| '''Asp308'''
| none
| <cite>van_Straaten2007</cite>
|-
| [[GH103]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1d0k 1d0k]
| lytic transglycosylase SLT35
| ''Escherichia coli''
| murodipeptides
| '''Glu162'''
| internal
| <cite>van_Asselt2000</cite>
|-
| [[GH106]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5mwk 5mwk]
| α-{{Smallcaps|l}}-rhamnosidase BT_0986
| ''Bacteroides thetaiotaomicron''
| pectin heptasaccharide
| '''Glu461'''
| Glu593 or Glu561
| <cite>Ndeh2017</cite>
|-
| [[GH107]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| ''predicted syn by clan''
| ''see at GH29''
|
|
|
|
|
|
|-
| [[GH113]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4cd8 4cd8]
| β-mannanase
| ''Alicyclobacillus acidocaldarius''
| mannobioimidazole
| '''Glu151'''
| Glu231
| <cite>Williams2014</cite>
|-
| [[GH116]]
| O
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at GH52''
|
|
|
|
|
|
|-
| [[GH117]]
| none
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}4ak7 4ak7]
| α-1,3-3,6-anhydro-{{Smallcaps|l}}-galactosidase
| ''Bacteroides plebeius''
| neoagarobiose
| '''His302'''
| Asp90
| <cite>Hehemann_2_2012</cite>
|-
| [[GH120]]
| none
| parallel β-helix and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3vsv 3vsv]
| β-xylosidase XylC
| ''Thermoanaerobacterium saccharolyticum'' JW/SL-YS485
| {{Smallcaps|d}}-xylose
| '''Glu405'''
| Asp382
| <cite>Huang2012</cite>
|-
| [[GH123]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5fr0 5fr0]
| exo-β-N-acetyl-galactosaminidase
| ''Clostridium perfringens''
| ''N''-difluoroacetyl-{{Smallcaps|d}}-galactosamine
| '''Glu345'''
| internal
| <cite>Noach2016</cite>
|-
| [[GH125]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5m7y 5m7y]
| exo-α-1,6-mannosidase
| ''Clostridium perfringens''
| 1,6-α-mannotriose
| '''Asp220'''
| Glu393
| <cite>Alonso-Gil2016</cite>
|-
| [[GH127]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3wrg 3wrg]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bifidobacterium longum''
| {{Smallcaps|l}}-arabinose
| '''Glu322'''
| Cys417
| <cite>Huang2014</cite>
|-
| [[GH128]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH1''
|
|
|
|
|
|
|-
| [[GH130]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5b0s 5b0s]
| β-1,2-mannobiose phosphorylase
| ''Listeria innocua''
| β-1,2-mannotriose
| '''Asp141''' relay
| phosphate
| <cite>Tsuda2015</cite>
|-
| [[GH134]]
| none
| β + α
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5jug 5jug]
| β-mannanase
| ''Streptomyces sp.''
| mannopentaose
| '''Glu45'''
| Asp57
| <cite>Jin2016</cite>
|-
| [[GH136]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}5gqf 5gqf]
| lacto-N-biosidase
| ''Bifidobacterium longum''
| lacto-N-biose
| '''Asp411'''
| Asp418
| <cite>Yamada2017</cite>
|-
| [[GH137]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|l}}
| unknown
| '''''anti'''''
| [{{PDBlink}}5mui 5mui]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0996
| ''Bacteroides thetaiotaomicron''
| pectin oligosaccharide
| '''Glu240'''
| Glu159
| <cite>Ndeh2017</cite>

|-
| [[GH138]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}6hzg 6hzg]
| α-1,2-{{Smallcaps|d}}-galacturonidase
| ''Bacteroides paurosaccharolyticus''
| alpha-{{Smallcaps|d}}-galactopyranuronic
| '''Glu294'''
| Glu361
| <cite>Labourel2019</cite>
|-
| [[GH146]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5opj 5opj]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0349
| ''Bacteroides thetaiotaomicron''
| {{Smallcaps|l}}-arabinose
| '''Glu320'''
| Cys416
| <cite>Luis2018</cite>
|-
| [[GH147]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH148]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH149]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH157]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH158]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH161]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH162]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}6imw 5imw]
| endo-β-1,2-glucanase
| ''Talaromyces funiculosus''
| beta-1,2-glucan
| '''Glu262'''
| Asp446
| <cite>Tanaka2019</cite>
|-
| [http://www.cazy.org/GH0.html n.c.*]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2vjj 2vjj]
| endo-α-N-acetylglucosaminidase
| Bacteriophage HK620
| O18A1 O-antigen hexasaccharide
| '''Asp339'''
| Glu372
| <cite>Barbirz2008</cite>
|}
<nowiki>*</nowiki> n.c.: Found among the collection of [http://www.cazy.org/GH0.html non-classified GH sequences in the CAZy Database].

== References ==

<biblio>
# HeightmanVasella1999 Heightman TD and Vasella AT. ''Recent Insights into Inhibition, Structure, and Mechanism of Configuration-Retaining Glycosidases.'' Angew Chem Int Ed. 1999 38(6):750-770. [http://www3.interscience.wiley.com/journal/55000581/abstract Article online].
# Nerinckx2005 pmid=15642336
# Wu2012 pmid=23137336
# Perez1978 Pérez S and Marchessault RH. ''The exo-anomeric effect: experimental evidence from crystal structures.'' Carbohydr res. 1978 65:114-120. [http://dx.doi.org/10.1016/S0008-6215(00)84218-4 DOI:10.1016/S0008-6215(00)84218-4]
# Cramer1997 Cramer CJ, Truhlar DG, and French AD. ''Exo-anomeric effects on energies and geometries of different conformations of glucose and related systems in the gas phase and aqueous solution.'' Carbohydr res. 1997 298:1-14. [http://dx.doi.org/10.1016/S0008-6215(96)00297-2 DOI:10.1016/S0008-6215(96)00297-2]
# Johnson2009 pmid=19733839
# Alonso2016 pmid=26889578
# Gloster2006 pmid=17002288
# van_Bueren2009 pmid=18976664
# Hrmova2001 pmid=11709165
# Varrot2003 pmid=12595701
# Zhou1999 pmid=10508787
# Sulzenbacher1999 pmid=10200171
# Urbanikova2011 pmid=21501386
# Guerin2002 pmid=11884144
# Schubot2004 pmid=14756552
# Suzuki2009 pmid=19279191
# Wan2014 pmid=24419374
# Sandgren2004 pmid=15364577
# Uitdehaag1999 pmid=10331869
# Miyake2003 pmid=12741813
# Harris1993 pmid=8431441
# Allouch2004 pmid=15062085
# Wojtkowiak2013 pmid=23275163
# Papanikolau2001 pmid=11560481
# Prag2000 pmid=10884356
# Vocadlo2001 pmid=11518970
# Karlsen1996 pmid=15299731
# Baldwin1993 pmid=8259514
# Cartmell2008 pmid=18799462
# Fernandez-Leiro2010 pmid=20592022
# Abbott2007 pmid=17397864
# Sakurama2012 pmid=22451675
# Sim2008 pmid=18036614
# Verhaest2007 pmid=17335500
# Amaya2004 pmid=15130470
# Zhu2012 pmid=23015718
# Maksimainen2011 pmid=21130883
# Merceron2012 pmid=23012371
# Gibson2007 pmid=17455176
# Shah2008 pmid=18599462
# Czjzek2005 pmid=16212978
# Godoy2016 pmid=27685756
# Fujimoto2010 pmid=20739278
# Kitago2007 pmid=17905739
# Davies1996 pmid=15299721
# Lyu2014 pmid=24766439
# Karaveg2005 pmid=15713668
# Nerinckx2008 pmid=18619586
# Pluvinage2013 pmid=23921382

# Yuan2005 pmid=15893670
# Hoevel2003 pmid=14517232
# Espina2014 pmid=24816105
# Le_Nours2009 pmid=19089956
# Miyanaga2004 pmid=15292273
# Bianchetti2015 pmid=25752603
# Markovic-Housley2000 pmid=11080624
# Imamura2003 pmid=12618437
# Hill2013 pmid=24297913

# Maehara2014 pmid=24482228

# Miyazaki2016 pmid=27688023
# Touhara2014 pmid=24828502
# Suzuki2016 pmid=26494689
# Golan2004 pmid=14573597
# Meng2003 pmid=14517548
# Ito2011 pmid=21354427
# Hurtado-Gerrero2009 pmid=19097997
# Yaoi2007 pmid=17498741
# Thompson2015 pmid=25772148
# Barends2007 pmid=17420245
# Fujimoto2013 pmid=23486481
# Wu2015 pmid=26575439
# Pluvinage2017 pmid=28781080
# Dennis2006 pmid=16565725
# Abbott2009 pmid=19181667
# Hehemann_1_2012 pmid=23150581
# Ficko-Blean2008 pmid=18443291
# Zhu2009 pmid=20081828
# Sogabe2011 pmid=21543843
# Nam2015 pmid=26041776
# Nagae2007 pmid=17459873
# Kitamura2008 pmid=18981178
# Higgins2009 pmid=19608744
# van_Straaten2007 pmid=17502382
# van_Asselt2000 pmid=10684641
# Ndeh2017 pmid=28329766
# Labourel2019 pmid=30877196
# Luis2018 pmid=29255254
# Jin2016 Jin Y, Petricevic M, John A, Raich L, Jenkins H, Portela De Souza L, Cuskin F, Gilbert HJ, Rovira C, Goddard-Borger ED, Williams SJ, and Davies GJ. ''A β-Mannanase with a Lysozyme-like Fold and a Novel Molecular Catalytic Mechanism.'' ACS Cent Sci. 2016 Nov [http://dx.doi.org/10.1021/acscentsci.6b00232 DOI:10.1021/acscentsci.6b00232]
# Yamada2017 pmid=28392148
# Ohnuma2014 pmid=24582745
# Thompson2012 pmid=22219371
# Xie2016 pmid=27777307
# Williams2014 pmid=24339341
# Hehemann_2_2012 pmid=22393053
# Huang2012 pmid=22992047
# Noach2016 pmid=27038508
# Alonso-Gil2016 pmid=28026180
# Huang2014 Huang CH, Zhu Z, Cheng YS, Chan HC, Ko TP, Chen CC, Wang I, Ho MR, Hsu ST, Zeng YF, Huang YN, Liu JR, Guo RT. ''Structure and Catalytic Mechanism of a Glycoside Hydrolase Family-127 β-L-Arabinofuranosidase (HypBA1).'' J Bioprocess Biotech. 2014 4:171 [http://dx.doi.org/10.4172/2155-9821.1000171 DOI:10.4172/2155-9821.1000171]
# Tsuda2015 pmid=26632508
# Barbirz2008 pmid=18547389
# Tanaka2019 pmid=30926603

</biblio>

[[Category:Definitions and explanations]]

Syn/anti lateral protonation

2019-05-29T21:07:41Z

Wim Nerinckx: GH62 is anti

{{CuratorApproved}}
* [[Author]]: ^^^Wim Nerinckx^^^
* [[Responsible Curator]]: ^^^Spencer Williams^^^

----

== Overview ==

This page provides a table that summarizes the spatial positioning of the catalytic [[general acid]] residue in the active sites of [[glycoside hydrolase]]s, relative to the substrate. The table below updates those found in the seminal paper on this concept by Heightman and Vasella <cite>HeightmanVasella1999</cite>, and a following paper by Nerinckx ''et al.'' <cite>Nerinckx2005</cite>.

== Background ==

The ''"not from above, but from the side"'' concept of semi-lateral glycosidic oxygen [[General_acid/base|protonation]] by [[glycoside hydrolase]]s was introduced by Heightman and Vasella <cite>HeightmanVasella1999</cite>. It was originally only described for [[Anomeric centre (alpha and beta)|beta]]-equatorial [[glycoside hydrolase]]s, but appears to be equally applicable to enzymes acting on an [[Anomeric centre (alpha and beta)|alpha]]-axial glycosidic bond <cite>Nerinckx2005</cite>. When dividing [[Sub-site nomenclature|subsite -1]] into half-spaces by a plane defined by the glycosidic oxygen and C1' and H1' of the –1 glycoside, many ligand-complexed structures reveal that the [[General_acid/base|proton donor]] is positioned either in the ''syn'' half-space (near the ring-oxygen of the –1 glycoside), or in the ''anti'' half-space (on the opposite side of the ring-oxygen). Members of the same GH [[Families|family]] appear to share a common ''syn'' or ''anti'' [[General_acid/base|protonator]] arrangement and further, this specificity appears to be preserved within [[Clans|Clans]] of [[Families|families]]. This page's compilation of [[Sub-site nomenclature|subsite -1]] occupied complexes shows that about 70% of all GH [[Families|families]] are ''anti'' [[General_acid/base|protonators]].

Closer inspection of crystal structures of [[Sub-site nomenclature|–1/+1 subsite]]-spanning substrates, or substrate-analogue ligands, in complex with enzymes reveals a further intriguing corollary <cite>Nerinckx2005 Wu2012</cite>. In substrate-bound complexes with ''anti'' [[General_acid/base|protonating]] GH enzymes, the scissile [[Anomeric centre (alpha and beta)|anomeric bond]] (often studied using the thio-analogue) shows a dihedral angle φ (O5'-C1'-[O,S]x-Cx) that is in the lowest-energy synclinal (gauche) conformation. The rationale for this is that a minus synclinal dihedral angle φ for an equatorial glycosidic bond, or plus synclinal for an axial glycosidic bond <cite>Perez1978</cite>, allows for hyperconjugative overlap of the C1'-O5' antibonding orbital with an antiperiplanar-oriented lone pair orbital lobe of the glycosidic oxygen, thereby creating partial double bond character and stabilization of the glycosidic bond by 4–5 kcal/mol; this ground-state stabilizing phenomenon is known as the ‘exo-anomeric effect’ <cite>Cramer1997 Johnson2009 Alonso2016</cite>. ''Anti'' [[General_acid/base|protonation]] occurs on the glycosidic oxygen’s antiperiplanar lone pair, thereby removing the stabilizing exo-anomeric effect. This suggests that ''anti'' [[General_acid/base|protonation]] is an enzymic approach for lowering the activation barrier leading to the [[Transition state|transition state]] (Figure 1 centre).

''Syn'' [[General_acid/base|protonating]] [[glycoside hydrolase]]s apparently make use of a different approach <cite>Nerinckx2005 Wu2012</cite>. In many [[Sub-site nomenclature|–1/+1 subsite]]-spanning ligand complexes, the dihedral angle φ of the scissile anomeric bond has been rotated away from its lowest-energy synclinal position: clockwise to minus-anticlinal or antiperiplanar for beta-equatorial; counterclockwise to plus-anticlinal or antiperiplanar for alpha-axial [[Anomeric centre (alpha and beta)|anomeric bonds]]. This removes the hyperconjugative overlap and thus also the stabilizing exo-anomeric effect. And because of this rotation, a lone pair of the glycosidic oxygen is directed into the ''syn'' half-space, allowing it to be protonated by the ''syn''-positioned [[General_acid/base|proton donor]] (Figure 1 right).

[[File:Syn_anti.jpg|800px|thumb|center|Figure 1. Newman projections, with the glycosidic oxygen as proximal atom and the anomeric carbon as distal atom, showing ''anti'' (centre) versus ''syn'' (right) semi-lateral [[General_acid/base|protonation]] in beta-equatorial (top) and alpha-axial (bottom) [[glycoside hydrolase]]s. The indicated φ is the dihedral angle for O5'-C1'-O4-C4.]]

== Table of ''syn/anti'' protonation examples ==

This table contains only one example per GH [[Families|family]] of a ligand-complexed protein structure where the ''syn'' or ''anti'' positioning of the [[General_acid/base|proton donor]] can be clearly observed; other examples may be available on a [[Families|family-by-family]] basis. The reader is thus advised to consult the [http://www.cazy.org/fam/acc_GH.html#table CAZy database] for a current, comprehensive list of CAZyme structures. Where available, the selected examples are Michaelis-type complexes with the ligand spanning the [[Sub-site nomenclature|-1/+1 subsites]], since these have an intact glycosidic or thioglycosidic bond, or are ''N''-analogs of the substrate (''e.g.'' acarbose). In some examples, the [[General_acid/base|proton donor]] has been mutated (''e.g.'', to the corresponding amide or to an alanine), and in those cases one may wish to look at a superposition of the given PDB example with the structure of the native enzyme. If a Michaelis-type complex is not yet available, the second and third example choices, respectively, are trapped glycosyl-enzyme [[intermediate]]s and product complexes where [[Sub-site nomenclature|subsite -1]] is occupied.

''Please also be aware that this is a large table with many data. Please contact the page Author or Responsible Curator with corrections.''

=== Table ===
This table can be re-sorted by clicking on the icons in the header (''javascript must be turned on in your browser''). To reset the page to be sorted by GH family, click the ''View'' tab at the very top of the page.

{| {{Prettytable}} class="sortable"
|- valign="top"
! '''Family'''
! '''Clan'''
! '''Structure fold '''
! '''Anomeric specificity'''
! '''Mechanism'''
! '''''Syn/anti'' protonator'''
! '''Example PDB ID'''
! '''Enzyme'''
! '''Organism'''
! '''Ligand'''
! '''General acid'''
! '''Nucleophile or General base'''
! '''Reference'''
|-
| [[GH1]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2cer 2cer]
| β-glycosidase S
| ''Sulfolobus solfataricus'' P2
| phenethyl glucoimidazole
| '''Glu206'''
| Glu387
| <cite>Gloster2006</cite>
|-
| [[GH2]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vzu 2vzu]
| exo-β-glucosaminidase
| ''Amicolatopsis orientalis''
| PNP-β-{{Smallcaps|d}}-glucosamine
| '''Glu469'''
| Glu541
| <cite>van_Bueren2009</cite>
|-
| [[GH3]]
| none
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1iex 1iex]
| exo-1,3-1,4-glucanase
| ''Hordeum vulgare''
| thiocellobiose
| '''Glu491'''
| Asp285
| <cite>Hrmova2001</cite>
|-
| [[GH5]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1h2j 1h2j]
| endo-β-1,4-glucanase
| ''Bacillus agaradhaerens''
| 2',4'-DNP-2-F-cellobioside
| '''Glu129'''
| Glu228
| <cite>Varrot2003</cite>
|-
| [[GH6]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1qjw 1qjw]
| cellobiohydrolase 2
| ''Hypocrea jecorina''
| (Glc)2-S-(Glc)2
| '''Asp221'''
| debated
| <cite>Zhou1999</cite>
|-
| [[GH7]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1ovw 1ovw]
| endo-1,4-glucanase
| ''Fusarium oxysporum''
| thio-(Glc)5
| '''Glu202'''
| Glu197
| <cite>Sulzenbacher1999</cite>
|-
| [[GH8]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1kwf 1kwf]
| endo-1,4-glucanase
| ''Clostridium thermocellum''
| cellopentaose
| '''Glu95'''
| Asp278
| <cite>Guerin2002</cite>
|-
| [[GH9]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1rq5 1rq5]
| cellobiohydrolase
| ''Clostridium thermocellum''
| cellotetraose
| '''Glu795'''
| Asp383
| <cite>Schubot2004</cite>
|-
| [[GH10]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2d24 2d24]
| β-1,4-xylanase
| ''Streptomyces olivaceoviridis'' E-86
| xylopentaose
| '''Glu128'''
| Glu236
| <cite>Suzuki2009</cite>
|-
| [[GH11]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}4hk8 4hk8]
| endo-β-1,4-xylanase
| ''Hypocrea jecorina''
| xylohexaose
| '''Glu177'''
| Glu86
| <cite>Wan2014</cite>
|-
| [[GH12]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1w2u 1w2u]
| endoglucanase
| ''Humicola grisea''
| thiocellotetraose
| '''Glu205'''
| Glu120
| <cite>Sandgren2004</cite>
|-
| [[GH13]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1cxk 1cxk]
| β-cyclodextrin glucanotransferase
| ''Bacillus circulans''
| maltononaose
| '''Glu257'''
| Asp229
| <cite>Uitdehaag1999</cite>
|-
| [[GH14]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1itc 1itc]
| β-amylase
| ''Bacillus cereus''
| maltopentaose
| '''Glu172'''
| Glu367
| <cite>Miyake2003</cite>
|-
| [[GH15]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1dog 1dog]
| glucoamylase
| ''Aspergillus awamori''
| 1-deoxynojirimycin
| '''Glu179'''
| Glu400
| <cite>Harris1993</cite>
|-
| [[GH16]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1urx 1urx]
| β-agarase A
| ''Zobellia galactanivorans''
| oligoagarose
| '''Glu152'''
| Glu147
| <cite>Allouch2004</cite>
|-
| [[GH17]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzj 4gzj]
| endo-β-1,3-glucanase
| ''Solanum tuberosum''
| laminaratriose + laminarabiose
| '''Glu118'''
| Glu259
| <cite>Wojtkowiak2013</cite>
|-
| [[GH18]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1ffr 1ffr]
| chitinase A
| ''Serratia marcescens''
| (NAG)6
| '''Glu315'''
| internal
| <cite>Papanikolau2001</cite>
|-
| [[GH19]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}3wh1 3wh1]
| chitinase
| ''Bryum coronatum''
| (GlcNAc)4
| '''Glu61'''
| Glu70
| <cite>Ohnuma2014</cite>
|-
| [[GH20]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1c7s 1c7s]
| chitobiase
| ''Serratia marcescens''
| chitobiose
| '''Glu540'''
| internal
| <cite>Prag2000</cite>
|-
| [[GH22]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1h6m 1h6m]
| lysozyme C
| ''Gallus gallus''
| Chit-2-F-chitosyl
| '''Glu35'''
| Asp52
| <cite>Vocadlo2001</cite>
|-
| [[GH23]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1lsp 1lsp]
| lysozyme G
| ''Cygnus atratus''
| Bulgecin A
| '''Glu73'''
| internal
| <cite>Karlsen1996</cite>
|-
| [[GH24]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}148l 148l]
| lysozyme E
| Bacteriophage T4
| chitobiosyl
| '''Glu11'''
| Glu26
| <cite>Baldwin1993</cite>
|-
| [[GH26]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vx6 2vx6]
| exo-β-mannanase
| ''Cellvibrio japonicus'' Ueda107
| Gal1Man4
| '''Glu221'''
| Glu338
| <cite>Cartmell2008</cite>
|-
| [[GH27]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}} / beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3lrm 3lrm]
| α-galactosidase
| ''Saccharomyces cerevisiae''
| raffinose
| '''Asp209'''
| Asp141
| <cite>Fernandez-Leiro2010</cite>
|-
| [[GH28]]
| N
| β-helix
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}2uvf 2uvf]
| exo-polygalacturonosidase
| ''Yersinia enterocolitica'' ATCC9610D
| digalacturonic acid
| '''Asp402'''
| Asp381 Asp403
| <cite>Abbott2007</cite>
|-
| [[GH29]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| '''''syn'''''
| [{{PDBlink}}3uet 3uet]
| α-1,3/4-fucosidase
| ''Bifidobacterium longum'' subsp. infantis
| lacto-''N''-fucopentaose II
| '''Glu217'''
| Asp172
| <cite>Sakurama2012</cite>
|-
| [[GH30]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2y24 2y24]
| glucurono-xylanase
| ''Dickea chrysanthemi'' D1
| glucuronoxylan tetrasaccharide
| '''Glu163'''
| Glu253
| <cite>Urbanikova2011</cite>
|-
| [[GH31]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2qmj 2qmj]
| maltase-glucoamylase
| ''Homo sapiens''
| acarbose
| '''Asp542'''
| Asp443
| <cite>Sim2008</cite>
|-
| [[GH32]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2add 2add]
| fructan β-(2,1)-fructosidase
| ''Cichorium intybus''
| sucrose
| '''Glu201'''
| Asp22
| <cite>Verhaest2007</cite>
|-
| [[GH33]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1s0i 1s0i]
| transsialidase
| ''Trypanosoma cruzi''
| sialyllactose
| '''Asp59'''
| Tyr342
| <cite>Amaya2004</cite>
|-
| [[GH34]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzw 4gzw]
| N2 neuraminidase
| ''Influenza'' A Tanzania/205/2010 H3N2
| α-{{Smallcaps|d}}-Neup5Ac-(2,3)-β-{{Smallcaps|d}}-Galp-(1,4)-β-{{Smallcaps|d}}-GlcpNAc
| '''Asp151'''
| Tyr406
| <cite>Zhu2012</cite>
|-
| [[GH35]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3ogv 3ogv]
| β-galactosidase
| ''Hypocrea jecorina''
| 2-phenylethyl 1-thio-β-{{Smallcaps|d}}-galactopyranoside
| '''Glu200'''
| Glu298
| <cite>Maksimainen2011</cite>
|-
| [[GH36]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4fns 4fns]
| β-galactosidase
| ''Geobacillus stearothermophilus''
| 1-deoxy galactonojirimycin
| '''Asp584'''
| Asp478
| <cite>Merceron2012</cite>
|-
| [[GH37]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2jf4 2jf4]
| trehalase
| ''Escherichia coli''
| validoxylamine
| '''Asp312'''
| Glu496
| <cite>Gibson2007</cite>
|-
| [[GH38]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3czn 3czn]
| Golgi α-mannosidase II
| ''Drosophila melanogaster''
| GlcNAcMan(5)GlcNAc(2)
| '''Asp341'''
| Asp204
| <cite>Shah2008</cite>
|-
| [[GH39]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2bfg 2bfg]
| β-xylosidase
| ''Geobacillus stearothermophilus''
| 2,5-dinitrophenyl-β-{{Smallcaps|d}}-xyloside
| '''Glu160'''
| Glu278
| <cite>Czjzek2005</cite>
|-
| [[GH42]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ucf 4ucf]
| β-galactosidase
| ''Bifidobacterium bifidum''
| {{Smallcaps|d}}-galactose
| '''Glu161'''
| Glu320
| <cite>Godoy2016</cite>
|-
| [[GH43]]
| F
| 5-fold β-propeller
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3akh 3akh]
| exo-1,5-α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces avermitilis''
| α-1,5-arabinofuranotriose
| '''Glu196'''
| Asp220
| <cite>Fujimoto2010</cite>
|-
| [[GH44]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2eqd 2eqd]
| endoglucanase
| ''Clostridium thermocellum''
| cellooctaose
| '''Glu186'''
| Glu359
| <cite>Kitago2007</cite>
|-
| [[GH45]]
| none
| 6-stranded β-barrel
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4eng 4eng]
| endo-1,4-glucanase
| ''Humicola insolens''
| cellohexaose
| '''Asp121'''
| Asp10
| <cite>Davies1996</cite>
|-
| [[GH46]]
| I
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4olt 4olt]
| chitosanase
| ''Microbacterium sp.'' OU01
| hexa-glucosamine
| '''Glu25'''
| Asp43
| <cite>Lyu2014</cite>
|-
| [[GH47]]
| none
| (α/α)7
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1x9d 1x9d]
| α-mannosidase I
| ''Homo sapiens''
| Me-2-S-(α-Man)-2-thio-α-Man
| '''Asp463'''
| Glu599
| <cite>Karaveg2005</cite>, <cite>Nerinckx2008</cite>
|-
| [[GH48]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH8''
|
|
|
|
|
|
|-
| [[GH49]]
| N
| β-helix
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH28''
|
|
|
|
|
|
|-
| [[GH50]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4bq5 4bq5]
| exo-β-agarase
| ''Saccharophagus degradans''
| neoagarotetraose
| '''Glu535'''
| Glu695
| <cite>Pluvinage2013</cite>
|-
| [[GH51]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1qw9 1qw9]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Geobacillus stearothermophilus''
| PNP-{{Smallcaps|l}}-arabinofuranoside
| '''Glu175'''
| Glu294
| <cite>Hoevel2003</cite>
|-
| [[GH52]]
| O
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4c1p 4c1p]
| β-xylosidase
| ''Geobacillus thermoglucosidasius''
| xylobiose
| '''Asp517'''
| Glu537
| <cite>Espina2014</cite>
|-
| [[GH53]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2ccr 2ccr]
| β-1,4-galactanase
| ''Bacillus licheniformis''
| galactotriose
| '''Glu165'''
| Glu263
| <cite>Le_Nours2009</cite>
|-
| [[GH54]]
| none
| β-sandwich
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1wd4 1wd4]
| α-{{Smallcaps|l}}-arabinofuranosidase B
| ''Aspergillus kawachii''
| {{Smallcaps|l}}-arabinofuranose
| '''Asp297'''
| Glu221
| <cite>Miyanaga2004</cite>
|-
| [[GH55]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4tz5 4tz5]
| exo-β-1,3-glucanase
| ''Streptomyces sp.'' SirexAA-E
| laminarihexaose
| '''Glu502'''
| unknown
| <cite>Bianchetti2015</cite>
|-
| [[GH56]]
| none
| (β/α)7
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1fcv 1fcv]
| hyaluronidase
| ''Apis mellifera''
| (hyaluron.)4
| '''Glu113'''
| internal
| <cite>Markovic-Housley2000</cite>
|-
| [[GH57]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1k1y 1k1y]
| glucanotransferase
| ''Thermococcus litoralis''
| acarbose
| '''Asp214'''
| Glu123
| <cite>Imamura2003</cite>
|-
| [[GH59]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ccc 4ccc]
| β-galactocerebrosidase
| ''Mus musculus''
| PNP-β-{{Smallcaps|d}}-galactoside
| '''Glu182'''
| Glu258
| <cite>Hill2013</cite>
|-
| [[GH62]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3wn0 3wn0]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces coelicolor''
| β-{{Smallcaps|l}}-Arabinofuranose
| '''Glu361'''
| Asp202
| <cite>Maehara2014</cite>
|-
| [[GH63]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5ca3 5ca3]
| α-glucosidase
| ''Escherichia coli''
| glucose and lactose
| '''Asp501'''
| Glu727
| <cite>Miyazaki2016</cite>
|-
| [[GH65]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}4ktr 4ktr]
| 2-O-α-glucosylglycerol phosphorylase
| ''Bacillus selenitireducens''
| isofagomine
| '''Glu475'''
| phosphate
| <cite>Touhara2014</cite>
|-
| [[GH66]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5axh 5axh]
| dextranase
| ''Thermoanaerobacter pseudethanolicus''
| isomaltohexaose
| '''Glu374'''
| Asp312
| <cite>Suzuki2016</cite>
|-
| [[GH67]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1l8n 1l8n]
| α-glucuronidase
| ''Geobacillus stearothermophilus''
| 4-O-methyl-{{Smallcaps|d}}-glucuronic acid and xylotriose
| '''Glu286'''
| Asp364 Glu392
| <cite>Golan2004</cite>
|-
| [[GH68]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1pt2 1pt2]
| levansucrase
| ''Bacillus subtilis''
| sucrose
| '''Glu342'''
| Asp86
| <cite>Meng2003</cite>
|-
| [[GH70]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3aic 3aic]
| glucansucrase
| ''Streptococcus mutans''
| α-acarbose
| '''Glu515'''
| Asp477
| <cite>Ito2011</cite>
|-
| [[GH72]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w62 2w62]
| β-1,3-glucanotransferase
| ''Saccharomyces cerevisiae'' S288C
| laminaripentaose
| '''Glu176'''
| Glu275
| <cite>Hurtado-Gerrero2009</cite>
|-
| [[GH74]]
| none
| 7-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}2ebs 2ebs]
| cellobiohydrolase (OXG-RCBH)
| ''Geotrichum sp.'' m128
| xyloglucan heptasaccharide
| '''Asp465'''
| Asp35
| <cite>Yaoi2007</cite>
|-
| [[GH76]]
| none
| (α/α)6
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5agd 5agd]
| endo-α-1,6-mannanase
| ''Bacillus circulans''
| α-1,6-mannopentaose
| '''Asp125'''
| Asp124
| <cite>Thompson2015</cite>
|-
| [[GH77]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2oww 2oww]
| 4-α-glucanotransferase
| ''Thermus thermofilus''
| acarbose + 4-deoxy-α-{{Smallcaps|d}}-glucose
| '''Glu340'''
| Asp293
| <cite>Barends2007</cite>
|-
| [[GH78]]
| H
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3w5n 3w5n]
| α-{{Smallcaps|l}}-rhamnosidase
| ''Streptomyces avermitilis''
| {{Smallcaps|l}}-rhamnose
| '''Glu636'''
| Glu895
| <cite>Fujimoto2013</cite>
|-
| [[GH79]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5e9c 5e9c]
| heparanase
| ''Homo sapiens''
| heparin tetrasaccharide
| '''Glu225'''
| Glu343
| <cite>Wu2015</cite>
|-
| [[GH80]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH24''
|
|
|
|
|
|
|-
| [[GH81]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5t4g 5t4g]
| endo-β-1,3-glucanase
| ''Bacillus halodurans'' C-125
| laminarin
| '''Asp466'''
| Glu542
| <cite>Pluvinage2017</cite>
|-
| [[GH83]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH33''
|
|
|
|
|
|
|-
| [[GH84]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2chn 2chn]
| β-''N''-acetyl-glucosaminidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| NAG-thiazoline
| '''Glu242'''
| internal
| <cite>Dennis2006</cite>
|-
| [[GH85]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w92 2w92]
| endo-β-''N''-acetyl-glucosaminidase D
| ''Streptococcus pneumoniae'' TIGR4
| NAG-thiazoline
| '''Glu337'''
| internal
| <cite>Abbott2009</cite>
|-
| [[GH86]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4aw7 4aw7]
| β-porphyranase
| ''Bacteroides plebeius''
| porphyran fragment
| '''Glu152'''
| Glu279
| <cite>Hehemann_1_2012</cite>
|-
| [[GH89]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vcb 2vcb]
| α-''N''-acetyl-glucosaminidase
| ''Clostridium perfringens''
| PUGNAc
| '''Glu483'''
| Glu601
| <cite>Ficko-Blean2008</cite>
|-
| [[GH92]]
| none
| (α/α)6 and β-sandwich
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ww1 2ww1]
| α-1,2-mannosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| thiomannobioside
| '''Glu533'''
| Asp644 Asp642
| <cite>Zhu2009</cite>
|-
| [[GH93]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3a72 3a72]
| exo-arabinanase
| ''Penicillium chrysogenum''
| arabinobiose
| '''Glu246'''
| Glu174
| <cite>Sogabe2011</cite>
|-
| [[GH94]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4zli 4zli]
| cellobionic acid phosphorylase
| ''Saccharophagus degradans''
| 3-O-β-{{Smallcaps|d}}-glucopyranosyl-α-{{Smallcaps|d}}-glucopyranuronic acid
| '''Asp472'''
| phosphate
| <cite>Nam2015</cite>
|-
| [[GH95]]
| none
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ead 2ead]
| α-1,2-{{Smallcaps|l}}-fucosidase
| ''Bifidobacterium bifidum''
| Fuc-α-1,2-Gal
| '''Glu566'''
| Asn423 Asp766
| <cite>Nagae2007</cite>
|-
| [[GH97]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining + inverting
| '''''anti'''''
| [{{PDBlink}}2zq0 2zq0]
| α-glucosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| acarbose
| '''Glu532'''
| Glu508
| <cite>Kitamura2008</cite>
|-
| [[GH98]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2wmg 2wmg]
| endo-β-1,4-galactosidase
| ''Streptococcus pneumoniae''
| A-LewisY pentasaccharide
| '''Glu158'''
| Asp251 Glu301
| <cite>Higgins2009</cite>
|-
| [[GH99]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ad4 4ad4]
| endo-α-mannosidase
| ''Bacteroides xylanisolvens''
| glucose-1,3-isofagomine and α-1,2- mannobiose
| '''Glu336'''
| debated
| <cite>Thompson2012</cite>
|-
| [[GH100]]
| none
| (α/α)6 core
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5gop 5gop]
| invertase
| ''Anabaena (Nostoc) sp.'' pcc7120
| sucrose
| '''Asp188'''
| Glu414
| <cite>Xie2016</cite>
|-
| [[GH102]]
| none
| double-ψ β-barrel
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}2pi8 2pi8]
| lytic transglycosylase A
| ''Escherichia coli''
| chitohexaose
| '''Asp308'''
| none
| <cite>van_Straaten2007</cite>
|-
| [[GH103]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1d0k 1d0k]
| lytic transglycosylase SLT35
| ''Escherichia coli''
| murodipeptides
| '''Glu162'''
| internal
| <cite>van_Asselt2000</cite>
|-
| [[GH106]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5mwk 5mwk]
| α-{{Smallcaps|l}}-rhamnosidase BT_0986
| ''Bacteroides thetaiotaomicron''
| pectin heptasaccharide
| '''Glu461'''
| Glu593 or Glu561
| <cite>Ndeh2017</cite>
|-
| [[GH107]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| ''predicted syn by clan''
| ''see at GH29''
|
|
|
|
|
|
|-
| [[GH113]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4cd8 4cd8]
| β-mannanase
| ''Alicyclobacillus acidocaldarius''
| mannobioimidazole
| '''Glu151'''
| Glu231
| <cite>Williams2014</cite>
|-
| [[GH116]]
| O
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at GH52''
|
|
|
|
|
|
|-
| [[GH117]]
| none
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}4ak7 4ak7]
| α-1,3-3,6-anhydro-{{Smallcaps|l}}-galactosidase
| ''Bacteroides plebeius''
| neoagarobiose
| '''His302'''
| Asp90
| <cite>Hehemann_2_2012</cite>
|-
| [[GH120]]
| none
| parallel β-helix and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3vsv 3vsv]
| β-xylosidase XylC
| ''Thermoanaerobacterium saccharolyticum'' JW/SL-YS485
| {{Smallcaps|d}}-xylose
| '''Glu405'''
| Asp382
| <cite>Huang2012</cite>
|-
| [[GH123]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5fr0 5fr0]
| exo-β-N-acetyl-galactosaminidase
| ''Clostridium perfringens''
| ''N''-difluoroacetyl-{{Smallcaps|d}}-galactosamine
| '''Glu345'''
| internal
| <cite>Noach2016</cite>
|-
| [[GH125]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5m7y 5m7y]
| exo-α-1,6-mannosidase
| ''Clostridium perfringens''
| 1,6-α-mannotriose
| '''Asp220'''
| Glu393
| <cite>Alonso-Gil2016</cite>
|-
| [[GH127]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3wrg 3wrg]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bifidobacterium longum''
| {{Smallcaps|l}}-arabinose
| '''Glu322'''
| Cys417
| <cite>Huang2014</cite>
|-
| [[GH128]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH1''
|
|
|
|
|
|
|-
| [[GH130]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5b0s 5b0s]
| β-1,2-mannobiose phosphorylase
| ''Listeria innocua''
| β-1,2-mannotriose
| '''Asp141''' relay
| phosphate
| <cite>Tsuda2015</cite>
|-
| [[GH134]]
| none
| β + α
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5jug 5jug]
| β-mannanase
| ''Streptomyces sp.''
| mannopentaose
| '''Glu45'''
| Asp57
| <cite>Jin2016</cite>
|-
| [[GH136]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}5gqf 5gqf]
| lacto-N-biosidase
| ''Bifidobacterium longum''
| lacto-N-biose
| '''Asp411'''
| Asp418
| <cite>Yamada2017</cite>
|-
| [[GH137]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|l}}
| unknown
| '''''anti'''''
| [{{PDBlink}}5mui 5mui]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0996
| ''Bacteroides thetaiotaomicron''
| pectin oligosaccharide
| '''Glu240'''
| Glu159
| <cite>Ndeh2017</cite>

|-
| [[GH138]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}6hzg 6hzg]
| α-1,2-{{Smallcaps|d}}-galacturonidase
| ''Bacteroides paurosaccharolyticus''
| alpha-{{Smallcaps|d}}-galactopyranuronic
| '''Glu294'''
| Glu361
| <cite>Labourel2019</cite>
|-
| [[GH146]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5opj 5opj]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0349
| ''Bacteroides thetaiotaomicron''
| {{Smallcaps|l}}-arabinose
| '''Glu320'''
| Cys416
| <cite>Luis2018</cite>
|-
| [[GH147]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH148]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH149]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH157]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH158]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH161]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH162]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}6imw 5imw]
| endo-β-1,2-glucanase
| ''Talaromyces funiculosus''
| beta-1,2-glucan
| '''Glu262'''
| Asp446
| <cite>Tanaka2019</cite>
|-
| [http://www.cazy.org/GH0.html n.c.*]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2vjj 2vjj]
| endo-α-N-acetylglucosaminidase
| Bacteriophage HK620
| O18A1 O-antigen hexasaccharide
| '''Asp339'''
| Glu372
| <cite>Barbirz2008</cite>
|}
<nowiki>*</nowiki> n.c.: Found among the collection of [http://www.cazy.org/GH0.html non-classified GH sequences in the CAZy Database].

== References ==

<biblio>
# HeightmanVasella1999 Heightman TD and Vasella AT. ''Recent Insights into Inhibition, Structure, and Mechanism of Configuration-Retaining Glycosidases.'' Angew Chem Int Ed. 1999 38(6):750-770. [http://www3.interscience.wiley.com/journal/55000581/abstract Article online].
# Nerinckx2005 pmid=15642336
# Wu2012 pmid=23137336
# Perez1978 Pérez S and Marchessault RH. ''The exo-anomeric effect: experimental evidence from crystal structures.'' Carbohydr res. 1978 65:114-120. [http://dx.doi.org/10.1016/S0008-6215(00)84218-4 DOI:10.1016/S0008-6215(00)84218-4]
# Cramer1997 Cramer CJ, Truhlar DG, and French AD. ''Exo-anomeric effects on energies and geometries of different conformations of glucose and related systems in the gas phase and aqueous solution.'' Carbohydr res. 1997 298:1-14. [http://dx.doi.org/10.1016/S0008-6215(96)00297-2 DOI:10.1016/S0008-6215(96)00297-2]
# Johnson2009 pmid=19733839
# Alonso2016 pmid=26889578
# Gloster2006 pmid=17002288
# van_Bueren2009 pmid=18976664
# Hrmova2001 pmid=11709165
# Varrot2003 pmid=12595701
# Zhou1999 pmid=10508787
# Sulzenbacher1999 pmid=10200171
# Urbanikova2011 pmid=21501386
# Guerin2002 pmid=11884144
# Schubot2004 pmid=14756552
# Suzuki2009 pmid=19279191
# Wan2014 pmid=24419374
# Sandgren2004 pmid=15364577
# Uitdehaag1999 pmid=10331869
# Miyake2003 pmid=12741813
# Harris1993 pmid=8431441
# Allouch2004 pmid=15062085
# Wojtkowiak2013 pmid=23275163
# Papanikolau2001 pmid=11560481
# Prag2000 pmid=10884356
# Vocadlo2001 pmid=11518970
# Karlsen1996 pmid=15299731
# Baldwin1993 pmid=8259514
# Cartmell2008 pmid=18799462
# Fernandez-Leiro2010 pmid=20592022
# Abbott2007 pmid=17397864
# Sakurama2012 pmid=22451675
# Sim2008 pmid=18036614
# Verhaest2007 pmid=17335500
# Amaya2004 pmid=15130470
# Zhu2012 pmid=23015718
# Maksimainen2011 pmid=21130883
# Merceron2012 pmid=23012371
# Gibson2007 pmid=17455176
# Shah2008 pmid=18599462
# Czjzek2005 pmid=16212978
# Godoy2016 pmid=27685756
# Fujimoto2010 pmid=20739278
# Kitago2007 pmid=17905739
# Davies1996 pmid=15299721
# Lyu2014 pmid=24766439
# Karaveg2005 pmid=15713668
# Nerinckx2008 pmid=18619586
# Pluvinage2013 pmid=23921382
# Hoevel2003 pmid=14517232
# Espina2014 pmid=24816105
# Le_Nours2009 pmid=19089956
# Miyanaga2004 pmid=15292273
# Bianchetti2015 pmid=25752603
# Markovic-Housley2000 pmid=11080624
# Imamura2003 pmid=12618437
# Hill2013 pmid=24297913

# Maehara2014 pmid=24482228

# Miyazaki2016 pmid=27688023
# Touhara2014 pmid=24828502
# Suzuki2016 pmid=26494689
# Golan2004 pmid=14573597
# Meng2003 pmid=14517548
# Ito2011 pmid=21354427
# Hurtado-Gerrero2009 pmid=19097997
# Yaoi2007 pmid=17498741
# Thompson2015 pmid=25772148
# Barends2007 pmid=17420245
# Fujimoto2013 pmid=23486481
# Wu2015 pmid=26575439
# Pluvinage2017 pmid=28781080
# Dennis2006 pmid=16565725
# Abbott2009 pmid=19181667
# Hehemann_1_2012 pmid=23150581
# Ficko-Blean2008 pmid=18443291
# Zhu2009 pmid=20081828
# Sogabe2011 pmid=21543843
# Nam2015 pmid=26041776
# Nagae2007 pmid=17459873
# Kitamura2008 pmid=18981178
# Higgins2009 pmid=19608744
# van_Straaten2007 pmid=17502382
# van_Asselt2000 pmid=10684641
# Ndeh2017 pmid=28329766
# Labourel2019 pmid=30877196
# Luis2018 pmid=29255254
# Jin2016 Jin Y, Petricevic M, John A, Raich L, Jenkins H, Portela De Souza L, Cuskin F, Gilbert HJ, Rovira C, Goddard-Borger ED, Williams SJ, and Davies GJ. ''A β-Mannanase with a Lysozyme-like Fold and a Novel Molecular Catalytic Mechanism.'' ACS Cent Sci. 2016 Nov [http://dx.doi.org/10.1021/acscentsci.6b00232 DOI:10.1021/acscentsci.6b00232]
# Yamada2017 pmid=28392148
# Ohnuma2014 pmid=24582745
# Thompson2012 pmid=22219371
# Xie2016 pmid=27777307
# Williams2014 pmid=24339341
# Hehemann_2_2012 pmid=22393053
# Huang2012 pmid=22992047
# Noach2016 pmid=27038508
# Alonso-Gil2016 pmid=28026180
# Huang2014 Huang CH, Zhu Z, Cheng YS, Chan HC, Ko TP, Chen CC, Wang I, Ho MR, Hsu ST, Zeng YF, Huang YN, Liu JR, Guo RT. ''Structure and Catalytic Mechanism of a Glycoside Hydrolase Family-127 β-L-Arabinofuranosidase (HypBA1).'' J Bioprocess Biotech. 2014 4:171 [http://dx.doi.org/10.4172/2155-9821.1000171 DOI:10.4172/2155-9821.1000171]
# Tsuda2015 pmid=26632508
# Barbirz2008 pmid=18547389
# Tanaka2019 pmid=30926603

</biblio>

[[Category:Definitions and explanations]]

Syn/anti lateral protonation

2019-05-29T20:59:28Z

Wim Nerinckx:

{{CuratorApproved}}
* [[Author]]: ^^^Wim Nerinckx^^^
* [[Responsible Curator]]: ^^^Spencer Williams^^^

----

== Overview ==

This page provides a table that summarizes the spatial positioning of the catalytic [[general acid]] residue in the active sites of [[glycoside hydrolase]]s, relative to the substrate. The table below updates those found in the seminal paper on this concept by Heightman and Vasella <cite>HeightmanVasella1999</cite>, and a following paper by Nerinckx ''et al.'' <cite>Nerinckx2005</cite>.

== Background ==

The ''"not from above, but from the side"'' concept of semi-lateral glycosidic oxygen [[General_acid/base|protonation]] by [[glycoside hydrolase]]s was introduced by Heightman and Vasella <cite>HeightmanVasella1999</cite>. It was originally only described for [[Anomeric centre (alpha and beta)|beta]]-equatorial [[glycoside hydrolase]]s, but appears to be equally applicable to enzymes acting on an [[Anomeric centre (alpha and beta)|alpha]]-axial glycosidic bond <cite>Nerinckx2005</cite>. When dividing [[Sub-site nomenclature|subsite -1]] into half-spaces by a plane defined by the glycosidic oxygen and C1' and H1' of the –1 glycoside, many ligand-complexed structures reveal that the [[General_acid/base|proton donor]] is positioned either in the ''syn'' half-space (near the ring-oxygen of the –1 glycoside), or in the ''anti'' half-space (on the opposite side of the ring-oxygen). Members of the same GH [[Families|family]] appear to share a common ''syn'' or ''anti'' [[General_acid/base|protonator]] arrangement and further, this specificity appears to be preserved within [[Clans|Clans]] of [[Families|families]]. This page's compilation of [[Sub-site nomenclature|subsite -1]] occupied complexes shows that about 70% of all GH [[Families|families]] are ''anti'' [[General_acid/base|protonators]].

Closer inspection of crystal structures of [[Sub-site nomenclature|–1/+1 subsite]]-spanning substrates, or substrate-analogue ligands, in complex with enzymes reveals a further intriguing corollary <cite>Nerinckx2005 Wu2012</cite>. In substrate-bound complexes with ''anti'' [[General_acid/base|protonating]] GH enzymes, the scissile [[Anomeric centre (alpha and beta)|anomeric bond]] (often studied using the thio-analogue) shows a dihedral angle φ (O5'-C1'-[O,S]x-Cx) that is in the lowest-energy synclinal (gauche) conformation. The rationale for this is that a minus synclinal dihedral angle φ for an equatorial glycosidic bond, or plus synclinal for an axial glycosidic bond <cite>Perez1978</cite>, allows for hyperconjugative overlap of the C1'-O5' antibonding orbital with an antiperiplanar-oriented lone pair orbital lobe of the glycosidic oxygen, thereby creating partial double bond character and stabilization of the glycosidic bond by 4–5 kcal/mol; this ground-state stabilizing phenomenon is known as the ‘exo-anomeric effect’ <cite>Cramer1997 Johnson2009 Alonso2016</cite>. ''Anti'' [[General_acid/base|protonation]] occurs on the glycosidic oxygen’s antiperiplanar lone pair, thereby removing the stabilizing exo-anomeric effect. This suggests that ''anti'' [[General_acid/base|protonation]] is an enzymic approach for lowering the activation barrier leading to the [[Transition state|transition state]] (Figure 1 centre).

''Syn'' [[General_acid/base|protonating]] [[glycoside hydrolase]]s apparently make use of a different approach <cite>Nerinckx2005 Wu2012</cite>. In many [[Sub-site nomenclature|–1/+1 subsite]]-spanning ligand complexes, the dihedral angle φ of the scissile anomeric bond has been rotated away from its lowest-energy synclinal position: clockwise to minus-anticlinal or antiperiplanar for beta-equatorial; counterclockwise to plus-anticlinal or antiperiplanar for alpha-axial [[Anomeric centre (alpha and beta)|anomeric bonds]]. This removes the hyperconjugative overlap and thus also the stabilizing exo-anomeric effect. And because of this rotation, a lone pair of the glycosidic oxygen is directed into the ''syn'' half-space, allowing it to be protonated by the ''syn''-positioned [[General_acid/base|proton donor]] (Figure 1 right).

[[File:Syn_anti.jpg|800px|thumb|center|Figure 1. Newman projections, with the glycosidic oxygen as proximal atom and the anomeric carbon as distal atom, showing ''anti'' (centre) versus ''syn'' (right) semi-lateral [[General_acid/base|protonation]] in beta-equatorial (top) and alpha-axial (bottom) [[glycoside hydrolase]]s. The indicated φ is the dihedral angle for O5'-C1'-O4-C4.]]

== Table of ''syn/anti'' protonation examples ==

This table contains only one example per GH [[Families|family]] of a ligand-complexed protein structure where the ''syn'' or ''anti'' positioning of the [[General_acid/base|proton donor]] can be clearly observed; other examples may be available on a [[Families|family-by-family]] basis. The reader is thus advised to consult the [http://www.cazy.org/fam/acc_GH.html#table CAZy database] for a current, comprehensive list of CAZyme structures. Where available, the selected examples are Michaelis-type complexes with the ligand spanning the [[Sub-site nomenclature|-1/+1 subsites]], since these have an intact glycosidic or thioglycosidic bond, or are ''N''-analogs of the substrate (''e.g.'' acarbose). In some examples, the [[General_acid/base|proton donor]] has been mutated (''e.g.'', to the corresponding amide or to an alanine), and in those cases one may wish to look at a superposition of the given PDB example with the structure of the native enzyme. If a Michaelis-type complex is not yet available, the second and third example choices, respectively, are trapped glycosyl-enzyme [[intermediate]]s and product complexes where [[Sub-site nomenclature|subsite -1]] is occupied.

''Please also be aware that this is a large table with many data. Please contact the page Author or Responsible Curator with corrections.''

=== Table ===
This table can be re-sorted by clicking on the icons in the header (''javascript must be turned on in your browser''). To reset the page to be sorted by GH family, click the ''View'' tab at the very top of the page.

{| {{Prettytable}} class="sortable"
|- valign="top"
! '''Family'''
! '''Clan'''
! '''Structure fold '''
! '''Anomeric specificity'''
! '''Mechanism'''
! '''''Syn/anti'' protonator'''
! '''Example PDB ID'''
! '''Enzyme'''
! '''Organism'''
! '''Ligand'''
! '''General acid'''
! '''Nucleophile or General base'''
! '''Reference'''
|-
| [[GH1]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2cer 2cer]
| β-glycosidase S
| ''Sulfolobus solfataricus'' P2
| phenethyl glucoimidazole
| '''Glu206'''
| Glu387
| <cite>Gloster2006</cite>
|-
| [[GH2]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vzu 2vzu]
| exo-β-glucosaminidase
| ''Amicolatopsis orientalis''
| PNP-β-{{Smallcaps|d}}-glucosamine
| '''Glu469'''
| Glu541
| <cite>van_Bueren2009</cite>
|-
| [[GH3]]
| none
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1iex 1iex]
| exo-1,3-1,4-glucanase
| ''Hordeum vulgare''
| thiocellobiose
| '''Glu491'''
| Asp285
| <cite>Hrmova2001</cite>
|-
| [[GH5]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1h2j 1h2j]
| endo-β-1,4-glucanase
| ''Bacillus agaradhaerens''
| 2',4'-DNP-2-F-cellobioside
| '''Glu129'''
| Glu228
| <cite>Varrot2003</cite>
|-
| [[GH6]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1qjw 1qjw]
| cellobiohydrolase 2
| ''Hypocrea jecorina''
| (Glc)2-S-(Glc)2
| '''Asp221'''
| debated
| <cite>Zhou1999</cite>
|-
| [[GH7]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1ovw 1ovw]
| endo-1,4-glucanase
| ''Fusarium oxysporum''
| thio-(Glc)5
| '''Glu202'''
| Glu197
| <cite>Sulzenbacher1999</cite>
|-
| [[GH8]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1kwf 1kwf]
| endo-1,4-glucanase
| ''Clostridium thermocellum''
| cellopentaose
| '''Glu95'''
| Asp278
| <cite>Guerin2002</cite>
|-
| [[GH9]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1rq5 1rq5]
| cellobiohydrolase
| ''Clostridium thermocellum''
| cellotetraose
| '''Glu795'''
| Asp383
| <cite>Schubot2004</cite>
|-
| [[GH10]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2d24 2d24]
| β-1,4-xylanase
| ''Streptomyces olivaceoviridis'' E-86
| xylopentaose
| '''Glu128'''
| Glu236
| <cite>Suzuki2009</cite>
|-
| [[GH11]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}4hk8 4hk8]
| endo-β-1,4-xylanase
| ''Hypocrea jecorina''
| xylohexaose
| '''Glu177'''
| Glu86
| <cite>Wan2014</cite>
|-
| [[GH12]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1w2u 1w2u]
| endoglucanase
| ''Humicola grisea''
| thiocellotetraose
| '''Glu205'''
| Glu120
| <cite>Sandgren2004</cite>
|-
| [[GH13]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1cxk 1cxk]
| β-cyclodextrin glucanotransferase
| ''Bacillus circulans''
| maltononaose
| '''Glu257'''
| Asp229
| <cite>Uitdehaag1999</cite>
|-
| [[GH14]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1itc 1itc]
| β-amylase
| ''Bacillus cereus''
| maltopentaose
| '''Glu172'''
| Glu367
| <cite>Miyake2003</cite>
|-
| [[GH15]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1dog 1dog]
| glucoamylase
| ''Aspergillus awamori''
| 1-deoxynojirimycin
| '''Glu179'''
| Glu400
| <cite>Harris1993</cite>
|-
| [[GH16]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1urx 1urx]
| β-agarase A
| ''Zobellia galactanivorans''
| oligoagarose
| '''Glu152'''
| Glu147
| <cite>Allouch2004</cite>
|-
| [[GH17]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzj 4gzj]
| endo-β-1,3-glucanase
| ''Solanum tuberosum''
| laminaratriose + laminarabiose
| '''Glu118'''
| Glu259
| <cite>Wojtkowiak2013</cite>
|-
| [[GH18]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1ffr 1ffr]
| chitinase A
| ''Serratia marcescens''
| (NAG)6
| '''Glu315'''
| internal
| <cite>Papanikolau2001</cite>
|-
| [[GH19]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}3wh1 3wh1]
| chitinase
| ''Bryum coronatum''
| (GlcNAc)4
| '''Glu61'''
| Glu70
| <cite>Ohnuma2014</cite>
|-
| [[GH20]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1c7s 1c7s]
| chitobiase
| ''Serratia marcescens''
| chitobiose
| '''Glu540'''
| internal
| <cite>Prag2000</cite>
|-
| [[GH22]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1h6m 1h6m]
| lysozyme C
| ''Gallus gallus''
| Chit-2-F-chitosyl
| '''Glu35'''
| Asp52
| <cite>Vocadlo2001</cite>
|-
| [[GH23]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1lsp 1lsp]
| lysozyme G
| ''Cygnus atratus''
| Bulgecin A
| '''Glu73'''
| internal
| <cite>Karlsen1996</cite>
|-
| [[GH24]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}148l 148l]
| lysozyme E
| Bacteriophage T4
| chitobiosyl
| '''Glu11'''
| Glu26
| <cite>Baldwin1993</cite>
|-
| [[GH26]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vx6 2vx6]
| exo-β-mannanase
| ''Cellvibrio japonicus'' Ueda107
| Gal1Man4
| '''Glu221'''
| Glu338
| <cite>Cartmell2008</cite>
|-
| [[GH27]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}} / beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3lrm 3lrm]
| α-galactosidase
| ''Saccharomyces cerevisiae''
| raffinose
| '''Asp209'''
| Asp141
| <cite>Fernandez-Leiro2010</cite>
|-
| [[GH28]]
| N
| β-helix
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}2uvf 2uvf]
| exo-polygalacturonosidase
| ''Yersinia enterocolitica'' ATCC9610D
| digalacturonic acid
| '''Asp402'''
| Asp381 Asp403
| <cite>Abbott2007</cite>
|-
| [[GH29]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| '''''syn'''''
| [{{PDBlink}}3uet 3uet]
| α-1,3/4-fucosidase
| ''Bifidobacterium longum'' subsp. infantis
| lacto-''N''-fucopentaose II
| '''Glu217'''
| Asp172
| <cite>Sakurama2012</cite>
|-
| [[GH30]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2y24 2y24]
| glucurono-xylanase
| ''Dickea chrysanthemi'' D1
| glucuronoxylan tetrasaccharide
| '''Glu163'''
| Glu253
| <cite>Urbanikova2011</cite>
|-
| [[GH31]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2qmj 2qmj]
| maltase-glucoamylase
| ''Homo sapiens''
| acarbose
| '''Asp542'''
| Asp443
| <cite>Sim2008</cite>
|-
| [[GH32]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2add 2add]
| fructan β-(2,1)-fructosidase
| ''Cichorium intybus''
| sucrose
| '''Glu201'''
| Asp22
| <cite>Verhaest2007</cite>
|-
| [[GH33]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1s0i 1s0i]
| transsialidase
| ''Trypanosoma cruzi''
| sialyllactose
| '''Asp59'''
| Tyr342
| <cite>Amaya2004</cite>
|-
| [[GH34]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzw 4gzw]
| N2 neuraminidase
| ''Influenza'' A Tanzania/205/2010 H3N2
| α-{{Smallcaps|d}}-Neup5Ac-(2,3)-β-{{Smallcaps|d}}-Galp-(1,4)-β-{{Smallcaps|d}}-GlcpNAc
| '''Asp151'''
| Tyr406
| <cite>Zhu2012</cite>
|-
| [[GH35]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3ogv 3ogv]
| β-galactosidase
| ''Hypocrea jecorina''
| 2-phenylethyl 1-thio-β-{{Smallcaps|d}}-galactopyranoside
| '''Glu200'''
| Glu298
| <cite>Maksimainen2011</cite>
|-
| [[GH36]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4fns 4fns]
| β-galactosidase
| ''Geobacillus stearothermophilus''
| 1-deoxy galactonojirimycin
| '''Asp584'''
| Asp478
| <cite>Merceron2012</cite>
|-
| [[GH37]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2jf4 2jf4]
| trehalase
| ''Escherichia coli''
| validoxylamine
| '''Asp312'''
| Glu496
| <cite>Gibson2007</cite>
|-
| [[GH38]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3czn 3czn]
| Golgi α-mannosidase II
| ''Drosophila melanogaster''
| GlcNAcMan(5)GlcNAc(2)
| '''Asp341'''
| Asp204
| <cite>Shah2008</cite>
|-
| [[GH39]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2bfg 2bfg]
| β-xylosidase
| ''Geobacillus stearothermophilus''
| 2,5-dinitrophenyl-β-{{Smallcaps|d}}-xyloside
| '''Glu160'''
| Glu278
| <cite>Czjzek2005</cite>
|-
| [[GH42]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ucf 4ucf]
| β-galactosidase
| ''Bifidobacterium bifidum''
| {{Smallcaps|d}}-galactose
| '''Glu161'''
| Glu320
| <cite>Godoy2016</cite>
|-
| [[GH43]]
| F
| 5-fold β-propeller
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3akh 3akh]
| exo-1,5-α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces avermitilis''
| α-1,5-arabinofuranotriose
| '''Glu196'''
| Asp220
| <cite>Fujimoto2010</cite>
|-
| [[GH44]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2eqd 2eqd]
| endoglucanase
| ''Clostridium thermocellum''
| cellooctaose
| '''Glu186'''
| Glu359
| <cite>Kitago2007</cite>
|-
| [[GH45]]
| none
| 6-stranded β-barrel
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4eng 4eng]
| endo-1,4-glucanase
| ''Humicola insolens''
| cellohexaose
| '''Asp121'''
| Asp10
| <cite>Davies1996</cite>
|-
| [[GH46]]
| I
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4olt 4olt]
| chitosanase
| ''Microbacterium sp.'' OU01
| hexa-glucosamine
| '''Glu25'''
| Asp43
| <cite>Lyu2014</cite>
|-
| [[GH47]]
| none
| (α/α)7
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1x9d 1x9d]
| α-mannosidase I
| ''Homo sapiens''
| Me-2-S-(α-Man)-2-thio-α-Man
| '''Asp463'''
| Glu599
| <cite>Karaveg2005</cite>, <cite>Nerinckx2008</cite>
|-
| [[GH48]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH8''
|
|
|
|
|
|
|-
| [[GH49]]
| N
| β-helix
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH28''
|
|
|
|
|
|
|-
| [[GH50]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4bq5 4bq5]
| exo-β-agarase
| ''Saccharophagus degradans''
| neoagarotetraose
| '''Glu535'''
| Glu695
| <cite>Pluvinage2013</cite>
|-
| [[GH51]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1qw9 1qw9]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Geobacillus stearothermophilus''
| PNP-{{Smallcaps|l}}-arabinofuranoside
| '''Glu175'''
| Glu294
| <cite>Hoevel2003</cite>
|-
| [[GH52]]
| O
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4c1p 4c1p]
| β-xylosidase
| ''Geobacillus thermoglucosidasius''
| xylobiose
| '''Asp517'''
| Glu537
| <cite>Espina2014</cite>
|-
| [[GH53]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2ccr 2ccr]
| β-1,4-galactanase
| ''Bacillus licheniformis''
| galactotriose
| '''Glu165'''
| Glu263
| <cite>Le_Nours2009</cite>
|-
| [[GH54]]
| none
| β-sandwich
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1wd4 1wd4]
| α-{{Smallcaps|l}}-arabinofuranosidase B
| ''Aspergillus kawachii''
| {{Smallcaps|l}}-arabinofuranose
| '''Asp297'''
| Glu221
| <cite>Miyanaga2004</cite>
|-
| [[GH55]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4tz5 4tz5]
| exo-β-1,3-glucanase
| ''Streptomyces sp.'' SirexAA-E
| laminarihexaose
| '''Glu502'''
| unknown
| <cite>Bianchetti2015</cite>
|-
| [[GH56]]
| none
| (β/α)7
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1fcv 1fcv]
| hyaluronidase
| ''Apis mellifera''
| (hyaluron.)4
| '''Glu113'''
| internal
| <cite>Markovic-Housley2000</cite>
|-
| [[GH57]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1k1y 1k1y]
| glucanotransferase
| ''Thermococcus litoralis''
| acarbose
| '''Asp214'''
| Glu123
| <cite>Imamura2003</cite>
|-
| [[GH59]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ccc 4ccc]
| β-galactocerebrosidase
| ''Mus musculus''
| PNP-β-{{Smallcaps|d}}-galactoside
| '''Glu182'''
| Glu258
| <cite>Hill2013</cite>
|-
| [[GH62]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| ''predicted anti by clan''
| ''see at GH43''
|
|
|
|
|
| <cite>Maehara2014</cite>
|-
| [[GH63]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5ca3 5ca3]
| α-glucosidase
| ''Escherichia coli''
| glucose and lactose
| '''Asp501'''
| Glu727
| <cite>Miyazaki2016</cite>
|-
| [[GH65]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}4ktr 4ktr]
| 2-O-α-glucosylglycerol phosphorylase
| ''Bacillus selenitireducens''
| isofagomine
| '''Glu475'''
| phosphate
| <cite>Touhara2014</cite>
|-
| [[GH66]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5axh 5axh]
| dextranase
| ''Thermoanaerobacter pseudethanolicus''
| isomaltohexaose
| '''Glu374'''
| Asp312
| <cite>Suzuki2016</cite>
|-
| [[GH67]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1l8n 1l8n]
| α-glucuronidase
| ''Geobacillus stearothermophilus''
| 4-O-methyl-{{Smallcaps|d}}-glucuronic acid and xylotriose
| '''Glu286'''
| Asp364 Glu392
| <cite>Golan2004</cite>
|-
| [[GH68]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1pt2 1pt2]
| levansucrase
| ''Bacillus subtilis''
| sucrose
| '''Glu342'''
| Asp86
| <cite>Meng2003</cite>
|-
| [[GH70]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3aic 3aic]
| glucansucrase
| ''Streptococcus mutans''
| α-acarbose
| '''Glu515'''
| Asp477
| <cite>Ito2011</cite>
|-
| [[GH72]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w62 2w62]
| β-1,3-glucanotransferase
| ''Saccharomyces cerevisiae'' S288C
| laminaripentaose
| '''Glu176'''
| Glu275
| <cite>Hurtado-Gerrero2009</cite>
|-
| [[GH74]]
| none
| 7-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}2ebs 2ebs]
| cellobiohydrolase (OXG-RCBH)
| ''Geotrichum sp.'' m128
| xyloglucan heptasaccharide
| '''Asp465'''
| Asp35
| <cite>Yaoi2007</cite>
|-
| [[GH76]]
| none
| (α/α)6
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5agd 5agd]
| endo-α-1,6-mannanase
| ''Bacillus circulans''
| α-1,6-mannopentaose
| '''Asp125'''
| Asp124
| <cite>Thompson2015</cite>
|-
| [[GH77]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2oww 2oww]
| 4-α-glucanotransferase
| ''Thermus thermofilus''
| acarbose + 4-deoxy-α-{{Smallcaps|d}}-glucose
| '''Glu340'''
| Asp293
| <cite>Barends2007</cite>
|-
| [[GH78]]
| H
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3w5n 3w5n]
| α-{{Smallcaps|l}}-rhamnosidase
| ''Streptomyces avermitilis''
| {{Smallcaps|l}}-rhamnose
| '''Glu636'''
| Glu895
| <cite>Fujimoto2013</cite>
|-
| [[GH79]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5e9c 5e9c]
| heparanase
| ''Homo sapiens''
| heparin tetrasaccharide
| '''Glu225'''
| Glu343
| <cite>Wu2015</cite>
|-
| [[GH80]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH24''
|
|
|
|
|
|
|-
| [[GH81]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5t4g 5t4g]
| endo-β-1,3-glucanase
| ''Bacillus halodurans'' C-125
| laminarin
| '''Asp466'''
| Glu542
| <cite>Pluvinage2017</cite>
|-
| [[GH83]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH33''
|
|
|
|
|
|
|-
| [[GH84]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2chn 2chn]
| β-''N''-acetyl-glucosaminidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| NAG-thiazoline
| '''Glu242'''
| internal
| <cite>Dennis2006</cite>
|-
| [[GH85]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w92 2w92]
| endo-β-''N''-acetyl-glucosaminidase D
| ''Streptococcus pneumoniae'' TIGR4
| NAG-thiazoline
| '''Glu337'''
| internal
| <cite>Abbott2009</cite>
|-
| [[GH86]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4aw7 4aw7]
| β-porphyranase
| ''Bacteroides plebeius''
| porphyran fragment
| '''Glu152'''
| Glu279
| <cite>Hehemann_1_2012</cite>
|-
| [[GH89]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vcb 2vcb]
| α-''N''-acetyl-glucosaminidase
| ''Clostridium perfringens''
| PUGNAc
| '''Glu483'''
| Glu601
| <cite>Ficko-Blean2008</cite>
|-
| [[GH92]]
| none
| (α/α)6 and β-sandwich
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ww1 2ww1]
| α-1,2-mannosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| thiomannobioside
| '''Glu533'''
| Asp644 Asp642
| <cite>Zhu2009</cite>
|-
| [[GH93]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3a72 3a72]
| exo-arabinanase
| ''Penicillium chrysogenum''
| arabinobiose
| '''Glu246'''
| Glu174
| <cite>Sogabe2011</cite>
|-
| [[GH94]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4zli 4zli]
| cellobionic acid phosphorylase
| ''Saccharophagus degradans''
| 3-O-β-{{Smallcaps|d}}-glucopyranosyl-α-{{Smallcaps|d}}-glucopyranuronic acid
| '''Asp472'''
| phosphate
| <cite>Nam2015</cite>
|-
| [[GH95]]
| none
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ead 2ead]
| α-1,2-{{Smallcaps|l}}-fucosidase
| ''Bifidobacterium bifidum''
| Fuc-α-1,2-Gal
| '''Glu566'''
| Asn423 Asp766
| <cite>Nagae2007</cite>
|-
| [[GH97]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining + inverting
| '''''anti'''''
| [{{PDBlink}}2zq0 2zq0]
| α-glucosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| acarbose
| '''Glu532'''
| Glu508
| <cite>Kitamura2008</cite>
|-
| [[GH98]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2wmg 2wmg]
| endo-β-1,4-galactosidase
| ''Streptococcus pneumoniae''
| A-LewisY pentasaccharide
| '''Glu158'''
| Asp251 Glu301
| <cite>Higgins2009</cite>
|-
| [[GH99]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ad4 4ad4]
| endo-α-mannosidase
| ''Bacteroides xylanisolvens''
| glucose-1,3-isofagomine and α-1,2- mannobiose
| '''Glu336'''
| debated
| <cite>Thompson2012</cite>
|-
| [[GH100]]
| none
| (α/α)6 core
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5gop 5gop]
| invertase
| ''Anabaena (Nostoc) sp.'' pcc7120
| sucrose
| '''Asp188'''
| Glu414
| <cite>Xie2016</cite>
|-
| [[GH102]]
| none
| double-ψ β-barrel
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}2pi8 2pi8]
| lytic transglycosylase A
| ''Escherichia coli''
| chitohexaose
| '''Asp308'''
| none
| <cite>van_Straaten2007</cite>
|-
| [[GH103]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1d0k 1d0k]
| lytic transglycosylase SLT35
| ''Escherichia coli''
| murodipeptides
| '''Glu162'''
| internal
| <cite>van_Asselt2000</cite>
|-
| [[GH106]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5mwk 5mwk]
| α-{{Smallcaps|l}}-rhamnosidase BT_0986
| ''Bacteroides thetaiotaomicron''
| pectin heptasaccharide
| '''Glu461'''
| Glu593 or Glu561
| <cite>Ndeh2017</cite>
|-
| [[GH107]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| ''predicted syn by clan''
| ''see at GH29''
|
|
|
|
|
|
|-
| [[GH113]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4cd8 4cd8]
| β-mannanase
| ''Alicyclobacillus acidocaldarius''
| mannobioimidazole
| '''Glu151'''
| Glu231
| <cite>Williams2014</cite>
|-
| [[GH116]]
| O
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at GH52''
|
|
|
|
|
|
|-
| [[GH117]]
| none
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}4ak7 4ak7]
| α-1,3-3,6-anhydro-{{Smallcaps|l}}-galactosidase
| ''Bacteroides plebeius''
| neoagarobiose
| '''His302'''
| Asp90
| <cite>Hehemann_2_2012</cite>
|-
| [[GH120]]
| none
| parallel β-helix and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3vsv 3vsv]
| β-xylosidase XylC
| ''Thermoanaerobacterium saccharolyticum'' JW/SL-YS485
| {{Smallcaps|d}}-xylose
| '''Glu405'''
| Asp382
| <cite>Huang2012</cite>
|-
| [[GH123]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5fr0 5fr0]
| exo-β-N-acetyl-galactosaminidase
| ''Clostridium perfringens''
| ''N''-difluoroacetyl-{{Smallcaps|d}}-galactosamine
| '''Glu345'''
| internal
| <cite>Noach2016</cite>
|-
| [[GH125]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5m7y 5m7y]
| exo-α-1,6-mannosidase
| ''Clostridium perfringens''
| 1,6-α-mannotriose
| '''Asp220'''
| Glu393
| <cite>Alonso-Gil2016</cite>
|-
| [[GH127]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3wrg 3wrg]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bifidobacterium longum''
| {{Smallcaps|l}}-arabinose
| '''Glu322'''
| Cys417
| <cite>Huang2014</cite>
|-
| [[GH128]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH1''
|
|
|
|
|
|
|-
| [[GH130]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5b0s 5b0s]
| β-1,2-mannobiose phosphorylase
| ''Listeria innocua''
| β-1,2-mannotriose
| '''Asp141''' relay
| phosphate
| <cite>Tsuda2015</cite>
|-
| [[GH134]]
| none
| β + α
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5jug 5jug]
| β-mannanase
| ''Streptomyces sp.''
| mannopentaose
| '''Glu45'''
| Asp57
| <cite>Jin2016</cite>
|-
| [[GH136]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}5gqf 5gqf]
| lacto-N-biosidase
| ''Bifidobacterium longum''
| lacto-N-biose
| '''Asp411'''
| Asp418
| <cite>Yamada2017</cite>
|-
| [[GH137]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|l}}
| unknown
| '''''anti'''''
| [{{PDBlink}}5mui 5mui]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0996
| ''Bacteroides thetaiotaomicron''
| pectin oligosaccharide
| '''Glu240'''
| Glu159
| <cite>Ndeh2017</cite>

|-
| [[GH138]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}6hzg 6hzg]
| α-1,2-{{Smallcaps|d}}-galacturonidase
| ''Bacteroides paurosaccharolyticus''
| alpha-{{Smallcaps|d}}-galactopyranuronic
| '''Glu294'''
| Glu361
| <cite>Labourel2019</cite>
|-
| [[GH146]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5opj 5opj]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0349
| ''Bacteroides thetaiotaomicron''
| {{Smallcaps|l}}-arabinose
| '''Glu320'''
| Cys416
| <cite>Luis2018</cite>
|-
| [[GH147]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH148]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH149]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH157]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH158]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH161]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH162]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}6imw 5imw]
| endo-β-1,2-glucanase
| ''Talaromyces funiculosus''
| beta-1,2-glucan
| '''Glu262'''
| Asp446
| <cite>Tanaka2019</cite>
|-
| [http://www.cazy.org/GH0.html n.c.*]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2vjj 2vjj]
| endo-α-N-acetylglucosaminidase
| Bacteriophage HK620
| O18A1 O-antigen hexasaccharide
| '''Asp339'''
| Glu372
| <cite>Barbirz2008</cite>
|}
<nowiki>*</nowiki> n.c.: Found among the collection of [http://www.cazy.org/GH0.html non-classified GH sequences in the CAZy Database].

== References ==

<biblio>
# HeightmanVasella1999 Heightman TD and Vasella AT. ''Recent Insights into Inhibition, Structure, and Mechanism of Configuration-Retaining Glycosidases.'' Angew Chem Int Ed. 1999 38(6):750-770. [http://www3.interscience.wiley.com/journal/55000581/abstract Article online].
# Nerinckx2005 pmid=15642336
# Wu2012 pmid=23137336
# Perez1978 Pérez S and Marchessault RH. ''The exo-anomeric effect: experimental evidence from crystal structures.'' Carbohydr res. 1978 65:114-120. [http://dx.doi.org/10.1016/S0008-6215(00)84218-4 DOI:10.1016/S0008-6215(00)84218-4]
# Cramer1997 Cramer CJ, Truhlar DG, and French AD. ''Exo-anomeric effects on energies and geometries of different conformations of glucose and related systems in the gas phase and aqueous solution.'' Carbohydr res. 1997 298:1-14. [http://dx.doi.org/10.1016/S0008-6215(96)00297-2 DOI:10.1016/S0008-6215(96)00297-2]
# Johnson2009 pmid=19733839
# Alonso2016 pmid=26889578
# Gloster2006 pmid=17002288
# van_Bueren2009 pmid=18976664
# Hrmova2001 pmid=11709165
# Varrot2003 pmid=12595701
# Zhou1999 pmid=10508787
# Sulzenbacher1999 pmid=10200171
# Urbanikova2011 pmid=21501386
# Guerin2002 pmid=11884144
# Schubot2004 pmid=14756552
# Suzuki2009 pmid=19279191
# Wan2014 pmid=24419374
# Sandgren2004 pmid=15364577
# Uitdehaag1999 pmid=10331869
# Miyake2003 pmid=12741813
# Harris1993 pmid=8431441
# Allouch2004 pmid=15062085

# Wojtkowiak2013 pmid=23275163
# Papanikolau2001 pmid=11560481

# Prag2000 pmid=10884356
# Vocadlo2001 pmid=11518970
# Karlsen1996 pmid=15299731
# Baldwin1993 pmid=8259514
# Cartmell2008 pmid=18799462
# Fernandez-Leiro2010 pmid=20592022
# Abbott2007 pmid=17397864
# Sakurama2012 pmid=22451675
# Sim2008 pmid=18036614
# Verhaest2007 pmid=17335500
# Amaya2004 pmid=15130470
# Zhu2012 pmid=23015718
# Maksimainen2011 pmid=21130883
# Merceron2012 pmid=23012371
# Gibson2007 pmid=17455176
# Shah2008 pmid=18599462
# Czjzek2005 pmid=16212978
# Godoy2016 pmid=27685756
# Fujimoto2010 pmid=20739278
# Kitago2007 pmid=17905739
# Davies1996 pmid=15299721
# Lyu2014 pmid=24766439
# Karaveg2005 pmid=15713668
# Nerinckx2008 pmid=18619586
# Pluvinage2013 pmid=23921382
# Hoevel2003 pmid=14517232
# Espina2014 pmid=24816105
# Le_Nours2009 pmid=19089956
# Miyanaga2004 pmid=15292273
# Bianchetti2015 pmid=25752603
# Markovic-Housley2000 pmid=11080624
# Imamura2003 pmid=12618437
# Hill2013 pmid=24297913
# Miyazaki2016 pmid=27688023
# Touhara2014 pmid=24828502
# Suzuki2016 pmid=26494689
# Golan2004 pmid=14573597
# Meng2003 pmid=14517548
# Ito2011 pmid=21354427
# Hurtado-Gerrero2009 pmid=19097997
# Yaoi2007 pmid=17498741
# Thompson2015 pmid=25772148
# Barends2007 pmid=17420245
# Fujimoto2013 pmid=23486481
# Wu2015 pmid=26575439
# Pluvinage2017 pmid=28781080
# Dennis2006 pmid=16565725
# Abbott2009 pmid=19181667
# Hehemann_1_2012 pmid=23150581
# Ficko-Blean2008 pmid=18443291
# Zhu2009 pmid=20081828
# Sogabe2011 pmid=21543843
# Nam2015 pmid=26041776
# Nagae2007 pmid=17459873
# Kitamura2008 pmid=18981178
# Higgins2009 pmid=19608744
# van_Straaten2007 pmid=17502382
# van_Asselt2000 pmid=10684641
# Ndeh2017 pmid=28329766
# Labourel2019 pmid=30877196

# Luis2018 pmid=29255254
# Jin2016 Jin Y, Petricevic M, John A, Raich L, Jenkins H, Portela De Souza L, Cuskin F, Gilbert HJ, Rovira C, Goddard-Borger ED, Williams SJ, and Davies GJ. ''A β-Mannanase with a Lysozyme-like Fold and a Novel Molecular Catalytic Mechanism.'' ACS Cent Sci. 2016 Nov [http://dx.doi.org/10.1021/acscentsci.6b00232 DOI:10.1021/acscentsci.6b00232]
# Yamada2017 pmid=28392148
# Ohnuma2014 pmid=24582745
# Thompson2012 pmid=22219371
# Xie2016 pmid=27777307
# Williams2014 pmid=24339341
# Hehemann_2_2012 pmid=22393053
# Huang2012 pmid=22992047
# Noach2016 pmid=27038508
# Alonso-Gil2016 pmid=28026180
# Huang2014 Huang CH, Zhu Z, Cheng YS, Chan HC, Ko TP, Chen CC, Wang I, Ho MR, Hsu ST, Zeng YF, Huang YN, Liu JR, Guo RT. ''Structure and Catalytic Mechanism of a Glycoside Hydrolase Family-127 β-L-Arabinofuranosidase (HypBA1).'' J Bioprocess Biotech. 2014 4:171 [http://dx.doi.org/10.4172/2155-9821.1000171 DOI:10.4172/2155-9821.1000171]
# Tsuda2015 pmid=26632508
# Barbirz2008 pmid=18547389
# Tanaka2019 pmid=30926603

</biblio>

[[Category:Definitions and explanations]]

Syn/anti lateral protonation

2019-05-29T20:55:52Z

Wim Nerinckx: GH17 is anti

{{CuratorApproved}}
* [[Author]]: ^^^Wim Nerinckx^^^
* [[Responsible Curator]]: ^^^Spencer Williams^^^

----

== Overview ==

This page provides a table that summarizes the spatial positioning of the catalytic [[general acid]] residue in the active sites of [[glycoside hydrolase]]s, relative to the substrate. The table below updates those found in the seminal paper on this concept by Heightman and Vasella <cite>HeightmanVasella1999</cite>, and a following paper by Nerinckx ''et al.'' <cite>Nerinckx2005</cite>.

== Background ==

The ''"not from above, but from the side"'' concept of semi-lateral glycosidic oxygen [[General_acid/base|protonation]] by [[glycoside hydrolase]]s was introduced by Heightman and Vasella <cite>HeightmanVasella1999</cite>. It was originally only described for [[Anomeric centre (alpha and beta)|beta]]-equatorial [[glycoside hydrolase]]s, but appears to be equally applicable to enzymes acting on an [[Anomeric centre (alpha and beta)|alpha]]-axial glycosidic bond <cite>Nerinckx2005</cite>. When dividing [[Sub-site nomenclature|subsite -1]] into half-spaces by a plane defined by the glycosidic oxygen and C1' and H1' of the –1 glycoside, many ligand-complexed structures reveal that the [[General_acid/base|proton donor]] is positioned either in the ''syn'' half-space (near the ring-oxygen of the –1 glycoside), or in the ''anti'' half-space (on the opposite side of the ring-oxygen). Members of the same GH [[Families|family]] appear to share a common ''syn'' or ''anti'' [[General_acid/base|protonator]] arrangement and further, this specificity appears to be preserved within [[Clans|Clans]] of [[Families|families]]. This page's compilation of [[Sub-site nomenclature|subsite -1]] occupied complexes shows that about 70% of all GH [[Families|families]] are ''anti'' [[General_acid/base|protonators]].

Closer inspection of crystal structures of [[Sub-site nomenclature|–1/+1 subsite]]-spanning substrates, or substrate-analogue ligands, in complex with enzymes reveals a further intriguing corollary <cite>Nerinckx2005 Wu2012</cite>. In substrate-bound complexes with ''anti'' [[General_acid/base|protonating]] GH enzymes, the scissile [[Anomeric centre (alpha and beta)|anomeric bond]] (often studied using the thio-analogue) shows a dihedral angle φ (O5'-C1'-[O,S]x-Cx) that is in the lowest-energy synclinal (gauche) conformation. The rationale for this is that a minus synclinal dihedral angle φ for an equatorial glycosidic bond, or plus synclinal for an axial glycosidic bond <cite>Perez1978</cite>, allows for hyperconjugative overlap of the C1'-O5' antibonding orbital with an antiperiplanar-oriented lone pair orbital lobe of the glycosidic oxygen, thereby creating partial double bond character and stabilization of the glycosidic bond by 4–5 kcal/mol; this ground-state stabilizing phenomenon is known as the ‘exo-anomeric effect’ <cite>Cramer1997 Johnson2009 Alonso2016</cite>. ''Anti'' [[General_acid/base|protonation]] occurs on the glycosidic oxygen’s antiperiplanar lone pair, thereby removing the stabilizing exo-anomeric effect. This suggests that ''anti'' [[General_acid/base|protonation]] is an enzymic approach for lowering the activation barrier leading to the [[Transition state|transition state]] (Figure 1 centre).

''Syn'' [[General_acid/base|protonating]] [[glycoside hydrolase]]s apparently make use of a different approach <cite>Nerinckx2005 Wu2012</cite>. In many [[Sub-site nomenclature|–1/+1 subsite]]-spanning ligand complexes, the dihedral angle φ of the scissile anomeric bond has been rotated away from its lowest-energy synclinal position: clockwise to minus-anticlinal or antiperiplanar for beta-equatorial; counterclockwise to plus-anticlinal or antiperiplanar for alpha-axial [[Anomeric centre (alpha and beta)|anomeric bonds]]. This removes the hyperconjugative overlap and thus also the stabilizing exo-anomeric effect. And because of this rotation, a lone pair of the glycosidic oxygen is directed into the ''syn'' half-space, allowing it to be protonated by the ''syn''-positioned [[General_acid/base|proton donor]] (Figure 1 right).

[[File:Syn_anti.jpg|800px|thumb|center|Figure 1. Newman projections, with the glycosidic oxygen as proximal atom and the anomeric carbon as distal atom, showing ''anti'' (centre) versus ''syn'' (right) semi-lateral [[General_acid/base|protonation]] in beta-equatorial (top) and alpha-axial (bottom) [[glycoside hydrolase]]s. The indicated φ is the dihedral angle for O5'-C1'-O4-C4.]]

== Table of ''syn/anti'' protonation examples ==

This table contains only one example per GH [[Families|family]] of a ligand-complexed protein structure where the ''syn'' or ''anti'' positioning of the [[General_acid/base|proton donor]] can be clearly observed; other examples may be available on a [[Families|family-by-family]] basis. The reader is thus advised to consult the [http://www.cazy.org/fam/acc_GH.html#table CAZy database] for a current, comprehensive list of CAZyme structures. Where available, the selected examples are Michaelis-type complexes with the ligand spanning the [[Sub-site nomenclature|-1/+1 subsites]], since these have an intact glycosidic or thioglycosidic bond, or are ''N''-analogs of the substrate (''e.g.'' acarbose). In some examples, the [[General_acid/base|proton donor]] has been mutated (''e.g.'', to the corresponding amide or to an alanine), and in those cases one may wish to look at a superposition of the given PDB example with the structure of the native enzyme. If a Michaelis-type complex is not yet available, the second and third example choices, respectively, are trapped glycosyl-enzyme [[intermediate]]s and product complexes where [[Sub-site nomenclature|subsite -1]] is occupied.

''Please also be aware that this is a large table with many data. Please contact the page Author or Responsible Curator with corrections.''

=== Table ===
This table can be re-sorted by clicking on the icons in the header (''javascript must be turned on in your browser''). To reset the page to be sorted by GH family, click the ''View'' tab at the very top of the page.

{| {{Prettytable}} class="sortable"
|- valign="top"
! '''Family'''
! '''Clan'''
! '''Structure fold '''
! '''Anomeric specificity'''
! '''Mechanism'''
! '''''Syn/anti'' protonator'''
! '''Example PDB ID'''
! '''Enzyme'''
! '''Organism'''
! '''Ligand'''
! '''General acid'''
! '''Nucleophile or General base'''
! '''Reference'''
|-
| [[GH1]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2cer 2cer]
| β-glycosidase S
| ''Sulfolobus solfataricus'' P2
| phenethyl glucoimidazole
| '''Glu206'''
| Glu387
| <cite>Gloster2006</cite>
|-
| [[GH2]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vzu 2vzu]
| exo-β-glucosaminidase
| ''Amicolatopsis orientalis''
| PNP-β-{{Smallcaps|d}}-glucosamine
| '''Glu469'''
| Glu541
| <cite>van_Bueren2009</cite>
|-
| [[GH3]]
| none
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1iex 1iex]
| exo-1,3-1,4-glucanase
| ''Hordeum vulgare''
| thiocellobiose
| '''Glu491'''
| Asp285
| <cite>Hrmova2001</cite>
|-
| [[GH5]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1h2j 1h2j]
| endo-β-1,4-glucanase
| ''Bacillus agaradhaerens''
| 2',4'-DNP-2-F-cellobioside
| '''Glu129'''
| Glu228
| <cite>Varrot2003</cite>
|-
| [[GH6]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1qjw 1qjw]
| cellobiohydrolase 2
| ''Hypocrea jecorina''
| (Glc)2-S-(Glc)2
| '''Asp221'''
| debated
| <cite>Zhou1999</cite>
|-
| [[GH7]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1ovw 1ovw]
| endo-1,4-glucanase
| ''Fusarium oxysporum''
| thio-(Glc)5
| '''Glu202'''
| Glu197
| <cite>Sulzenbacher1999</cite>
|-
| [[GH8]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1kwf 1kwf]
| endo-1,4-glucanase
| ''Clostridium thermocellum''
| cellopentaose
| '''Glu95'''
| Asp278
| <cite>Guerin2002</cite>
|-
| [[GH9]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1rq5 1rq5]
| cellobiohydrolase
| ''Clostridium thermocellum''
| cellotetraose
| '''Glu795'''
| Asp383
| <cite>Schubot2004</cite>
|-
| [[GH10]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2d24 2d24]
| β-1,4-xylanase
| ''Streptomyces olivaceoviridis'' E-86
| xylopentaose
| '''Glu128'''
| Glu236
| <cite>Suzuki2009</cite>
|-
| [[GH11]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}4hk8 4hk8]
| endo-β-1,4-xylanase
| ''Hypocrea jecorina''
| xylohexaose
| '''Glu177'''
| Glu86
| <cite>Wan2014</cite>
|-
| [[GH12]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1w2u 1w2u]
| endoglucanase
| ''Humicola grisea''
| thiocellotetraose
| '''Glu205'''
| Glu120
| <cite>Sandgren2004</cite>
|-
| [[GH13]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1cxk 1cxk]
| β-cyclodextrin glucanotransferase
| ''Bacillus circulans''
| maltononaose
| '''Glu257'''
| Asp229
| <cite>Uitdehaag1999</cite>
|-
| [[GH14]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1itc 1itc]
| β-amylase
| ''Bacillus cereus''
| maltopentaose
| '''Glu172'''
| Glu367
| <cite>Miyake2003</cite>
|-
| [[GH15]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1dog 1dog]
| glucoamylase
| ''Aspergillus awamori''
| 1-deoxynojirimycin
| '''Glu179'''
| Glu400
| <cite>Harris1993</cite>
|-
| [[GH16]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1urx 1urx]
| β-agarase A
| ''Zobellia galactanivorans''
| oligoagarose
| '''Glu152'''
| Glu147
| <cite>Allouch2004</cite>
|-
| [[GH17]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3wn0 3wn0]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Solanum tuberosum''
| laminaratriose + laminarabiose
| '''Glu118'''
| Glu259
| <cite>Wojtkowiak2013</cite>
|-
| [[GH18]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1ffr 1ffr]
| chitinase A
| ''Serratia marcescens''
| (NAG)6
| '''Glu315'''
| internal
| <cite>Papanikolau2001</cite>
|-
| [[GH19]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}3wh1 3wh1]
| chitinase
| ''Bryum coronatum''
| (GlcNAc)4
| '''Glu61'''
| Glu70
| <cite>Ohnuma2014</cite>
|-
| [[GH20]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1c7s 1c7s]
| chitobiase
| ''Serratia marcescens''
| chitobiose
| '''Glu540'''
| internal
| <cite>Prag2000</cite>
|-
| [[GH22]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1h6m 1h6m]
| lysozyme C
| ''Gallus gallus''
| Chit-2-F-chitosyl
| '''Glu35'''
| Asp52
| <cite>Vocadlo2001</cite>
|-
| [[GH23]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1lsp 1lsp]
| lysozyme G
| ''Cygnus atratus''
| Bulgecin A
| '''Glu73'''
| internal
| <cite>Karlsen1996</cite>
|-
| [[GH24]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}148l 148l]
| lysozyme E
| Bacteriophage T4
| chitobiosyl
| '''Glu11'''
| Glu26
| <cite>Baldwin1993</cite>
|-
| [[GH26]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vx6 2vx6]
| exo-β-mannanase
| ''Cellvibrio japonicus'' Ueda107
| Gal1Man4
| '''Glu221'''
| Glu338
| <cite>Cartmell2008</cite>
|-
| [[GH27]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}} / beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3lrm 3lrm]
| α-galactosidase
| ''Saccharomyces cerevisiae''
| raffinose
| '''Asp209'''
| Asp141
| <cite>Fernandez-Leiro2010</cite>
|-
| [[GH28]]
| N
| β-helix
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}2uvf 2uvf]
| exo-polygalacturonosidase
| ''Yersinia enterocolitica'' ATCC9610D
| digalacturonic acid
| '''Asp402'''
| Asp381 Asp403
| <cite>Abbott2007</cite>
|-
| [[GH29]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| '''''syn'''''
| [{{PDBlink}}3uet 3uet]
| α-1,3/4-fucosidase
| ''Bifidobacterium longum'' subsp. infantis
| lacto-''N''-fucopentaose II
| '''Glu217'''
| Asp172
| <cite>Sakurama2012</cite>
|-
| [[GH30]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2y24 2y24]
| glucurono-xylanase
| ''Dickea chrysanthemi'' D1
| glucuronoxylan tetrasaccharide
| '''Glu163'''
| Glu253
| <cite>Urbanikova2011</cite>
|-
| [[GH31]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2qmj 2qmj]
| maltase-glucoamylase
| ''Homo sapiens''
| acarbose
| '''Asp542'''
| Asp443
| <cite>Sim2008</cite>
|-
| [[GH32]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2add 2add]
| fructan β-(2,1)-fructosidase
| ''Cichorium intybus''
| sucrose
| '''Glu201'''
| Asp22
| <cite>Verhaest2007</cite>
|-
| [[GH33]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1s0i 1s0i]
| transsialidase
| ''Trypanosoma cruzi''
| sialyllactose
| '''Asp59'''
| Tyr342
| <cite>Amaya2004</cite>
|-
| [[GH34]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzw 4gzw]
| N2 neuraminidase
| ''Influenza'' A Tanzania/205/2010 H3N2
| α-{{Smallcaps|d}}-Neup5Ac-(2,3)-β-{{Smallcaps|d}}-Galp-(1,4)-β-{{Smallcaps|d}}-GlcpNAc
| '''Asp151'''
| Tyr406
| <cite>Zhu2012</cite>
|-
| [[GH35]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3ogv 3ogv]
| β-galactosidase
| ''Hypocrea jecorina''
| 2-phenylethyl 1-thio-β-{{Smallcaps|d}}-galactopyranoside
| '''Glu200'''
| Glu298
| <cite>Maksimainen2011</cite>
|-
| [[GH36]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4fns 4fns]
| β-galactosidase
| ''Geobacillus stearothermophilus''
| 1-deoxy galactonojirimycin
| '''Asp584'''
| Asp478
| <cite>Merceron2012</cite>
|-
| [[GH37]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2jf4 2jf4]
| trehalase
| ''Escherichia coli''
| validoxylamine
| '''Asp312'''
| Glu496
| <cite>Gibson2007</cite>
|-
| [[GH38]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3czn 3czn]
| Golgi α-mannosidase II
| ''Drosophila melanogaster''
| GlcNAcMan(5)GlcNAc(2)
| '''Asp341'''
| Asp204
| <cite>Shah2008</cite>
|-
| [[GH39]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2bfg 2bfg]
| β-xylosidase
| ''Geobacillus stearothermophilus''
| 2,5-dinitrophenyl-β-{{Smallcaps|d}}-xyloside
| '''Glu160'''
| Glu278
| <cite>Czjzek2005</cite>
|-
| [[GH42]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ucf 4ucf]
| β-galactosidase
| ''Bifidobacterium bifidum''
| {{Smallcaps|d}}-galactose
| '''Glu161'''
| Glu320
| <cite>Godoy2016</cite>
|-
| [[GH43]]
| F
| 5-fold β-propeller
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3akh 3akh]
| exo-1,5-α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces avermitilis''
| α-1,5-arabinofuranotriose
| '''Glu196'''
| Asp220
| <cite>Fujimoto2010</cite>
|-
| [[GH44]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2eqd 2eqd]
| endoglucanase
| ''Clostridium thermocellum''
| cellooctaose
| '''Glu186'''
| Glu359
| <cite>Kitago2007</cite>
|-
| [[GH45]]
| none
| 6-stranded β-barrel
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4eng 4eng]
| endo-1,4-glucanase
| ''Humicola insolens''
| cellohexaose
| '''Asp121'''
| Asp10
| <cite>Davies1996</cite>
|-
| [[GH46]]
| I
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4olt 4olt]
| chitosanase
| ''Microbacterium sp.'' OU01
| hexa-glucosamine
| '''Glu25'''
| Asp43
| <cite>Lyu2014</cite>
|-
| [[GH47]]
| none
| (α/α)7
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1x9d 1x9d]
| α-mannosidase I
| ''Homo sapiens''
| Me-2-S-(α-Man)-2-thio-α-Man
| '''Asp463'''
| Glu599
| <cite>Karaveg2005</cite>, <cite>Nerinckx2008</cite>
|-
| [[GH48]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH8''
|
|
|
|
|
|
|-
| [[GH49]]
| N
| β-helix
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH28''
|
|
|
|
|
|
|-
| [[GH50]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4bq5 4bq5]
| exo-β-agarase
| ''Saccharophagus degradans''
| neoagarotetraose
| '''Glu535'''
| Glu695
| <cite>Pluvinage2013</cite>
|-
| [[GH51]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1qw9 1qw9]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Geobacillus stearothermophilus''
| PNP-{{Smallcaps|l}}-arabinofuranoside
| '''Glu175'''
| Glu294
| <cite>Hoevel2003</cite>
|-
| [[GH52]]
| O
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4c1p 4c1p]
| β-xylosidase
| ''Geobacillus thermoglucosidasius''
| xylobiose
| '''Asp517'''
| Glu537
| <cite>Espina2014</cite>
|-
| [[GH53]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2ccr 2ccr]
| β-1,4-galactanase
| ''Bacillus licheniformis''
| galactotriose
| '''Glu165'''
| Glu263
| <cite>Le_Nours2009</cite>
|-
| [[GH54]]
| none
| β-sandwich
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1wd4 1wd4]
| α-{{Smallcaps|l}}-arabinofuranosidase B
| ''Aspergillus kawachii''
| {{Smallcaps|l}}-arabinofuranose
| '''Asp297'''
| Glu221
| <cite>Miyanaga2004</cite>
|-
| [[GH55]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4tz5 4tz5]
| exo-β-1,3-glucanase
| ''Streptomyces sp.'' SirexAA-E
| laminarihexaose
| '''Glu502'''
| unknown
| <cite>Bianchetti2015</cite>
|-
| [[GH56]]
| none
| (β/α)7
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1fcv 1fcv]
| hyaluronidase
| ''Apis mellifera''
| (hyaluron.)4
| '''Glu113'''
| internal
| <cite>Markovic-Housley2000</cite>
|-
| [[GH57]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1k1y 1k1y]
| glucanotransferase
| ''Thermococcus litoralis''
| acarbose
| '''Asp214'''
| Glu123
| <cite>Imamura2003</cite>
|-
| [[GH59]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ccc 4ccc]
| β-galactocerebrosidase
| ''Mus musculus''
| PNP-β-{{Smallcaps|d}}-galactoside
| '''Glu182'''
| Glu258
| <cite>Hill2013</cite>
|-
| [[GH62]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| ''predicted anti by clan''
| ''see at GH43''
|
|
|
|
|
|
|-
| [[GH63]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5ca3 5ca3]
| α-glucosidase
| ''Escherichia coli''
| glucose and lactose
| '''Asp501'''
| Glu727
| <cite>Miyazaki2016</cite>
|-
| [[GH65]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}4ktr 4ktr]
| 2-O-α-glucosylglycerol phosphorylase
| ''Bacillus selenitireducens''
| isofagomine
| '''Glu475'''
| phosphate
| <cite>Touhara2014</cite>
|-
| [[GH66]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5axh 5axh]
| dextranase
| ''Thermoanaerobacter pseudethanolicus''
| isomaltohexaose
| '''Glu374'''
| Asp312
| <cite>Suzuki2016</cite>
|-
| [[GH67]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1l8n 1l8n]
| α-glucuronidase
| ''Geobacillus stearothermophilus''
| 4-O-methyl-{{Smallcaps|d}}-glucuronic acid and xylotriose
| '''Glu286'''
| Asp364 Glu392
| <cite>Golan2004</cite>
|-
| [[GH68]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1pt2 1pt2]
| levansucrase
| ''Bacillus subtilis''
| sucrose
| '''Glu342'''
| Asp86
| <cite>Meng2003</cite>
|-
| [[GH70]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3aic 3aic]
| glucansucrase
| ''Streptococcus mutans''
| α-acarbose
| '''Glu515'''
| Asp477
| <cite>Ito2011</cite>
|-
| [[GH72]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w62 2w62]
| β-1,3-glucanotransferase
| ''Saccharomyces cerevisiae'' S288C
| laminaripentaose
| '''Glu176'''
| Glu275
| <cite>Hurtado-Gerrero2009</cite>
|-
| [[GH74]]
| none
| 7-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}2ebs 2ebs]
| cellobiohydrolase (OXG-RCBH)
| ''Geotrichum sp.'' m128
| xyloglucan heptasaccharide
| '''Asp465'''
| Asp35
| <cite>Yaoi2007</cite>
|-
| [[GH76]]
| none
| (α/α)6
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5agd 5agd]
| endo-α-1,6-mannanase
| ''Bacillus circulans''
| α-1,6-mannopentaose
| '''Asp125'''
| Asp124
| <cite>Thompson2015</cite>
|-
| [[GH77]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2oww 2oww]
| 4-α-glucanotransferase
| ''Thermus thermofilus''
| acarbose + 4-deoxy-α-{{Smallcaps|d}}-glucose
| '''Glu340'''
| Asp293
| <cite>Barends2007</cite>
|-
| [[GH78]]
| H
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3w5n 3w5n]
| α-{{Smallcaps|l}}-rhamnosidase
| ''Streptomyces avermitilis''
| {{Smallcaps|l}}-rhamnose
| '''Glu636'''
| Glu895
| <cite>Fujimoto2013</cite>
|-
| [[GH79]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5e9c 5e9c]
| heparanase
| ''Homo sapiens''
| heparin tetrasaccharide
| '''Glu225'''
| Glu343
| <cite>Wu2015</cite>
|-
| [[GH80]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH24''
|
|
|
|
|
|
|-
| [[GH81]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5t4g 5t4g]
| endo-β-1,3-glucanase
| ''Bacillus halodurans'' C-125
| laminarin
| '''Asp466'''
| Glu542
| <cite>Pluvinage2017</cite>
|-
| [[GH83]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH33''
|
|
|
|
|
|
|-
| [[GH84]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2chn 2chn]
| β-''N''-acetyl-glucosaminidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| NAG-thiazoline
| '''Glu242'''
| internal
| <cite>Dennis2006</cite>
|-
| [[GH85]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w92 2w92]
| endo-β-''N''-acetyl-glucosaminidase D
| ''Streptococcus pneumoniae'' TIGR4
| NAG-thiazoline
| '''Glu337'''
| internal
| <cite>Abbott2009</cite>
|-
| [[GH86]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4aw7 4aw7]
| β-porphyranase
| ''Bacteroides plebeius''
| porphyran fragment
| '''Glu152'''
| Glu279
| <cite>Hehemann_1_2012</cite>
|-
| [[GH89]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vcb 2vcb]
| α-''N''-acetyl-glucosaminidase
| ''Clostridium perfringens''
| PUGNAc
| '''Glu483'''
| Glu601
| <cite>Ficko-Blean2008</cite>
|-
| [[GH92]]
| none
| (α/α)6 and β-sandwich
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ww1 2ww1]
| α-1,2-mannosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| thiomannobioside
| '''Glu533'''
| Asp644 Asp642
| <cite>Zhu2009</cite>
|-
| [[GH93]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3a72 3a72]
| exo-arabinanase
| ''Penicillium chrysogenum''
| arabinobiose
| '''Glu246'''
| Glu174
| <cite>Sogabe2011</cite>
|-
| [[GH94]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4zli 4zli]
| cellobionic acid phosphorylase
| ''Saccharophagus degradans''
| 3-O-β-{{Smallcaps|d}}-glucopyranosyl-α-{{Smallcaps|d}}-glucopyranuronic acid
| '''Asp472'''
| phosphate
| <cite>Nam2015</cite>
|-
| [[GH95]]
| none
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ead 2ead]
| α-1,2-{{Smallcaps|l}}-fucosidase
| ''Bifidobacterium bifidum''
| Fuc-α-1,2-Gal
| '''Glu566'''
| Asn423 Asp766
| <cite>Nagae2007</cite>
|-
| [[GH97]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining + inverting
| '''''anti'''''
| [{{PDBlink}}2zq0 2zq0]
| α-glucosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| acarbose
| '''Glu532'''
| Glu508
| <cite>Kitamura2008</cite>
|-
| [[GH98]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2wmg 2wmg]
| endo-β-1,4-galactosidase
| ''Streptococcus pneumoniae''
| A-LewisY pentasaccharide
| '''Glu158'''
| Asp251 Glu301
| <cite>Higgins2009</cite>
|-
| [[GH99]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ad4 4ad4]
| endo-α-mannosidase
| ''Bacteroides xylanisolvens''
| glucose-1,3-isofagomine and α-1,2- mannobiose
| '''Glu336'''
| debated
| <cite>Thompson2012</cite>
|-
| [[GH100]]
| none
| (α/α)6 core
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5gop 5gop]
| invertase
| ''Anabaena (Nostoc) sp.'' pcc7120
| sucrose
| '''Asp188'''
| Glu414
| <cite>Xie2016</cite>
|-
| [[GH102]]
| none
| double-ψ β-barrel
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}2pi8 2pi8]
| lytic transglycosylase A
| ''Escherichia coli''
| chitohexaose
| '''Asp308'''
| none
| <cite>van_Straaten2007</cite>
|-
| [[GH103]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1d0k 1d0k]
| lytic transglycosylase SLT35
| ''Escherichia coli''
| murodipeptides
| '''Glu162'''
| internal
| <cite>van_Asselt2000</cite>
|-
| [[GH106]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5mwk 5mwk]
| α-{{Smallcaps|l}}-rhamnosidase BT_0986
| ''Bacteroides thetaiotaomicron''
| pectin heptasaccharide
| '''Glu461'''
| Glu593 or Glu561
| <cite>Ndeh2017</cite>
|-
| [[GH107]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| ''predicted syn by clan''
| ''see at GH29''
|
|
|
|
|
|
|-
| [[GH113]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4cd8 4cd8]
| β-mannanase
| ''Alicyclobacillus acidocaldarius''
| mannobioimidazole
| '''Glu151'''
| Glu231
| <cite>Williams2014</cite>
|-
| [[GH116]]
| O
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at GH52''
|
|
|
|
|
|
|-
| [[GH117]]
| none
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}4ak7 4ak7]
| α-1,3-3,6-anhydro-{{Smallcaps|l}}-galactosidase
| ''Bacteroides plebeius''
| neoagarobiose
| '''His302'''
| Asp90
| <cite>Hehemann_2_2012</cite>
|-
| [[GH120]]
| none
| parallel β-helix and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3vsv 3vsv]
| β-xylosidase XylC
| ''Thermoanaerobacterium saccharolyticum'' JW/SL-YS485
| {{Smallcaps|d}}-xylose
| '''Glu405'''
| Asp382
| <cite>Huang2012</cite>
|-
| [[GH123]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5fr0 5fr0]
| exo-β-N-acetyl-galactosaminidase
| ''Clostridium perfringens''
| ''N''-difluoroacetyl-{{Smallcaps|d}}-galactosamine
| '''Glu345'''
| internal
| <cite>Noach2016</cite>
|-
| [[GH125]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5m7y 5m7y]
| exo-α-1,6-mannosidase
| ''Clostridium perfringens''
| 1,6-α-mannotriose
| '''Asp220'''
| Glu393
| <cite>Alonso-Gil2016</cite>
|-
| [[GH127]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3wrg 3wrg]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bifidobacterium longum''
| {{Smallcaps|l}}-arabinose
| '''Glu322'''
| Cys417
| <cite>Huang2014</cite>
|-
| [[GH128]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH1''
|
|
|
|
|
|
|-
| [[GH130]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5b0s 5b0s]
| β-1,2-mannobiose phosphorylase
| ''Listeria innocua''
| β-1,2-mannotriose
| '''Asp141''' relay
| phosphate
| <cite>Tsuda2015</cite>
|-
| [[GH134]]
| none
| β + α
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5jug 5jug]
| β-mannanase
| ''Streptomyces sp.''
| mannopentaose
| '''Glu45'''
| Asp57
| <cite>Jin2016</cite>
|-
| [[GH136]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}5gqf 5gqf]
| lacto-N-biosidase
| ''Bifidobacterium longum''
| lacto-N-biose
| '''Asp411'''
| Asp418
| <cite>Yamada2017</cite>
|-
| [[GH137]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|l}}
| unknown
| '''''anti'''''
| [{{PDBlink}}5mui 5mui]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0996
| ''Bacteroides thetaiotaomicron''
| pectin oligosaccharide
| '''Glu240'''
| Glu159
| <cite>Ndeh2017</cite>

|-
| [[GH138]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}6hzg 6hzg]
| α-1,2-{{Smallcaps|d}}-galacturonidase
| ''Bacteroides paurosaccharolyticus''
| alpha-{{Smallcaps|d}}-galactopyranuronic
| '''Glu294'''
| Glu361
| <cite>Labourel2019</cite>
|-
| [[GH146]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5opj 5opj]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0349
| ''Bacteroides thetaiotaomicron''
| {{Smallcaps|l}}-arabinose
| '''Glu320'''
| Cys416
| <cite>Luis2018</cite>
|-
| [[GH147]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH148]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH149]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH157]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH158]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH161]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH162]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}6imw 5imw]
| endo-β-1,2-glucanase
| ''Talaromyces funiculosus''
| beta-1,2-glucan
| '''Glu262'''
| Asp446
| <cite>Tanaka2019</cite>
|-
| [http://www.cazy.org/GH0.html n.c.*]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2vjj 2vjj]
| endo-α-N-acetylglucosaminidase
| Bacteriophage HK620
| O18A1 O-antigen hexasaccharide
| '''Asp339'''
| Glu372
| <cite>Barbirz2008</cite>
|}
<nowiki>*</nowiki> n.c.: Found among the collection of [http://www.cazy.org/GH0.html non-classified GH sequences in the CAZy Database].

== References ==

<biblio>
# HeightmanVasella1999 Heightman TD and Vasella AT. ''Recent Insights into Inhibition, Structure, and Mechanism of Configuration-Retaining Glycosidases.'' Angew Chem Int Ed. 1999 38(6):750-770. [http://www3.interscience.wiley.com/journal/55000581/abstract Article online].
# Nerinckx2005 pmid=15642336
# Wu2012 pmid=23137336
# Perez1978 Pérez S and Marchessault RH. ''The exo-anomeric effect: experimental evidence from crystal structures.'' Carbohydr res. 1978 65:114-120. [http://dx.doi.org/10.1016/S0008-6215(00)84218-4 DOI:10.1016/S0008-6215(00)84218-4]
# Cramer1997 Cramer CJ, Truhlar DG, and French AD. ''Exo-anomeric effects on energies and geometries of different conformations of glucose and related systems in the gas phase and aqueous solution.'' Carbohydr res. 1997 298:1-14. [http://dx.doi.org/10.1016/S0008-6215(96)00297-2 DOI:10.1016/S0008-6215(96)00297-2]
# Johnson2009 pmid=19733839
# Alonso2016 pmid=26889578
# Gloster2006 pmid=17002288
# van_Bueren2009 pmid=18976664
# Hrmova2001 pmid=11709165
# Varrot2003 pmid=12595701
# Zhou1999 pmid=10508787
# Sulzenbacher1999 pmid=10200171
# Urbanikova2011 pmid=21501386
# Guerin2002 pmid=11884144
# Schubot2004 pmid=14756552
# Suzuki2009 pmid=19279191
# Wan2014 pmid=24419374
# Sandgren2004 pmid=15364577
# Uitdehaag1999 pmid=10331869
# Miyake2003 pmid=12741813
# Harris1993 pmid=8431441
# Allouch2004 pmid=15062085

# Wojtkowiak2013 pmid=23275163
# Papanikolau2001 pmid=11560481

# Prag2000 pmid=10884356
# Vocadlo2001 pmid=11518970
# Karlsen1996 pmid=15299731
# Baldwin1993 pmid=8259514
# Cartmell2008 pmid=18799462
# Fernandez-Leiro2010 pmid=20592022
# Abbott2007 pmid=17397864
# Sakurama2012 pmid=22451675
# Sim2008 pmid=18036614
# Verhaest2007 pmid=17335500
# Amaya2004 pmid=15130470
# Zhu2012 pmid=23015718
# Maksimainen2011 pmid=21130883
# Merceron2012 pmid=23012371
# Gibson2007 pmid=17455176
# Shah2008 pmid=18599462
# Czjzek2005 pmid=16212978
# Godoy2016 pmid=27685756
# Fujimoto2010 pmid=20739278
# Kitago2007 pmid=17905739
# Davies1996 pmid=15299721
# Lyu2014 pmid=24766439
# Karaveg2005 pmid=15713668
# Nerinckx2008 pmid=18619586
# Pluvinage2013 pmid=23921382
# Hoevel2003 pmid=14517232
# Espina2014 pmid=24816105
# Le_Nours2009 pmid=19089956
# Miyanaga2004 pmid=15292273
# Bianchetti2015 pmid=25752603
# Markovic-Housley2000 pmid=11080624
# Imamura2003 pmid=12618437
# Hill2013 pmid=24297913
# Miyazaki2016 pmid=27688023
# Touhara2014 pmid=24828502
# Suzuki2016 pmid=26494689
# Golan2004 pmid=14573597
# Meng2003 pmid=14517548
# Ito2011 pmid=21354427
# Hurtado-Gerrero2009 pmid=19097997
# Yaoi2007 pmid=17498741
# Thompson2015 pmid=25772148
# Barends2007 pmid=17420245
# Fujimoto2013 pmid=23486481
# Wu2015 pmid=26575439
# Pluvinage2017 pmid=28781080
# Dennis2006 pmid=16565725
# Abbott2009 pmid=19181667
# Hehemann_1_2012 pmid=23150581
# Ficko-Blean2008 pmid=18443291
# Zhu2009 pmid=20081828
# Sogabe2011 pmid=21543843
# Nam2015 pmid=26041776
# Nagae2007 pmid=17459873
# Kitamura2008 pmid=18981178
# Higgins2009 pmid=19608744
# van_Straaten2007 pmid=17502382
# van_Asselt2000 pmid=10684641
# Ndeh2017 pmid=28329766
# Labourel2019 pmid=30877196

# Luis2018 pmid=29255254
# Jin2016 Jin Y, Petricevic M, John A, Raich L, Jenkins H, Portela De Souza L, Cuskin F, Gilbert HJ, Rovira C, Goddard-Borger ED, Williams SJ, and Davies GJ. ''A β-Mannanase with a Lysozyme-like Fold and a Novel Molecular Catalytic Mechanism.'' ACS Cent Sci. 2016 Nov [http://dx.doi.org/10.1021/acscentsci.6b00232 DOI:10.1021/acscentsci.6b00232]
# Yamada2017 pmid=28392148
# Ohnuma2014 pmid=24582745
# Thompson2012 pmid=22219371
# Xie2016 pmid=27777307
# Williams2014 pmid=24339341
# Hehemann_2_2012 pmid=22393053
# Huang2012 pmid=22992047
# Noach2016 pmid=27038508
# Alonso-Gil2016 pmid=28026180
# Huang2014 Huang CH, Zhu Z, Cheng YS, Chan HC, Ko TP, Chen CC, Wang I, Ho MR, Hsu ST, Zeng YF, Huang YN, Liu JR, Guo RT. ''Structure and Catalytic Mechanism of a Glycoside Hydrolase Family-127 β-L-Arabinofuranosidase (HypBA1).'' J Bioprocess Biotech. 2014 4:171 [http://dx.doi.org/10.4172/2155-9821.1000171 DOI:10.4172/2155-9821.1000171]
# Tsuda2015 pmid=26632508
# Barbirz2008 pmid=18547389
# Tanaka2019 pmid=30926603

</biblio>

[[Category:Definitions and explanations]]

Syn/anti lateral protonation

2019-04-29T15:12:35Z

Wim Nerinckx: GH138 and GH162 syn

{{CuratorApproved}}
* [[Author]]: ^^^Wim Nerinckx^^^
* [[Responsible Curator]]: ^^^Spencer Williams^^^

----

== Overview ==

This page provides a table that summarizes the spatial positioning of the catalytic [[general acid]] residue in the active sites of [[glycoside hydrolase]]s, relative to the substrate. The table below updates those found in the seminal paper on this concept by Heightman and Vasella <cite>HeightmanVasella1999</cite>, and a following paper by Nerinckx ''et al.'' <cite>Nerinckx2005</cite>.

== Background ==

The ''"not from above, but from the side"'' concept of semi-lateral glycosidic oxygen [[General_acid/base|protonation]] by [[glycoside hydrolase]]s was introduced by Heightman and Vasella <cite>HeightmanVasella1999</cite>. It was originally only described for [[Anomeric centre (alpha and beta)|beta]]-equatorial [[glycoside hydrolase]]s, but appears to be equally applicable to enzymes acting on an [[Anomeric centre (alpha and beta)|alpha]]-axial glycosidic bond <cite>Nerinckx2005</cite>. When dividing [[Sub-site nomenclature|subsite -1]] into half-spaces by a plane defined by the glycosidic oxygen and C1' and H1' of the –1 glycoside, many ligand-complexed structures reveal that the [[General_acid/base|proton donor]] is positioned either in the ''syn'' half-space (near the ring-oxygen of the –1 glycoside), or in the ''anti'' half-space (on the opposite side of the ring-oxygen). Members of the same GH [[Families|family]] appear to share a common ''syn'' or ''anti'' [[General_acid/base|protonator]] arrangement and further, this specificity appears to be preserved within [[Clans|Clans]] of [[Families|families]]. This page's compilation of [[Sub-site nomenclature|subsite -1]] occupied complexes shows that about 70% of all GH [[Families|families]] are ''anti'' [[General_acid/base|protonators]].

Closer inspection of crystal structures of [[Sub-site nomenclature|–1/+1 subsite]]-spanning substrates, or substrate-analogue ligands, in complex with enzymes reveals a further intriguing corollary <cite>Nerinckx2005 Wu2012</cite>. In substrate-bound complexes with ''anti'' [[General_acid/base|protonating]] GH enzymes, the scissile [[Anomeric centre (alpha and beta)|anomeric bond]] (often studied using the thio-analogue) shows a dihedral angle φ (O5'-C1'-[O,S]x-Cx) that is in the lowest-energy synclinal (gauche) conformation. The rationale for this is that a minus synclinal dihedral angle φ for an equatorial glycosidic bond, or plus synclinal for an axial glycosidic bond <cite>Perez1978</cite>, allows for hyperconjugative overlap of the C1'-O5' antibonding orbital with an antiperiplanar-oriented lone pair orbital lobe of the glycosidic oxygen, thereby creating partial double bond character and stabilization of the glycosidic bond by 4–5 kcal/mol; this ground-state stabilizing phenomenon is known as the ‘exo-anomeric effect’ <cite>Cramer1997 Johnson2009 Alonso2016</cite>. ''Anti'' [[General_acid/base|protonation]] occurs on the glycosidic oxygen’s antiperiplanar lone pair, thereby removing the stabilizing exo-anomeric effect. This suggests that ''anti'' [[General_acid/base|protonation]] is an enzymic approach for lowering the activation barrier leading to the [[Transition state|transition state]] (Figure 1 centre).

''Syn'' [[General_acid/base|protonating]] [[glycoside hydrolase]]s apparently make use of a different approach <cite>Nerinckx2005 Wu2012</cite>. In many [[Sub-site nomenclature|–1/+1 subsite]]-spanning ligand complexes, the dihedral angle φ of the scissile anomeric bond has been rotated away from its lowest-energy synclinal position: clockwise to minus-anticlinal or antiperiplanar for beta-equatorial; counterclockwise to plus-anticlinal or antiperiplanar for alpha-axial [[Anomeric centre (alpha and beta)|anomeric bonds]]. This removes the hyperconjugative overlap and thus also the stabilizing exo-anomeric effect. And because of this rotation, a lone pair of the glycosidic oxygen is directed into the ''syn'' half-space, allowing it to be protonated by the ''syn''-positioned [[General_acid/base|proton donor]] (Figure 1 right).

[[File:Syn_anti.jpg|800px|thumb|center|Figure 1. Newman projections, with the glycosidic oxygen as proximal atom and the anomeric carbon as distal atom, showing ''anti'' (centre) versus ''syn'' (right) semi-lateral [[General_acid/base|protonation]] in beta-equatorial (top) and alpha-axial (bottom) [[glycoside hydrolase]]s. The indicated φ is the dihedral angle for O5'-C1'-O4-C4.]]

== Table of ''syn/anti'' protonation examples ==

This table contains only one example per GH [[Families|family]] of a ligand-complexed protein structure where the ''syn'' or ''anti'' positioning of the [[General_acid/base|proton donor]] can be clearly observed; other examples may be available on a [[Families|family-by-family]] basis. The reader is thus advised to consult the [http://www.cazy.org/fam/acc_GH.html#table CAZy database] for a current, comprehensive list of CAZyme structures. Where available, the selected examples are Michaelis-type complexes with the ligand spanning the [[Sub-site nomenclature|-1/+1 subsites]], since these have an intact glycosidic or thioglycosidic bond, or are ''N''-analogs of the substrate (''e.g.'' acarbose). In some examples, the [[General_acid/base|proton donor]] has been mutated (''e.g.'', to the corresponding amide or to an alanine), and in those cases one may wish to look at a superposition of the given PDB example with the structure of the native enzyme. If a Michaelis-type complex is not yet available, the second and third example choices, respectively, are trapped glycosyl-enzyme [[intermediate]]s and product complexes where [[Sub-site nomenclature|subsite -1]] is occupied.

''Please also be aware that this is a large table with many data. Please contact the page Author or Responsible Curator with corrections.''

=== Table ===
This table can be re-sorted by clicking on the icons in the header (''javascript must be turned on in your browser''). To reset the page to be sorted by GH family, click the ''View'' tab at the very top of the page.

{| {{Prettytable}} class="sortable"
|- valign="top"
! '''Family'''
! '''Clan'''
! '''Structure fold '''
! '''Anomeric specificity'''
! '''Mechanism'''
! '''''Syn/anti'' protonator'''
! '''Example PDB ID'''
! '''Enzyme'''
! '''Organism'''
! '''Ligand'''
! '''General acid'''
! '''Nucleophile or General base'''
! '''Reference'''
|-
| [[GH1]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2cer 2cer]
| β-glycosidase S
| ''Sulfolobus solfataricus'' P2
| phenethyl glucoimidazole
| '''Glu206'''
| Glu387
| <cite>Gloster2006</cite>
|-
| [[GH2]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vzu 2vzu]
| exo-β-glucosaminidase
| ''Amicolatopsis orientalis''
| PNP-β-{{Smallcaps|d}}-glucosamine
| '''Glu469'''
| Glu541
| <cite>van_Bueren2009</cite>
|-
| [[GH3]]
| none
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1iex 1iex]
| exo-1,3-1,4-glucanase
| ''Hordeum vulgare''
| thiocellobiose
| '''Glu491'''
| Asp285
| <cite>Hrmova2001</cite>
|-
| [[GH5]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1h2j 1h2j]
| endo-β-1,4-glucanase
| ''Bacillus agaradhaerens''
| 2',4'-DNP-2-F-cellobioside
| '''Glu129'''
| Glu228
| <cite>Varrot2003</cite>
|-
| [[GH6]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1qjw 1qjw]
| cellobiohydrolase 2
| ''Hypocrea jecorina''
| (Glc)2-S-(Glc)2
| '''Asp221'''
| debated
| <cite>Zhou1999</cite>
|-
| [[GH7]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1ovw 1ovw]
| endo-1,4-glucanase
| ''Fusarium oxysporum''
| thio-(Glc)5
| '''Glu202'''
| Glu197
| <cite>Sulzenbacher1999</cite>
|-
| [[GH8]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1kwf 1kwf]
| endo-1,4-glucanase
| ''Clostridium thermocellum''
| cellopentaose
| '''Glu95'''
| Asp278
| <cite>Guerin2002</cite>
|-
| [[GH9]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1rq5 1rq5]
| cellobiohydrolase
| ''Clostridium thermocellum''
| cellotetraose
| '''Glu795'''
| Asp383
| <cite>Schubot2004</cite>
|-
| [[GH10]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2d24 2d24]
| β-1,4-xylanase
| ''Streptomyces olivaceoviridis'' E-86
| xylopentaose
| '''Glu128'''
| Glu236
| <cite>Suzuki2009</cite>
|-
| [[GH11]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}4hk8 4hk8]
| endo-β-1,4-xylanase
| ''Hypocrea jecorina''
| xylohexaose
| '''Glu177'''
| Glu86
| <cite>Wan2014</cite>
|-
| [[GH12]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1w2u 1w2u]
| endoglucanase
| ''Humicola grisea''
| thiocellotetraose
| '''Glu205'''
| Glu120
| <cite>Sandgren2004</cite>
|-
| [[GH13]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1cxk 1cxk]
| β-cyclodextrin glucanotransferase
| ''Bacillus circulans''
| maltononaose
| '''Glu257'''
| Asp229
| <cite>Uitdehaag1999</cite>
|-
| [[GH14]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1itc 1itc]
| β-amylase
| ''Bacillus cereus''
| maltopentaose
| '''Glu172'''
| Glu367
| <cite>Miyake2003</cite>
|-
| [[GH15]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1dog 1dog]
| glucoamylase
| ''Aspergillus awamori''
| 1-deoxynojirimycin
| '''Glu179'''
| Glu400
| <cite>Harris1993</cite>
|-
| [[GH16]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1urx 1urx]
| β-agarase A
| ''Zobellia galactanivorans''
| oligoagarose
| '''Glu152'''
| Glu147
| <cite>Allouch2004</cite>
|-
| [[GH17]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH1''
|
|
|
|
|
|
|-
| [[GH18]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1ffr 1ffr]
| chitinase A
| ''Serratia marcescens''
| (NAG)6
| '''Glu315'''
| internal
| <cite>Papanikolau2001</cite>
|-
| [[GH19]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}3wh1 3wh1]
| chitinase
| ''Bryum coronatum''
| (GlcNAc)4
| '''Glu61'''
| Glu70
| <cite>Ohnuma2014</cite>
|-
| [[GH20]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1c7s 1c7s]
| chitobiase
| ''Serratia marcescens''
| chitobiose
| '''Glu540'''
| internal
| <cite>Prag2000</cite>
|-
| [[GH22]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1h6m 1h6m]
| lysozyme C
| ''Gallus gallus''
| Chit-2-F-chitosyl
| '''Glu35'''
| Asp52
| <cite>Vocadlo2001</cite>
|-
| [[GH23]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1lsp 1lsp]
| lysozyme G
| ''Cygnus atratus''
| Bulgecin A
| '''Glu73'''
| internal
| <cite>Karlsen1996</cite>
|-
| [[GH24]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}148l 148l]
| lysozyme E
| Bacteriophage T4
| chitobiosyl
| '''Glu11'''
| Glu26
| <cite>Baldwin1993</cite>
|-
| [[GH26]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vx6 2vx6]
| exo-β-mannanase
| ''Cellvibrio japonicus'' Ueda107
| Gal1Man4
| '''Glu221'''
| Glu338
| <cite>Cartmell2008</cite>
|-
| [[GH27]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}} / beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3lrm 3lrm]
| α-galactosidase
| ''Saccharomyces cerevisiae''
| raffinose
| '''Asp209'''
| Asp141
| <cite>Fernandez-Leiro2010</cite>
|-
| [[GH28]]
| N
| β-helix
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}2uvf 2uvf]
| exo-polygalacturonosidase
| ''Yersinia enterocolitica'' ATCC9610D
| digalacturonic acid
| '''Asp402'''
| Asp381 Asp403
| <cite>Abbott2007</cite>
|-
| [[GH29]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| '''''syn'''''
| [{{PDBlink}}3uet 3uet]
| α-1,3/4-fucosidase
| ''Bifidobacterium longum'' subsp. infantis
| lacto-''N''-fucopentaose II
| '''Glu217'''
| Asp172
| <cite>Sakurama2012</cite>
|-
| [[GH30]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2y24 2y24]
| glucurono-xylanase
| ''Dickea chrysanthemi'' D1
| glucuronoxylan tetrasaccharide
| '''Glu163'''
| Glu253
| <cite>Urbanikova2011</cite>
|-
| [[GH31]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2qmj 2qmj]
| maltase-glucoamylase
| ''Homo sapiens''
| acarbose
| '''Asp542'''
| Asp443
| <cite>Sim2008</cite>
|-
| [[GH32]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2add 2add]
| fructan β-(2,1)-fructosidase
| ''Cichorium intybus''
| sucrose
| '''Glu201'''
| Asp22
| <cite>Verhaest2007</cite>
|-
| [[GH33]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1s0i 1s0i]
| transsialidase
| ''Trypanosoma cruzi''
| sialyllactose
| '''Asp59'''
| Tyr342
| <cite>Amaya2004</cite>
|-
| [[GH34]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzw 4gzw]
| N2 neuraminidase
| ''Influenza'' A Tanzania/205/2010 H3N2
| α-{{Smallcaps|d}}-Neup5Ac-(2,3)-β-{{Smallcaps|d}}-Galp-(1,4)-β-{{Smallcaps|d}}-GlcpNAc
| '''Asp151'''
| Tyr406
| <cite>Zhu2012</cite>
|-
| [[GH35]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3ogv 3ogv]
| β-galactosidase
| ''Hypocrea jecorina''
| 2-phenylethyl 1-thio-β-{{Smallcaps|d}}-galactopyranoside
| '''Glu200'''
| Glu298
| <cite>Maksimainen2011</cite>
|-
| [[GH36]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4fns 4fns]
| β-galactosidase
| ''Geobacillus stearothermophilus''
| 1-deoxy galactonojirimycin
| '''Asp584'''
| Asp478
| <cite>Merceron2012</cite>
|-
| [[GH37]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2jf4 2jf4]
| trehalase
| ''Escherichia coli''
| validoxylamine
| '''Asp312'''
| Glu496
| <cite>Gibson2007</cite>
|-
| [[GH38]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3czn 3czn]
| Golgi α-mannosidase II
| ''Drosophila melanogaster''
| GlcNAcMan(5)GlcNAc(2)
| '''Asp341'''
| Asp204
| <cite>Shah2008</cite>
|-
| [[GH39]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2bfg 2bfg]
| β-xylosidase
| ''Geobacillus stearothermophilus''
| 2,5-dinitrophenyl-β-{{Smallcaps|d}}-xyloside
| '''Glu160'''
| Glu278
| <cite>Czjzek2005</cite>
|-
| [[GH42]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ucf 4ucf]
| β-galactosidase
| ''Bifidobacterium bifidum''
| {{Smallcaps|d}}-galactose
| '''Glu161'''
| Glu320
| <cite>Godoy2016</cite>
|-
| [[GH43]]
| F
| 5-fold β-propeller
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3akh 3akh]
| exo-1,5-α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces avermitilis''
| α-1,5-arabinofuranotriose
| '''Glu196'''
| Asp220
| <cite>Fujimoto2010</cite>
|-
| [[GH44]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2eqd 2eqd]
| endoglucanase
| ''Clostridium thermocellum''
| cellooctaose
| '''Glu186'''
| Glu359
| <cite>Kitago2007</cite>
|-
| [[GH45]]
| none
| 6-stranded β-barrel
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4eng 4eng]
| endo-1,4-glucanase
| ''Humicola insolens''
| cellohexaose
| '''Asp121'''
| Asp10
| <cite>Davies1996</cite>
|-
| [[GH46]]
| I
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4olt 4olt]
| chitosanase
| ''Microbacterium sp.'' OU01
| hexa-glucosamine
| '''Glu25'''
| Asp43
| <cite>Lyu2014</cite>
|-
| [[GH47]]
| none
| (α/α)7
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1x9d 1x9d]
| α-mannosidase I
| ''Homo sapiens''
| Me-2-S-(α-Man)-2-thio-α-Man
| '''Asp463'''
| Glu599
| <cite>Karaveg2005</cite>, <cite>Nerinckx2008</cite>
|-
| [[GH48]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH8''
|
|
|
|
|
|
|-
| [[GH49]]
| N
| β-helix
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH28''
|
|
|
|
|
|
|-
| [[GH50]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4bq5 4bq5]
| exo-β-agarase
| ''Saccharophagus degradans''
| neoagarotetraose
| '''Glu535'''
| Glu695
| <cite>Pluvinage2013</cite>
|-
| [[GH51]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1qw9 1qw9]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Geobacillus stearothermophilus''
| PNP-{{Smallcaps|l}}-arabinofuranoside
| '''Glu175'''
| Glu294
| <cite>Hoevel2003</cite>
|-
| [[GH52]]
| O
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4c1p 4c1p]
| β-xylosidase
| ''Geobacillus thermoglucosidasius''
| xylobiose
| '''Asp517'''
| Glu537
| <cite>Espina2014</cite>
|-
| [[GH53]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2ccr 2ccr]
| β-1,4-galactanase
| ''Bacillus licheniformis''
| galactotriose
| '''Glu165'''
| Glu263
| <cite>Le_Nours2009</cite>
|-
| [[GH54]]
| none
| β-sandwich
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1wd4 1wd4]
| α-{{Smallcaps|l}}-arabinofuranosidase B
| ''Aspergillus kawachii''
| {{Smallcaps|l}}-arabinofuranose
| '''Asp297'''
| Glu221
| <cite>Miyanaga2004</cite>
|-
| [[GH55]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4tz5 4tz5]
| exo-β-1,3-glucanase
| ''Streptomyces sp.'' SirexAA-E
| laminarihexaose
| '''Glu502'''
| unknown
| <cite>Bianchetti2015</cite>
|-
| [[GH56]]
| none
| (β/α)7
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1fcv 1fcv]
| hyaluronidase
| ''Apis mellifera''
| (hyaluron.)4
| '''Glu113'''
| internal
| <cite>Markovic-Housley2000</cite>
|-
| [[GH57]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1k1y 1k1y]
| glucanotransferase
| ''Thermococcus litoralis''
| acarbose
| '''Asp214'''
| Glu123
| <cite>Imamura2003</cite>
|-
| [[GH59]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ccc 4ccc]
| β-galactocerebrosidase
| ''Mus musculus''
| PNP-β-{{Smallcaps|d}}-galactoside
| '''Glu182'''
| Glu258
| <cite>Hill2013</cite>
|-
| [[GH62]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| ''predicted anti by clan''
| ''see at GH43''
|
|
|
|
|
|
|-
| [[GH63]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5ca3 5ca3]
| α-glucosidase
| ''Escherichia coli''
| glucose and lactose
| '''Asp501'''
| Glu727
| <cite>Miyazaki2016</cite>
|-
| [[GH65]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}4ktr 4ktr]
| 2-O-α-glucosylglycerol phosphorylase
| ''Bacillus selenitireducens''
| isofagomine
| '''Glu475'''
| phosphate
| <cite>Touhara2014</cite>
|-
| [[GH66]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5axh 5axh]
| dextranase
| ''Thermoanaerobacter pseudethanolicus''
| isomaltohexaose
| '''Glu374'''
| Asp312
| <cite>Suzuki2016</cite>
|-
| [[GH67]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1l8n 1l8n]
| α-glucuronidase
| ''Geobacillus stearothermophilus''
| 4-O-methyl-{{Smallcaps|d}}-glucuronic acid and xylotriose
| '''Glu286'''
| Asp364 Glu392
| <cite>Golan2004</cite>
|-
| [[GH68]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1pt2 1pt2]
| levansucrase
| ''Bacillus subtilis''
| sucrose
| '''Glu342'''
| Asp86
| <cite>Meng2003</cite>
|-
| [[GH70]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3aic 3aic]
| glucansucrase
| ''Streptococcus mutans''
| α-acarbose
| '''Glu515'''
| Asp477
| <cite>Ito2011</cite>
|-
| [[GH72]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w62 2w62]
| β-1,3-glucanotransferase
| ''Saccharomyces cerevisiae'' S288C
| laminaripentaose
| '''Glu176'''
| Glu275
| <cite>Hurtado-Gerrero2009</cite>
|-
| [[GH74]]
| none
| 7-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}2ebs 2ebs]
| cellobiohydrolase (OXG-RCBH)
| ''Geotrichum sp.'' m128
| xyloglucan heptasaccharide
| '''Asp465'''
| Asp35
| <cite>Yaoi2007</cite>
|-
| [[GH76]]
| none
| (α/α)6
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5agd 5agd]
| endo-α-1,6-mannanase
| ''Bacillus circulans''
| α-1,6-mannopentaose
| '''Asp125'''
| Asp124
| <cite>Thompson2015</cite>
|-
| [[GH77]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2oww 2oww]
| 4-α-glucanotransferase
| ''Thermus thermofilus''
| acarbose + 4-deoxy-α-{{Smallcaps|d}}-glucose
| '''Glu340'''
| Asp293
| <cite>Barends2007</cite>
|-
| [[GH78]]
| H
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3w5n 3w5n]
| α-{{Smallcaps|l}}-rhamnosidase
| ''Streptomyces avermitilis''
| {{Smallcaps|l}}-rhamnose
| '''Glu636'''
| Glu895
| <cite>Fujimoto2013</cite>
|-
| [[GH79]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5e9c 5e9c]
| heparanase
| ''Homo sapiens''
| heparin tetrasaccharide
| '''Glu225'''
| Glu343
| <cite>Wu2015</cite>
|-
| [[GH80]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH24''
|
|
|
|
|
|
|-
| [[GH81]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5t4g 5t4g]
| endo-β-1,3-glucanase
| ''Bacillus halodurans'' C-125
| laminarin
| '''Asp466'''
| Glu542
| <cite>Pluvinage2017</cite>
|-
| [[GH83]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH33''
|
|
|
|
|
|
|-
| [[GH84]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2chn 2chn]
| β-''N''-acetyl-glucosaminidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| NAG-thiazoline
| '''Glu242'''
| internal
| <cite>Dennis2006</cite>
|-
| [[GH85]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w92 2w92]
| endo-β-''N''-acetyl-glucosaminidase D
| ''Streptococcus pneumoniae'' TIGR4
| NAG-thiazoline
| '''Glu337'''
| internal
| <cite>Abbott2009</cite>
|-
| [[GH86]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4aw7 4aw7]
| β-porphyranase
| ''Bacteroides plebeius''
| porphyran fragment
| '''Glu152'''
| Glu279
| <cite>Hehemann_1_2012</cite>
|-
| [[GH89]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vcb 2vcb]
| α-''N''-acetyl-glucosaminidase
| ''Clostridium perfringens''
| PUGNAc
| '''Glu483'''
| Glu601
| <cite>Ficko-Blean2008</cite>
|-
| [[GH92]]
| none
| (α/α)6 and β-sandwich
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ww1 2ww1]
| α-1,2-mannosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| thiomannobioside
| '''Glu533'''
| Asp644 Asp642
| <cite>Zhu2009</cite>
|-
| [[GH93]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3a72 3a72]
| exo-arabinanase
| ''Penicillium chrysogenum''
| arabinobiose
| '''Glu246'''
| Glu174
| <cite>Sogabe2011</cite>
|-
| [[GH94]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4zli 4zli]
| cellobionic acid phosphorylase
| ''Saccharophagus degradans''
| 3-O-β-{{Smallcaps|d}}-glucopyranosyl-α-{{Smallcaps|d}}-glucopyranuronic acid
| '''Asp472'''
| phosphate
| <cite>Nam2015</cite>
|-
| [[GH95]]
| none
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ead 2ead]
| α-1,2-{{Smallcaps|l}}-fucosidase
| ''Bifidobacterium bifidum''
| Fuc-α-1,2-Gal
| '''Glu566'''
| Asn423 Asp766
| <cite>Nagae2007</cite>
|-
| [[GH97]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining + inverting
| '''''anti'''''
| [{{PDBlink}}2zq0 2zq0]
| α-glucosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| acarbose
| '''Glu532'''
| Glu508
| <cite>Kitamura2008</cite>
|-
| [[GH98]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2wmg 2wmg]
| endo-β-1,4-galactosidase
| ''Streptococcus pneumoniae''
| A-LewisY pentasaccharide
| '''Glu158'''
| Asp251 Glu301
| <cite>Higgins2009</cite>
|-
| [[GH99]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ad4 4ad4]
| endo-α-mannosidase
| ''Bacteroides xylanisolvens''
| glucose-1,3-isofagomine and α-1,2- mannobiose
| '''Glu336'''
| debated
| <cite>Thompson2012</cite>
|-
| [[GH100]]
| none
| (α/α)6 core
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5gop 5gop]
| invertase
| ''Anabaena (Nostoc) sp.'' pcc7120
| sucrose
| '''Asp188'''
| Glu414
| <cite>Xie2016</cite>
|-
| [[GH102]]
| none
| double-ψ β-barrel
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}2pi8 2pi8]
| lytic transglycosylase A
| ''Escherichia coli''
| chitohexaose
| '''Asp308'''
| none
| <cite>van_Straaten2007</cite>
|-
| [[GH103]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1d0k 1d0k]
| lytic transglycosylase SLT35
| ''Escherichia coli''
| murodipeptides
| '''Glu162'''
| internal
| <cite>van_Asselt2000</cite>
|-
| [[GH106]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5mwk 5mwk]
| α-{{Smallcaps|l}}-rhamnosidase BT_0986
| ''Bacteroides thetaiotaomicron''
| pectin heptasaccharide
| '''Glu461'''
| Glu593 or Glu561
| <cite>Ndeh2017</cite>
|-
| [[GH107]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| ''predicted syn by clan''
| ''see at GH29''
|
|
|
|
|
|
|-
| [[GH113]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4cd8 4cd8]
| β-mannanase
| ''Alicyclobacillus acidocaldarius''
| mannobioimidazole
| '''Glu151'''
| Glu231
| <cite>Williams2014</cite>
|-
| [[GH116]]
| O
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at GH52''
|
|
|
|
|
|
|-
| [[GH117]]
| none
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}4ak7 4ak7]
| α-1,3-3,6-anhydro-{{Smallcaps|l}}-galactosidase
| ''Bacteroides plebeius''
| neoagarobiose
| '''His302'''
| Asp90
| <cite>Hehemann_2_2012</cite>
|-
| [[GH120]]
| none
| parallel β-helix and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3vsv 3vsv]
| β-xylosidase XylC
| ''Thermoanaerobacterium saccharolyticum'' JW/SL-YS485
| {{Smallcaps|d}}-xylose
| '''Glu405'''
| Asp382
| <cite>Huang2012</cite>
|-
| [[GH123]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5fr0 5fr0]
| exo-β-N-acetyl-galactosaminidase
| ''Clostridium perfringens''
| ''N''-difluoroacetyl-{{Smallcaps|d}}-galactosamine
| '''Glu345'''
| internal
| <cite>Noach2016</cite>
|-
| [[GH125]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5m7y 5m7y]
| exo-α-1,6-mannosidase
| ''Clostridium perfringens''
| 1,6-α-mannotriose
| '''Asp220'''
| Glu393
| <cite>Alonso-Gil2016</cite>
|-
| [[GH127]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3wrg 3wrg]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bifidobacterium longum''
| {{Smallcaps|l}}-arabinose
| '''Glu322'''
| Cys417
| <cite>Huang2014</cite>
|-
| [[GH128]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH1''
|
|
|
|
|
|
|-
| [[GH130]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5b0s 5b0s]
| β-1,2-mannobiose phosphorylase
| ''Listeria innocua''
| β-1,2-mannotriose
| '''Asp141''' relay
| phosphate
| <cite>Tsuda2015</cite>
|-
| [[GH134]]
| none
| β + α
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5jug 5jug]
| β-mannanase
| ''Streptomyces sp.''
| mannopentaose
| '''Glu45'''
| Asp57
| <cite>Jin2016</cite>
|-
| [[GH136]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}5gqf 5gqf]
| lacto-N-biosidase
| ''Bifidobacterium longum''
| lacto-N-biose
| '''Asp411'''
| Asp418
| <cite>Yamada2017</cite>
|-
| [[GH137]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|l}}
| unknown
| '''''anti'''''
| [{{PDBlink}}5mui 5mui]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0996
| ''Bacteroides thetaiotaomicron''
| pectin oligosaccharide
| '''Glu240'''
| Glu159
| <cite>Ndeh2017</cite>

|-
| [[GH138]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}6hzg 6hzg]
| α-1,2-{{Smallcaps|d}}-galacturonidase
| ''Bacteroides paurosaccharolyticus''
| alpha-{{Smallcaps|d}}-galactopyranuronic
| '''Glu294'''
| Glu361
| <cite>Labourel2019</cite>
|-
| [[GH146]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5opj 5opj]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0349
| ''Bacteroides thetaiotaomicron''
| {{Smallcaps|l}}-arabinose
| '''Glu320'''
| Cys416
| <cite>Luis2018</cite>
|-
| [[GH147]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH148]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH149]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH157]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH158]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH161]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [[GH162]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}6imw 5imw]
| endo-β-1,2-glucanase
| ''Talaromyces funiculosus''
| beta-1,2-glucan
| '''Glu262'''
| Asp446
| <cite>Tanaka2019</cite>
|-
| [http://www.cazy.org/GH0.html n.c.*]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2vjj 2vjj]
| endo-α-N-acetylglucosaminidase
| Bacteriophage HK620
| O18A1 O-antigen hexasaccharide
| '''Asp339'''
| Glu372
| <cite>Barbirz2008</cite>
|}
<nowiki>*</nowiki> n.c.: Found among the collection of [http://www.cazy.org/GH0.html non-classified GH sequences in the CAZy Database].

== References ==

<biblio>
# HeightmanVasella1999 Heightman TD and Vasella AT. ''Recent Insights into Inhibition, Structure, and Mechanism of Configuration-Retaining Glycosidases.'' Angew Chem Int Ed. 1999 38(6):750-770. [http://www3.interscience.wiley.com/journal/55000581/abstract Article online].
# Nerinckx2005 pmid=15642336
# Wu2012 pmid=23137336
# Perez1978 Pérez S and Marchessault RH. ''The exo-anomeric effect: experimental evidence from crystal structures.'' Carbohydr res. 1978 65:114-120. [http://dx.doi.org/10.1016/S0008-6215(00)84218-4 DOI:10.1016/S0008-6215(00)84218-4]
# Cramer1997 Cramer CJ, Truhlar DG, and French AD. ''Exo-anomeric effects on energies and geometries of different conformations of glucose and related systems in the gas phase and aqueous solution.'' Carbohydr res. 1997 298:1-14. [http://dx.doi.org/10.1016/S0008-6215(96)00297-2 DOI:10.1016/S0008-6215(96)00297-2]
# Johnson2009 pmid=19733839
# Alonso2016 pmid=26889578
# Gloster2006 pmid=17002288
# van_Bueren2009 pmid=18976664
# Hrmova2001 pmid=11709165
# Varrot2003 pmid=12595701
# Zhou1999 pmid=10508787
# Sulzenbacher1999 pmid=10200171
# Urbanikova2011 pmid=21501386
# Guerin2002 pmid=11884144
# Schubot2004 pmid=14756552
# Suzuki2009 pmid=19279191
# Wan2014 pmid=24419374
# Sandgren2004 pmid=15364577
# Uitdehaag1999 pmid=10331869
# Miyake2003 pmid=12741813
# Harris1993 pmid=8431441
# Allouch2004 pmid=15062085
# Papanikolau2001 pmid=11560481
# Prag2000 pmid=10884356
# Vocadlo2001 pmid=11518970
# Karlsen1996 pmid=15299731
# Baldwin1993 pmid=8259514
# Cartmell2008 pmid=18799462
# Fernandez-Leiro2010 pmid=20592022
# Abbott2007 pmid=17397864
# Sakurama2012 pmid=22451675
# Sim2008 pmid=18036614
# Verhaest2007 pmid=17335500
# Amaya2004 pmid=15130470
# Zhu2012 pmid=23015718
# Maksimainen2011 pmid=21130883
# Merceron2012 pmid=23012371
# Gibson2007 pmid=17455176
# Shah2008 pmid=18599462
# Czjzek2005 pmid=16212978
# Godoy2016 pmid=27685756
# Fujimoto2010 pmid=20739278
# Kitago2007 pmid=17905739
# Davies1996 pmid=15299721
# Lyu2014 pmid=24766439
# Karaveg2005 pmid=15713668
# Nerinckx2008 pmid=18619586
# Pluvinage2013 pmid=23921382
# Hoevel2003 pmid=14517232
# Espina2014 pmid=24816105
# Le_Nours2009 pmid=19089956
# Miyanaga2004 pmid=15292273
# Bianchetti2015 pmid=25752603
# Markovic-Housley2000 pmid=11080624
# Imamura2003 pmid=12618437
# Hill2013 pmid=24297913
# Miyazaki2016 pmid=27688023
# Touhara2014 pmid=24828502
# Suzuki2016 pmid=26494689
# Golan2004 pmid=14573597
# Meng2003 pmid=14517548
# Ito2011 pmid=21354427
# Hurtado-Gerrero2009 pmid=19097997
# Yaoi2007 pmid=17498741
# Thompson2015 pmid=25772148
# Barends2007 pmid=17420245
# Fujimoto2013 pmid=23486481
# Wu2015 pmid=26575439
# Pluvinage2017 pmid=28781080
# Dennis2006 pmid=16565725
# Abbott2009 pmid=19181667
# Hehemann_1_2012 pmid=23150581
# Ficko-Blean2008 pmid=18443291
# Zhu2009 pmid=20081828
# Sogabe2011 pmid=21543843
# Nam2015 pmid=26041776
# Nagae2007 pmid=17459873
# Kitamura2008 pmid=18981178
# Higgins2009 pmid=19608744
# van_Straaten2007 pmid=17502382
# van_Asselt2000 pmid=10684641
# Ndeh2017 pmid=28329766
# Labourel2019 pmid=30877196

# Luis2018 pmid=29255254
# Jin2016 Jin Y, Petricevic M, John A, Raich L, Jenkins H, Portela De Souza L, Cuskin F, Gilbert HJ, Rovira C, Goddard-Borger ED, Williams SJ, and Davies GJ. ''A β-Mannanase with a Lysozyme-like Fold and a Novel Molecular Catalytic Mechanism.'' ACS Cent Sci. 2016 Nov [http://dx.doi.org/10.1021/acscentsci.6b00232 DOI:10.1021/acscentsci.6b00232]
# Yamada2017 pmid=28392148
# Ohnuma2014 pmid=24582745
# Thompson2012 pmid=22219371
# Xie2016 pmid=27777307
# Williams2014 pmid=24339341
# Hehemann_2_2012 pmid=22393053
# Huang2012 pmid=22992047
# Noach2016 pmid=27038508
# Alonso-Gil2016 pmid=28026180
# Huang2014 Huang CH, Zhu Z, Cheng YS, Chan HC, Ko TP, Chen CC, Wang I, Ho MR, Hsu ST, Zeng YF, Huang YN, Liu JR, Guo RT. ''Structure and Catalytic Mechanism of a Glycoside Hydrolase Family-127 β-L-Arabinofuranosidase (HypBA1).'' J Bioprocess Biotech. 2014 4:171 [http://dx.doi.org/10.4172/2155-9821.1000171 DOI:10.4172/2155-9821.1000171]
# Tsuda2015 pmid=26632508
# Barbirz2008 pmid=18547389
# Tanaka2019 pmid=30926603

</biblio>

[[Category:Definitions and explanations]]

Syn/anti lateral protonation

2019-01-02T08:00:43Z

Wim Nerinckx: GH146 is anti

{{CuratorApproved}}
* [[Author]]: ^^^Wim Nerinckx^^^
* [[Responsible Curator]]: ^^^Spencer Williams^^^

----

== Overview ==

This page provides a table that summarizes the spatial positioning of the catalytic [[general acid]] residue in the active sites of [[glycoside hydrolase]]s, relative to the substrate. The table below updates those found in the seminal paper on this concept by Heightman and Vasella <cite>HeightmanVasella1999</cite>, and a following paper by Nerinckx ''et al.'' <cite>Nerinckx2005</cite>.

== Background ==

The ''"not from above, but from the side"'' concept of semi-lateral glycosidic oxygen [[General_acid/base|protonation]] by [[glycoside hydrolase]]s was introduced by Heightman and Vasella <cite>HeightmanVasella1999</cite>. It was originally only described for [[Anomeric centre (alpha and beta)|beta]]-equatorial [[glycoside hydrolase]]s, but appears to be equally applicable to enzymes acting on an [[Anomeric centre (alpha and beta)|alpha]]-axial glycosidic bond <cite>Nerinckx2005</cite>. When dividing [[Sub-site nomenclature|subsite -1]] into half-spaces by a plane defined by the glycosidic oxygen and C1' and H1' of the –1 glycoside, many ligand-complexed structures reveal that the [[General_acid/base|proton donor]] is positioned either in the ''syn'' half-space (near the ring-oxygen of the –1 glycoside), or in the ''anti'' half-space (on the opposite side of the ring-oxygen). Members of the same GH [[Families|family]] appear to share a common ''syn'' or ''anti'' [[General_acid/base|protonator]] arrangement and further, this specificity appears to be preserved within [[Clans|Clans]] of [[Families|families]]. This page's compilation of [[Sub-site nomenclature|subsite -1]] occupied complexes shows that about 70% of all GH [[Families|families]] are ''anti'' [[General_acid/base|protonators]].

Closer inspection of crystal structures of [[Sub-site nomenclature|–1/+1 subsite]]-spanning substrates, or substrate-analogue ligands, in complex with enzymes reveals a further intriguing corollary <cite>Nerinckx2005 Wu2012</cite>. In substrate-bound complexes with ''anti'' [[General_acid/base|protonating]] GH enzymes, the scissile [[Anomeric centre (alpha and beta)|anomeric bond]] (often studied using the thio-analogue) shows a dihedral angle φ (O5'-C1'-[O,S]x-Cx) that is in the lowest-energy synclinal (gauche) conformation. The rationale for this is that a minus synclinal dihedral angle φ for an equatorial glycosidic bond, or plus synclinal for an axial glycosidic bond <cite>Perez1978</cite>, allows for hyperconjugative overlap of the C1'-O5' antibonding orbital with an antiperiplanar-oriented lone pair orbital lobe of the glycosidic oxygen, thereby creating partial double bond character and stabilization of the glycosidic bond by 4–5 kcal/mol; this ground-state stabilizing phenomenon is known as the ‘exo-anomeric effect’ <cite>Cramer1997 Johnson2009 Alonso2016</cite>. ''Anti'' [[General_acid/base|protonation]] occurs on the glycosidic oxygen’s antiperiplanar lone pair, thereby removing the stabilizing exo-anomeric effect. This suggests that ''anti'' [[General_acid/base|protonation]] is an enzymic approach for lowering the activation barrier leading to the [[Transition state|transition state]] (Figure 1 centre).

''Syn'' [[General_acid/base|protonating]] [[glycoside hydrolase]]s apparently make use of a different approach <cite>Nerinckx2005 Wu2012</cite>. In many [[Sub-site nomenclature|–1/+1 subsite]]-spanning ligand complexes, the dihedral angle φ of the scissile anomeric bond has been rotated away from its lowest-energy synclinal position: clockwise to minus-anticlinal or antiperiplanar for beta-equatorial; counterclockwise to plus-anticlinal or antiperiplanar for alpha-axial [[Anomeric centre (alpha and beta)|anomeric bonds]]. This removes the hyperconjugative overlap and thus also the stabilizing exo-anomeric effect. And because of this rotation, a lone pair of the glycosidic oxygen is directed into the ''syn'' half-space, allowing it to be protonated by the ''syn''-positioned [[General_acid/base|proton donor]] (Figure 1 right).

[[File:Syn_anti.jpg|800px|thumb|center|Figure 1. Newman projections, with the glycosidic oxygen as proximal atom and the anomeric carbon as distal atom, showing ''anti'' (centre) versus ''syn'' (right) semi-lateral [[General_acid/base|protonation]] in beta-equatorial (top) and alpha-axial (bottom) [[glycoside hydrolase]]s. The indicated φ is the dihedral angle for O5'-C1'-O4-C4.]]

== Table of ''syn/anti'' protonation examples ==

This table contains only one example per GH [[Families|family]] of a ligand-complexed protein structure where the ''syn'' or ''anti'' positioning of the [[General_acid/base|proton donor]] can be clearly observed; other examples may be available on a [[Families|family-by-family]] basis. The reader is thus advised to consult the [http://www.cazy.org/fam/acc_GH.html#table CAZy database] for a current, comprehensive list of CAZyme structures. Where available, the selected examples are Michaelis-type complexes with the ligand spanning the [[Sub-site nomenclature|-1/+1 subsites]], since these have an intact glycosidic or thioglycosidic bond, or are ''N''-analogs of the substrate (''e.g.'' acarbose). In some examples, the [[General_acid/base|proton donor]] has been mutated (''e.g.'', to the corresponding amide or to an alanine), and in those cases one may wish to look at a superposition of the given PDB example with the structure of the native enzyme. If a Michaelis-type complex is not yet available, the second and third example choices, respectively, are trapped glycosyl-enzyme [[intermediate]]s and product complexes where [[Sub-site nomenclature|subsite -1]] is occupied.

''Please also be aware that this is a large table with many data. Please contact the page Author or Responsible Curator with corrections.''

=== Table ===
This table can be re-sorted by clicking on the icons in the header (''javascript must be turned on in your browser''). To reset the page to be sorted by GH family, click the ''View'' tab at the very top of the page.

{| {{Prettytable}} class="sortable"
|- valign="top"
! '''Family'''
! '''Clan'''
! '''Structure fold '''
! '''Anomeric specificity'''
! '''Mechanism'''
! '''''Syn/anti'' protonator'''
! '''Example PDB ID'''
! '''Enzyme'''
! '''Organism'''
! '''Ligand'''
! '''General acid'''
! '''Nucleophile or General base'''
! '''Reference'''
|-
| [[GH1]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2cer 2cer]
| β-glycosidase S
| ''Sulfolobus solfataricus'' P2
| phenethyl glucoimidazole
| '''Glu206'''
| Glu387
| <cite>Gloster2006</cite>
|-
| [[GH2]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vzu 2vzu]
| exo-β-glucosaminidase
| ''Amicolatopsis orientalis''
| PNP-β-{{Smallcaps|d}}-glucosamine
| '''Glu469'''
| Glu541
| <cite>van_Bueren2009</cite>
|-
| [[GH3]]
| none
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1iex 1iex]
| exo-1,3-1,4-glucanase
| ''Hordeum vulgare''
| thiocellobiose
| '''Glu491'''
| Asp285
| <cite>Hrmova2001</cite>
|-
| [[GH5]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1h2j 1h2j]
| endo-β-1,4-glucanase
| ''Bacillus agaradhaerens''
| 2',4'-DNP-2-F-cellobioside
| '''Glu129'''
| Glu228
| <cite>Varrot2003</cite>
|-
| [[GH6]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1qjw 1qjw]
| cellobiohydrolase 2
| ''Hypocrea jecorina''
| (Glc)2-S-(Glc)2
| '''Asp221'''
| debated
| <cite>Zhou1999</cite>
|-
| [[GH7]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1ovw 1ovw]
| endo-1,4-glucanase
| ''Fusarium oxysporum''
| thio-(Glc)5
| '''Glu202'''
| Glu197
| <cite>Sulzenbacher1999</cite>
|-
| [[GH8]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1kwf 1kwf]
| endo-1,4-glucanase
| ''Clostridium thermocellum''
| cellopentaose
| '''Glu95'''
| Asp278
| <cite>Guerin2002</cite>
|-
| [[GH9]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1rq5 1rq5]
| cellobiohydrolase
| ''Clostridium thermocellum''
| cellotetraose
| '''Glu795'''
| Asp383
| <cite>Schubot2004</cite>
|-
| [[GH10]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2d24 2d24]
| β-1,4-xylanase
| ''Streptomyces olivaceoviridis'' E-86
| xylopentaose
| '''Glu128'''
| Glu236
| <cite>Suzuki2009</cite>
|-
| [[GH11]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}4hk8 4hk8]
| endo-β-1,4-xylanase
| ''Hypocrea jecorina''
| xylohexaose
| '''Glu177'''
| Glu86
| <cite>Wan2014</cite>
|-
| [[GH12]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1w2u 1w2u]
| endoglucanase
| ''Humicola grisea''
| thiocellotetraose
| '''Glu205'''
| Glu120
| <cite>Sandgren2004</cite>
|-
| [[GH13]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1cxk 1cxk]
| β-cyclodextrin glucanotransferase
| ''Bacillus circulans''
| maltononaose
| '''Glu257'''
| Asp229
| <cite>Uitdehaag1999</cite>
|-
| [[GH14]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1itc 1itc]
| β-amylase
| ''Bacillus cereus''
| maltopentaose
| '''Glu172'''
| Glu367
| <cite>Miyake2003</cite>
|-
| [[GH15]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1dog 1dog]
| glucoamylase
| ''Aspergillus awamori''
| 1-deoxynojirimycin
| '''Glu179'''
| Glu400
| <cite>Harris1993</cite>
|-
| [[GH16]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1urx 1urx]
| β-agarase A
| ''Zobellia galactanivorans''
| oligoagarose
| '''Glu152'''
| Glu147
| <cite>Allouch2004</cite>
|-
| [[GH17]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH1''
|
|
|
|
|
|
|-
| [[GH18]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1ffr 1ffr]
| chitinase A
| ''Serratia marcescens''
| (NAG)6
| '''Glu315'''
| internal
| <cite>Papanikolau2001</cite>
|-
| [[GH19]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}3wh1 3wh1]
| chitinase
| ''Bryum coronatum''
| (GlcNAc)4
| '''Glu61'''
| Glu70
| <cite>Ohnuma2014</cite>
|-
| [[GH20]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1c7s 1c7s]
| chitobiase
| ''Serratia marcescens''
| chitobiose
| '''Glu540'''
| internal
| <cite>Prag2000</cite>
|-
| [[GH22]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1h6m 1h6m]
| lysozyme C
| ''Gallus gallus''
| Chit-2-F-chitosyl
| '''Glu35'''
| Asp52
| <cite>Vocadlo2001</cite>
|-
| [[GH23]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1lsp 1lsp]
| lysozyme G
| ''Cygnus atratus''
| Bulgecin A
| '''Glu73'''
| internal
| <cite>Karlsen1996</cite>
|-
| [[GH24]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}148l 148l]
| lysozyme E
| Bacteriophage T4
| chitobiosyl
| '''Glu11'''
| Glu26
| <cite>Baldwin1993</cite>
|-
| [[GH26]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vx6 2vx6]
| exo-β-mannanase
| ''Cellvibrio japonicus'' Ueda107
| Gal1Man4
| '''Glu221'''
| Glu338
| <cite>Cartmell2008</cite>
|-
| [[GH27]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}} / beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3lrm 3lrm]
| α-galactosidase
| ''Saccharomyces cerevisiae''
| raffinose
| '''Asp209'''
| Asp141
| <cite>Fernandez-Leiro2010</cite>
|-
| [[GH28]]
| N
| β-helix
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}2uvf 2uvf]
| exo-polygalacturonosidase
| ''Yersinia enterocolitica'' ATCC9610D
| digalacturonic acid
| '''Asp402'''
| Asp381 Asp403
| <cite>Abbott2007</cite>
|-
| [[GH29]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| '''''syn'''''
| [{{PDBlink}}3uet 3uet]
| α-1,3/4-fucosidase
| ''Bifidobacterium longum'' subsp. infantis
| lacto-''N''-fucopentaose II
| '''Glu217'''
| Asp172
| <cite>Sakurama2012</cite>
|-
| [[GH30]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2y24 2y24]
| glucurono-xylanase
| ''Dickea chrysanthemi'' D1
| glucuronoxylan tetrasaccharide
| '''Glu163'''
| Glu253
| <cite>Urbanikova2011</cite>
|-
| [[GH31]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2qmj 2qmj]
| maltase-glucoamylase
| ''Homo sapiens''
| acarbose
| '''Asp542'''
| Asp443
| <cite>Sim2008</cite>
|-
| [[GH32]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2add 2add]
| fructan β-(2,1)-fructosidase
| ''Cichorium intybus''
| sucrose
| '''Glu201'''
| Asp22
| <cite>Verhaest2007</cite>
|-
| [[GH33]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1s0i 1s0i]
| transsialidase
| ''Trypanosoma cruzi''
| sialyllactose
| '''Asp59'''
| Tyr342
| <cite>Amaya2004</cite>
|-
| [[GH34]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzw 4gzw]
| N2 neuraminidase
| ''Influenza'' A Tanzania/205/2010 H3N2
| α-{{Smallcaps|d}}-Neup5Ac-(2,3)-β-{{Smallcaps|d}}-Galp-(1,4)-β-{{Smallcaps|d}}-GlcpNAc
| '''Asp151'''
| Tyr406
| <cite>Zhu2012</cite>
|-
| [[GH35]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3ogv 3ogv]
| β-galactosidase
| ''Hypocrea jecorina''
| 2-phenylethyl 1-thio-β-{{Smallcaps|d}}-galactopyranoside
| '''Glu200'''
| Glu298
| <cite>Maksimainen2011</cite>
|-
| [[GH36]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4fns 4fns]
| β-galactosidase
| ''Geobacillus stearothermophilus''
| 1-deoxy galactonojirimycin
| '''Asp584'''
| Asp478
| <cite>Merceron2012</cite>
|-
| [[GH37]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2jf4 2jf4]
| trehalase
| ''Escherichia coli''
| validoxylamine
| '''Asp312'''
| Glu496
| <cite>Gibson2007</cite>
|-
| [[GH38]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3czn 3czn]
| Golgi α-mannosidase II
| ''Drosophila melanogaster''
| GlcNAcMan(5)GlcNAc(2)
| '''Asp341'''
| Asp204
| <cite>Shah2008</cite>
|-
| [[GH39]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2bfg 2bfg]
| β-xylosidase
| ''Geobacillus stearothermophilus''
| 2,5-dinitrophenyl-β-{{Smallcaps|d}}-xyloside
| '''Glu160'''
| Glu278
| <cite>Czjzek2005</cite>
|-
| [[GH42]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ucf 4ucf]
| β-galactosidase
| ''Bifidobacterium bifidum''
| {{Smallcaps|d}}-galactose
| '''Glu161'''
| Glu320
| <cite>Godoy2016</cite>
|-
| [[GH43]]
| F
| 5-fold β-propeller
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3akh 3akh]
| exo-1,5-α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces avermitilis''
| α-1,5-arabinofuranotriose
| '''Glu196'''
| Asp220
| <cite>Fujimoto2010</cite>
|-
| [[GH44]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2eqd 2eqd]
| endoglucanase
| ''Clostridium thermocellum''
| cellooctaose
| '''Glu186'''
| Glu359
| <cite>Kitago2007</cite>
|-
| [[GH45]]
| none
| 6-stranded β-barrel
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4eng 4eng]
| endo-1,4-glucanase
| ''Humicola insolens''
| cellohexaose
| '''Asp121'''
| Asp10
| <cite>Davies1996</cite>
|-
| [[GH46]]
| I
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4olt 4olt]
| chitosanase
| ''Microbacterium sp.'' OU01
| hexa-glucosamine
| '''Glu25'''
| Asp43
| <cite>Lyu2014</cite>
|-
| [[GH47]]
| none
| (α/α)7
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1x9d 1x9d]
| α-mannosidase I
| ''Homo sapiens''
| Me-2-S-(α-Man)-2-thio-α-Man
| '''Asp463'''
| Glu599
| <cite>Karaveg2005</cite>, <cite>Nerinckx2008</cite>
|-
| [[GH48]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH8''
|
|
|
|
|
|
|-
| [[GH49]]
| N
| β-helix
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH28''
|
|
|
|
|
|
|-
| [[GH50]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4bq5 4bq5]
| exo-β-agarase
| ''Saccharophagus degradans''
| neoagarotetraose
| '''Glu535'''
| Glu695
| <cite>Pluvinage2013</cite>
|-
| [[GH51]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1qw9 1qw9]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Geobacillus stearothermophilus''
| PNP-{{Smallcaps|l}}-arabinofuranoside
| '''Glu175'''
| Glu294
| <cite>Hoevel2003</cite>
|-
| [[GH52]]
| O
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4c1p 4c1p]
| β-xylosidase
| ''Geobacillus thermoglucosidasius''
| xylobiose
| '''Asp517'''
| Glu537
| <cite>Espina2014</cite>
|-
| [[GH53]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2ccr 2ccr]
| β-1,4-galactanase
| ''Bacillus licheniformis''
| galactotriose
| '''Glu165'''
| Glu263
| <cite>Le_Nours2009</cite>
|-
| [[GH54]]
| none
| β-sandwich
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1wd4 1wd4]
| α-{{Smallcaps|l}}-arabinofuranosidase B
| ''Aspergillus kawachii''
| {{Smallcaps|l}}-arabinofuranose
| '''Asp297'''
| Glu221
| <cite>Miyanaga2004</cite>
|-
| [[GH55]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4tz5 4tz5]
| exo-β-1,3-glucanase
| ''Streptomyces sp.'' SirexAA-E
| laminarihexaose
| '''Glu502'''
| unknown
| <cite>Bianchetti2015</cite>
|-
| [[GH56]]
| none
| (β/α)7
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1fcv 1fcv]
| hyaluronidase
| ''Apis mellifera''
| (hyaluron.)4
| '''Glu113'''
| internal
| <cite>Markovic-Housley2000</cite>
|-
| [[GH57]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1k1y 1k1y]
| glucanotransferase
| ''Thermococcus litoralis''
| acarbose
| '''Asp214'''
| Glu123
| <cite>Imamura2003</cite>
|-
| [[GH59]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ccc 4ccc]
| β-galactocerebrosidase
| ''Mus musculus''
| PNP-β-{{Smallcaps|d}}-galactoside
| '''Glu182'''
| Glu258
| <cite>Hill2013</cite>
|-
| [[GH62]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| ''predicted anti by clan''
| ''see at GH43''
|
|
|
|
|
|
|-
| [[GH63]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5ca3 5ca3]
| α-glucosidase
| ''Escherichia coli''
| glucose and lactose
| '''Asp501'''
| Glu727
| <cite>Miyazaki2016</cite>
|-
| [[GH65]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}4ktr 4ktr]
| 2-O-α-glucosylglycerol phosphorylase
| ''Bacillus selenitireducens''
| isofagomine
| '''Glu475'''
| phosphate
| <cite>Touhara2014</cite>
|-
| [[GH66]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5axh 5axh]
| dextranase
| ''Thermoanaerobacter pseudethanolicus''
| isomaltohexaose
| '''Glu374'''
| Asp312
| <cite>Suzuki2016</cite>
|-
| [[GH67]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1l8n 1l8n]
| α-glucuronidase
| ''Geobacillus stearothermophilus''
| 4-O-methyl-{{Smallcaps|d}}-glucuronic acid and xylotriose
| '''Glu286'''
| Asp364 Glu392
| <cite>Golan2004</cite>
|-
| [[GH68]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1pt2 1pt2]
| levansucrase
| ''Bacillus subtilis''
| sucrose
| '''Glu342'''
| Asp86
| <cite>Meng2003</cite>
|-
| [[GH70]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3aic 3aic]
| glucansucrase
| ''Streptococcus mutans''
| α-acarbose
| '''Glu515'''
| Asp477
| <cite>Ito2011</cite>
|-
| [[GH72]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w62 2w62]
| β-1,3-glucanotransferase
| ''Saccharomyces cerevisiae'' S288C
| laminaripentaose
| '''Glu176'''
| Glu275
| <cite>Hurtado-Gerrero2009</cite>
|-
| [[GH74]]
| none
| 7-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}2ebs 2ebs]
| cellobiohydrolase (OXG-RCBH)
| ''Geotrichum sp.'' m128
| xyloglucan heptasaccharide
| '''Asp465'''
| Asp35
| <cite>Yaoi2007</cite>
|-
| [[GH76]]
| none
| (α/α)6
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5agd 5agd]
| endo-α-1,6-mannanase
| ''Bacillus circulans''
| α-1,6-mannopentaose
| '''Asp125'''
| Asp124
| <cite>Thompson2015</cite>
|-
| [[GH77]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2oww 2oww]
| 4-α-glucanotransferase
| ''Thermus thermofilus''
| acarbose + 4-deoxy-α-{{Smallcaps|d}}-glucose
| '''Glu340'''
| Asp293
| <cite>Barends2007</cite>
|-
| [[GH78]]
| H
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3w5n 3w5n]
| α-{{Smallcaps|l}}-rhamnosidase
| ''Streptomyces avermitilis''
| {{Smallcaps|l}}-rhamnose
| '''Glu636'''
| Glu895
| <cite>Fujimoto2013</cite>
|-
| [[GH79]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5e9c 5e9c]
| heparanase
| ''Homo sapiens''
| heparin tetrasaccharide
| '''Glu225'''
| Glu343
| <cite>Wu2015</cite>
|-
| [[GH80]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH24''
|
|
|
|
|
|
|-
| [[GH81]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5t4g 5t4g]
| endo-β-1,3-glucanase
| ''Bacillus halodurans'' C-125
| laminarin
| '''Asp466'''
| Glu542
| <cite>Pluvinage2017</cite>
|-
| [[GH83]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH33''
|
|
|
|
|
|
|-
| [[GH84]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2chn 2chn]
| β-''N''-acetyl-glucosaminidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| NAG-thiazoline
| '''Glu242'''
| internal
| <cite>Dennis2006</cite>
|-
| [[GH85]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w92 2w92]
| endo-β-''N''-acetyl-glucosaminidase D
| ''Streptococcus pneumoniae'' TIGR4
| NAG-thiazoline
| '''Glu337'''
| internal
| <cite>Abbott2009</cite>
|-
| [[GH86]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4aw7 4aw7]
| β-porphyranase
| ''Bacteroides plebeius''
| porphyran fragment
| '''Glu152'''
| Glu279
| <cite>Hehemann_1_2012</cite>
|-
| [[GH89]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vcb 2vcb]
| α-''N''-acetyl-glucosaminidase
| ''Clostridium perfringens''
| PUGNAc
| '''Glu483'''
| Glu601
| <cite>Ficko-Blean2008</cite>
|-
| [[GH92]]
| none
| (α/α)6 and β-sandwich
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ww1 2ww1]
| α-1,2-mannosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| thiomannobioside
| '''Glu533'''
| Asp644 Asp642
| <cite>Zhu2009</cite>
|-
| [[GH93]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3a72 3a72]
| exo-arabinanase
| ''Penicillium chrysogenum''
| arabinobiose
| '''Glu246'''
| Glu174
| <cite>Sogabe2011</cite>
|-
| [[GH94]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4zli 4zli]
| cellobionic acid phosphorylase
| ''Saccharophagus degradans''
| 3-O-β-{{Smallcaps|d}}-glucopyranosyl-α-{{Smallcaps|d}}-glucopyranuronic acid
| '''Asp472'''
| phosphate
| <cite>Nam2015</cite>
|-
| [[GH95]]
| none
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ead 2ead]
| α-1,2-{{Smallcaps|l}}-fucosidase
| ''Bifidobacterium bifidum''
| Fuc-α-1,2-Gal
| '''Glu566'''
| Asn423 Asp766
| <cite>Nagae2007</cite>
|-
| [[GH97]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining + inverting
| '''''anti'''''
| [{{PDBlink}}2zq0 2zq0]
| α-glucosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| acarbose
| '''Glu532'''
| Glu508
| <cite>Kitamura2008</cite>
|-
| [[GH98]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2wmg 2wmg]
| endo-β-1,4-galactosidase
| ''Streptococcus pneumoniae''
| A-LewisY pentasaccharide
| '''Glu158'''
| Asp251 Glu301
| <cite>Higgins2009</cite>
|-
| [[GH99]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ad4 4ad4]
| endo-α-mannosidase
| ''Bacteroides xylanisolvens''
| glucose-1,3-isofagomine and α-1,2- mannobiose
| '''Glu336'''
| debated
| <cite>Thompson2012</cite>
|-
| [[GH100]]
| none
| (α/α)6 core
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5gop 5gop]
| invertase
| ''Anabaena (Nostoc) sp.'' pcc7120
| sucrose
| '''Asp188'''
| Glu414
| <cite>Xie2016</cite>
|-
| [[GH102]]
| none
| double-ψ β-barrel
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}2pi8 2pi8]
| lytic transglycosylase A
| ''Escherichia coli''
| chitohexaose
| '''Asp308'''
| none
| <cite>van_Straaten2007</cite>
|-
| [[GH103]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1d0k 1d0k]
| lytic transglycosylase SLT35
| ''Escherichia coli''
| murodipeptides
| '''Glu162'''
| internal
| <cite>van_Asselt2000</cite>
|-
| [[GH106]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5mwk 5mwk]
| α-{{Smallcaps|l}}-rhamnosidase BT_0986
| ''Bacteroides thetaiotaomicron''
| pectin heptasaccharide
| '''Glu461'''
| Glu593 or Glu561
| <cite>Ndeh2017</cite>
|-
| [[GH107]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| ''predicted syn by clan''
| ''see at GH29''
|
|
|
|
|
|
|-
| [[GH113]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4cd8 4cd8]
| β-mannanase
| ''Alicyclobacillus acidocaldarius''
| mannobioimidazole
| '''Glu151'''
| Glu231
| <cite>Williams2014</cite>
|-
| [[GH116]]
| O
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at GH52''
|
|
|
|
|
|
|-
| [[GH117]]
| none
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}4ak7 4ak7]
| α-1,3-3,6-anhydro-{{Smallcaps|l}}-galactosidase
| ''Bacteroides plebeius''
| neoagarobiose
| '''His302'''
| Asp90
| <cite>Hehemann_2_2012</cite>
|-
| [[GH120]]
| none
| parallel β-helix and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3vsv 3vsv]
| β-xylosidase XylC
| ''Thermoanaerobacterium saccharolyticum'' JW/SL-YS485
| {{Smallcaps|d}}-xylose
| '''Glu405'''
| Asp382
| <cite>Huang2012</cite>
|-
| [[GH123]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5fr0 5fr0]
| exo-β-N-acetyl-galactosaminidase
| ''Clostridium perfringens''
| ''N''-difluoroacetyl-{{Smallcaps|d}}-galactosamine
| '''Glu345'''
| internal
| <cite>Noach2016</cite>
|-
| [[GH125]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5m7y 5m7y]
| exo-α-1,6-mannosidase
| ''Clostridium perfringens''
| 1,6-α-mannotriose
| '''Asp220'''
| Glu393
| <cite>Alonso-Gil2016</cite>
|-
| [[GH127]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3wrg 3wrg]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bifidobacterium longum''
| {{Smallcaps|l}}-arabinose
| '''Glu322'''
| Cys417
| <cite>Huang2014</cite>
|-
| [[GH128]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH1''
|
|
|
|
|
|
|-
| [[GH130]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5b0s 5b0s]
| β-1,2-mannobiose phosphorylase
| ''Listeria innocua''
| β-1,2-mannotriose
| '''Asp141''' relay
| phosphate
| <cite>Tsuda2015</cite>
|-
| [[GH134]]
| none
| β + α
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5jug 5jug]
| β-mannanase
| ''Streptomyces sp.''
| mannopentaose
| '''Glu45'''
| Asp57
| <cite>Jin2016</cite>
|-
| [[GH136]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}5gqf 5gqf]
| lacto-N-biosidase
| ''Bifidobacterium longum''
| lacto-N-biose
| '''Asp411'''
| Asp418
| <cite>Yamada2017</cite>
|-
| [[GH137]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|l}}
| unknown
| '''''anti'''''
| [{{PDBlink}}5mui 5mui]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0996
| ''Bacteroides thetaiotaomicron''
| pectin oligosaccharide
| '''Glu240'''
| Glu159
| <cite>Ndeh2017</cite>
|-
| [[GH146]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5opj 5opj]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0349
| ''Bacteroides thetaiotaomicron''

| {{Smallcaps|l}}-arabinose

| '''Glu320'''
| Cys416
| <cite>Luis2018</cite>
|-
| [[GH147]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH148]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH149]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [http://www.cazy.org/GH0.html n.c.*]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2vjj 2vjj]
| endo-α-N-acetylglucosaminidase
| Bacteriophage HK620
| O18A1 O-antigen hexasaccharide
| '''Asp339'''
| Glu372
| <cite>Barbirz2008</cite>
|}
<nowiki>*</nowiki> n.c.: Found among the collection of [http://www.cazy.org/GH0.html non-classified GH sequences in the CAZy Database].

== References ==

<biblio>
# HeightmanVasella1999 Heightman TD and Vasella AT. ''Recent Insights into Inhibition, Structure, and Mechanism of Configuration-Retaining Glycosidases.'' Angew Chem Int Ed. 1999 38(6):750-770. [http://www3.interscience.wiley.com/journal/55000581/abstract Article online].
# Nerinckx2005 pmid=15642336
# Wu2012 pmid=23137336
# Perez1978 Pérez S and Marchessault RH. ''The exo-anomeric effect: experimental evidence from crystal structures.'' Carbohydr res. 1978 65:114-120. [http://dx.doi.org/10.1016/S0008-6215(00)84218-4 DOI:10.1016/S0008-6215(00)84218-4]
# Cramer1997 Cramer CJ, Truhlar DG, and French AD. ''Exo-anomeric effects on energies and geometries of different conformations of glucose and related systems in the gas phase and aqueous solution.'' Carbohydr res. 1997 298:1-14. [http://dx.doi.org/10.1016/S0008-6215(96)00297-2 DOI:10.1016/S0008-6215(96)00297-2]
# Johnson2009 pmid=19733839
# Alonso2016 pmid=26889578
# Gloster2006 pmid=17002288
# van_Bueren2009 pmid=18976664
# Hrmova2001 pmid=11709165
# Varrot2003 pmid=12595701
# Zhou1999 pmid=10508787
# Sulzenbacher1999 pmid=10200171
# Urbanikova2011 pmid=21501386
# Guerin2002 pmid=11884144
# Schubot2004 pmid=14756552
# Suzuki2009 pmid=19279191
# Wan2014 pmid=24419374
# Sandgren2004 pmid=15364577
# Uitdehaag1999 pmid=10331869
# Miyake2003 pmid=12741813
# Harris1993 pmid=8431441
# Allouch2004 pmid=15062085
# Papanikolau2001 pmid=11560481
# Prag2000 pmid=10884356
# Vocadlo2001 pmid=11518970
# Karlsen1996 pmid=15299731
# Baldwin1993 pmid=8259514
# Cartmell2008 pmid=18799462
# Fernandez-Leiro2010 pmid=20592022
# Abbott2007 pmid=17397864
# Sakurama2012 pmid=22451675
# Sim2008 pmid=18036614
# Verhaest2007 pmid=17335500
# Amaya2004 pmid=15130470
# Zhu2012 pmid=23015718
# Maksimainen2011 pmid=21130883
# Merceron2012 pmid=23012371
# Gibson2007 pmid=17455176
# Shah2008 pmid=18599462
# Czjzek2005 pmid=16212978
# Godoy2016 pmid=27685756
# Fujimoto2010 pmid=20739278
# Kitago2007 pmid=17905739
# Davies1996 pmid=15299721
# Lyu2014 pmid=24766439
# Karaveg2005 pmid=15713668
# Nerinckx2008 pmid=18619586
# Pluvinage2013 pmid=23921382
# Hoevel2003 pmid=14517232
# Espina2014 pmid=24816105
# Le_Nours2009 pmid=19089956
# Miyanaga2004 pmid=15292273
# Bianchetti2015 pmid=25752603
# Markovic-Housley2000 pmid=11080624
# Imamura2003 pmid=12618437
# Hill2013 pmid=24297913
# Miyazaki2016 pmid=27688023
# Touhara2014 pmid=24828502
# Suzuki2016 pmid=26494689
# Golan2004 pmid=14573597
# Meng2003 pmid=14517548
# Ito2011 pmid=21354427
# Hurtado-Gerrero2009 pmid=19097997
# Yaoi2007 pmid=17498741
# Thompson2015 pmid=25772148
# Barends2007 pmid=17420245
# Fujimoto2013 pmid=23486481
# Wu2015 pmid=26575439
# Pluvinage2017 pmid=28781080
# Dennis2006 pmid=16565725
# Abbott2009 pmid=19181667
# Hehemann_1_2012 pmid=23150581
# Ficko-Blean2008 pmid=18443291
# Zhu2009 pmid=20081828
# Sogabe2011 pmid=21543843
# Nam2015 pmid=26041776
# Nagae2007 pmid=17459873
# Kitamura2008 pmid=18981178
# Higgins2009 pmid=19608744
# van_Straaten2007 pmid=17502382
# van_Asselt2000 pmid=10684641
# Ndeh2017 pmid=28329766
# Luis2018 pmid=29255254
# Jin2016 Jin Y, Petricevic M, John A, Raich L, Jenkins H, Portela De Souza L, Cuskin F, Gilbert HJ, Rovira C, Goddard-Borger ED, Williams SJ, and Davies GJ. ''A β-Mannanase with a Lysozyme-like Fold and a Novel Molecular Catalytic Mechanism.'' ACS Cent Sci. 2016 Nov [http://dx.doi.org/10.1021/acscentsci.6b00232 DOI:10.1021/acscentsci.6b00232]
# Yamada2017 pmid=28392148
# Ohnuma2014 pmid=24582745
# Thompson2012 pmid=22219371
# Xie2016 pmid=27777307
# Williams2014 pmid=24339341
# Hehemann_2_2012 pmid=22393053
# Huang2012 pmid=22992047
# Noach2016 pmid=27038508
# Alonso-Gil2016 pmid=28026180
# Huang2014 Huang CH, Zhu Z, Cheng YS, Chan HC, Ko TP, Chen CC, Wang I, Ho MR, Hsu ST, Zeng YF, Huang YN, Liu JR, Guo RT. ''Structure and Catalytic Mechanism of a Glycoside Hydrolase Family-127 β-L-Arabinofuranosidase (HypBA1).'' J Bioprocess Biotech. 2014 4:171 [http://dx.doi.org/10.4172/2155-9821.1000171 DOI:10.4172/2155-9821.1000171]
# Tsuda2015 pmid=26632508
# Barbirz2008 pmid=18547389

</biblio>

[[Category:Definitions and explanations]]

Syn/anti lateral protonation

2018-10-20T08:55:24Z

Wim Nerinckx: gh136 is syn

{{CuratorApproved}}
* [[Author]]: ^^^Wim Nerinckx^^^
* [[Responsible Curator]]: ^^^Spencer Williams^^^

----

== Overview ==

This page provides a table that summarizes the spatial positioning of the catalytic [[general acid]] residue in the active sites of [[glycoside hydrolase]]s, relative to the substrate. The table below updates those found in the seminal paper on this concept by Heightman and Vasella <cite>HeightmanVasella1999</cite>, and a following paper by Nerinckx ''et al.'' <cite>Nerinckx2005</cite>.

== Background ==

The ''"not from above, but from the side"'' concept of semi-lateral glycosidic oxygen [[General_acid/base|protonation]] by [[glycoside hydrolase]]s was introduced by Heightman and Vasella <cite>HeightmanVasella1999</cite>. It was originally only described for [[Anomeric centre (alpha and beta)|beta]]-equatorial [[glycoside hydrolase]]s, but appears to be equally applicable to enzymes acting on an [[Anomeric centre (alpha and beta)|alpha]]-axial glycosidic bond <cite>Nerinckx2005</cite>. When dividing [[Sub-site nomenclature|subsite -1]] into half-spaces by a plane defined by the glycosidic oxygen and C1' and H1' of the –1 glycoside, many ligand-complexed structures reveal that the [[General_acid/base|proton donor]] is positioned either in the ''syn'' half-space (near the ring-oxygen of the –1 glycoside), or in the ''anti'' half-space (on the opposite side of the ring-oxygen). Members of the same GH [[Families|family]] appear to share a common ''syn'' or ''anti'' [[General_acid/base|protonator]] arrangement and further, this specificity appears to be preserved within [[Clans|Clans]] of [[Families|families]]. This page's compilation of [[Sub-site nomenclature|subsite -1]] occupied complexes shows that about 70% of all GH [[Families|families]] are ''anti'' [[General_acid/base|protonators]].

Closer inspection of crystal structures of [[Sub-site nomenclature|–1/+1 subsite]]-spanning substrates, or substrate-analogue ligands, in complex with enzymes reveals a further intriguing corollary <cite>Nerinckx2005 Wu2012</cite>. In substrate-bound complexes with ''anti'' [[General_acid/base|protonating]] GH enzymes, the scissile [[Anomeric centre (alpha and beta)|anomeric bond]] (often studied using the thio-analogue) shows a dihedral angle φ (O5'-C1'-[O,S]x-Cx) that is in the lowest-energy synclinal (gauche) conformation. The rationale for this is that a minus synclinal dihedral angle φ for an equatorial glycosidic bond, or plus synclinal for an axial glycosidic bond <cite>Perez1978</cite>, allows for hyperconjugative overlap of the C1'-O5' antibonding orbital with an antiperiplanar-oriented lone pair orbital lobe of the glycosidic oxygen, thereby creating partial double bond character and stabilization of the glycosidic bond by 4–5 kcal/mol; this ground-state stabilizing phenomenon is known as the ‘exo-anomeric effect’ <cite>Cramer1997 Johnson2009 Alonso2016</cite>. ''Anti'' [[General_acid/base|protonation]] occurs on the glycosidic oxygen’s antiperiplanar lone pair, thereby removing the stabilizing exo-anomeric effect. This suggests that ''anti'' [[General_acid/base|protonation]] is an enzymic approach for lowering the activation barrier leading to the [[Transition state|transition state]] (Figure 1 centre).

''Syn'' [[General_acid/base|protonating]] [[glycoside hydrolase]]s apparently make use of a different approach <cite>Nerinckx2005 Wu2012</cite>. In many [[Sub-site nomenclature|–1/+1 subsite]]-spanning ligand complexes, the dihedral angle φ of the scissile anomeric bond has been rotated away from its lowest-energy synclinal position: clockwise to minus-anticlinal or antiperiplanar for beta-equatorial; counterclockwise to plus-anticlinal or antiperiplanar for alpha-axial [[Anomeric centre (alpha and beta)|anomeric bonds]]. This removes the hyperconjugative overlap and thus also the stabilizing exo-anomeric effect. And because of this rotation, a lone pair of the glycosidic oxygen is directed into the ''syn'' half-space, allowing it to be protonated by the ''syn''-positioned [[General_acid/base|proton donor]] (Figure 1 right).

[[File:Syn_anti.jpg|800px|thumb|center|Figure 1. Newman projections, with the glycosidic oxygen as proximal atom and the anomeric carbon as distal atom, showing ''anti'' (centre) versus ''syn'' (right) semi-lateral [[General_acid/base|protonation]] in beta-equatorial (top) and alpha-axial (bottom) [[glycoside hydrolase]]s. The indicated φ is the dihedral angle for O5'-C1'-O4-C4.]]

== Table of ''syn/anti'' protonation examples ==

This table contains only one example per GH [[Families|family]] of a ligand-complexed protein structure where the ''syn'' or ''anti'' positioning of the [[General_acid/base|proton donor]] can be clearly observed; other examples may be available on a [[Families|family-by-family]] basis. The reader is thus advised to consult the [http://www.cazy.org/fam/acc_GH.html#table CAZy database] for a current, comprehensive list of CAZyme structures. Where available, the selected examples are Michaelis-type complexes with the ligand spanning the [[Sub-site nomenclature|-1/+1 subsites]], since these have an intact glycosidic or thioglycosidic bond, or are ''N''-analogs of the substrate (''e.g.'' acarbose). In some examples, the [[General_acid/base|proton donor]] has been mutated (''e.g.'', to the corresponding amide or to an alanine), and in those cases one may wish to look at a superposition of the given PDB example with the structure of the native enzyme. If a Michaelis-type complex is not yet available, the second and third example choices, respectively, are trapped glycosyl-enzyme [[intermediate]]s and product complexes where [[Sub-site nomenclature|subsite -1]] is occupied.

''Please also be aware that this is a large table with many data. Please contact the page Author or Responsible Curator with corrections.''

=== Table ===
This table can be re-sorted by clicking on the icons in the header (''javascript must be turned on in your browser''). To reset the page to be sorted by GH family, click the ''View'' tab at the very top of the page.

{| {{Prettytable}} class="sortable"
|- valign="top"
! '''Family'''
! '''Clan'''
! '''Structure fold '''
! '''Anomeric specificity'''
! '''Mechanism'''
! '''''Syn/anti'' protonator'''
! '''Example PDB ID'''
! '''Enzyme'''
! '''Organism'''
! '''Ligand'''
! '''General acid'''
! '''Nucleophile or General base'''
! '''Reference'''
|-
| [[GH1]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2cer 2cer]
| β-glycosidase S
| ''Sulfolobus solfataricus'' P2
| phenethyl glucoimidazole
| '''Glu206'''
| Glu387
| <cite>Gloster2006</cite>
|-
| [[GH2]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vzu 2vzu]
| exo-β-glucosaminidase
| ''Amicolatopsis orientalis''
| PNP-β-{{Smallcaps|d}}-glucosamine
| '''Glu469'''
| Glu541
| <cite>van_Bueren2009</cite>
|-
| [[GH3]]
| none
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1iex 1iex]
| exo-1,3-1,4-glucanase
| ''Hordeum vulgare''
| thiocellobiose
| '''Glu491'''
| Asp285
| <cite>Hrmova2001</cite>
|-
| [[GH5]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1h2j 1h2j]
| endo-β-1,4-glucanase
| ''Bacillus agaradhaerens''
| 2',4'-DNP-2-F-cellobioside
| '''Glu129'''
| Glu228
| <cite>Varrot2003</cite>
|-
| [[GH6]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1qjw 1qjw]
| cellobiohydrolase 2
| ''Hypocrea jecorina''
| (Glc)2-S-(Glc)2
| '''Asp221'''
| debated
| <cite>Zhou1999</cite>
|-
| [[GH7]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1ovw 1ovw]
| endo-1,4-glucanase
| ''Fusarium oxysporum''
| thio-(Glc)5
| '''Glu202'''
| Glu197
| <cite>Sulzenbacher1999</cite>
|-
| [[GH8]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1kwf 1kwf]
| endo-1,4-glucanase
| ''Clostridium thermocellum''
| cellopentaose
| '''Glu95'''
| Asp278
| <cite>Guerin2002</cite>
|-
| [[GH9]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1rq5 1rq5]
| cellobiohydrolase
| ''Clostridium thermocellum''
| cellotetraose
| '''Glu795'''
| Asp383
| <cite>Schubot2004</cite>
|-
| [[GH10]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2d24 2d24]
| β-1,4-xylanase
| ''Streptomyces olivaceoviridis'' E-86
| xylopentaose
| '''Glu128'''
| Glu236
| <cite>Suzuki2009</cite>
|-
| [[GH11]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}4hk8 4hk8]
| endo-β-1,4-xylanase
| ''Hypocrea jecorina''
| xylohexaose
| '''Glu177'''
| Glu86
| <cite>Wan2014</cite>
|-
| [[GH12]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1w2u 1w2u]
| endoglucanase
| ''Humicola grisea''
| thiocellotetraose
| '''Glu205'''
| Glu120
| <cite>Sandgren2004</cite>
|-
| [[GH13]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1cxk 1cxk]
| β-cyclodextrin glucanotransferase
| ''Bacillus circulans''
| maltononaose
| '''Glu257'''
| Asp229
| <cite>Uitdehaag1999</cite>
|-
| [[GH14]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1itc 1itc]
| β-amylase
| ''Bacillus cereus''
| maltopentaose
| '''Glu172'''
| Glu367
| <cite>Miyake2003</cite>
|-
| [[GH15]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1dog 1dog]
| glucoamylase
| ''Aspergillus awamori''
| 1-deoxynojirimycin
| '''Glu179'''
| Glu400
| <cite>Harris1993</cite>
|-
| [[GH16]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1urx 1urx]
| β-agarase A
| ''Zobellia galactanivorans''
| oligoagarose
| '''Glu152'''
| Glu147
| <cite>Allouch2004</cite>
|-
| [[GH17]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH1''
|
|
|
|
|
|
|-
| [[GH18]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1ffr 1ffr]
| chitinase A
| ''Serratia marcescens''
| (NAG)6
| '''Glu315'''
| internal
| <cite>Papanikolau2001</cite>
|-
| [[GH19]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}3wh1 3wh1]
| chitinase
| ''Bryum coronatum''
| (GlcNAc)4
| '''Glu61'''
| Glu70
| <cite>Ohnuma2014</cite>
|-
| [[GH20]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1c7s 1c7s]
| chitobiase
| ''Serratia marcescens''
| chitobiose
| '''Glu540'''
| internal
| <cite>Prag2000</cite>
|-
| [[GH22]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1h6m 1h6m]
| lysozyme C
| ''Gallus gallus''
| Chit-2-F-chitosyl
| '''Glu35'''
| Asp52
| <cite>Vocadlo2001</cite>
|-
| [[GH23]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1lsp 1lsp]
| lysozyme G
| ''Cygnus atratus''
| Bulgecin A
| '''Glu73'''
| internal
| <cite>Karlsen1996</cite>
|-
| [[GH24]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}148l 148l]
| lysozyme E
| Bacteriophage T4
| chitobiosyl
| '''Glu11'''
| Glu26
| <cite>Baldwin1993</cite>
|-
| [[GH26]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vx6 2vx6]
| exo-β-mannanase
| ''Cellvibrio japonicus'' Ueda107
| Gal1Man4
| '''Glu221'''
| Glu338
| <cite>Cartmell2008</cite>
|-
| [[GH27]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}} / beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3lrm 3lrm]
| α-galactosidase
| ''Saccharomyces cerevisiae''
| raffinose
| '''Asp209'''
| Asp141
| <cite>Fernandez-Leiro2010</cite>
|-
| [[GH28]]
| N
| β-helix
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}2uvf 2uvf]
| exo-polygalacturonosidase
| ''Yersinia enterocolitica'' ATCC9610D
| digalacturonic acid
| '''Asp402'''
| Asp381 Asp403
| <cite>Abbott2007</cite>
|-
| [[GH29]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| '''''syn'''''
| [{{PDBlink}}3uet 3uet]
| α-1,3/4-fucosidase
| ''Bifidobacterium longum'' subsp. infantis
| lacto-''N''-fucopentaose II
| '''Glu217'''
| Asp172
| <cite>Sakurama2012</cite>
|-
| [[GH30]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2y24 2y24]
| glucurono-xylanase
| ''Dickea chrysanthemi'' D1
| glucuronoxylan tetrasaccharide
| '''Glu163'''
| Glu253
| <cite>Urbanikova2011</cite>
|-
| [[GH31]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2qmj 2qmj]
| maltase-glucoamylase
| ''Homo sapiens''
| acarbose
| '''Asp542'''
| Asp443
| <cite>Sim2008</cite>
|-
| [[GH32]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2add 2add]
| fructan β-(2,1)-fructosidase
| ''Cichorium intybus''
| sucrose
| '''Glu201'''
| Asp22
| <cite>Verhaest2007</cite>
|-
| [[GH33]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1s0i 1s0i]
| transsialidase
| ''Trypanosoma cruzi''
| sialyllactose
| '''Asp59'''
| Tyr342
| <cite>Amaya2004</cite>
|-
| [[GH34]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzw 4gzw]
| N2 neuraminidase
| ''Influenza'' A Tanzania/205/2010 H3N2
| α-{{Smallcaps|d}}-Neup5Ac-(2,3)-β-{{Smallcaps|d}}-Galp-(1,4)-β-{{Smallcaps|d}}-GlcpNAc
| '''Asp151'''
| Tyr406
| <cite>Zhu2012</cite>
|-
| [[GH35]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3ogv 3ogv]
| β-galactosidase
| ''Hypocrea jecorina''
| 2-phenylethyl 1-thio-β-{{Smallcaps|d}}-galactopyranoside
| '''Glu200'''
| Glu298
| <cite>Maksimainen2011</cite>
|-
| [[GH36]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4fns 4fns]
| β-galactosidase
| ''Geobacillus stearothermophilus''
| 1-deoxy galactonojirimycin
| '''Asp584'''
| Asp478
| <cite>Merceron2012</cite>
|-
| [[GH37]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2jf4 2jf4]
| trehalase
| ''Escherichia coli''
| validoxylamine
| '''Asp312'''
| Glu496
| <cite>Gibson2007</cite>
|-
| [[GH38]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3czn 3czn]
| Golgi α-mannosidase II
| ''Drosophila melanogaster''
| GlcNAcMan(5)GlcNAc(2)
| '''Asp341'''
| Asp204
| <cite>Shah2008</cite>
|-
| [[GH39]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2bfg 2bfg]
| β-xylosidase
| ''Geobacillus stearothermophilus''
| 2,5-dinitrophenyl-β-{{Smallcaps|d}}-xyloside
| '''Glu160'''
| Glu278
| <cite>Czjzek2005</cite>
|-
| [[GH42]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ucf 4ucf]
| β-galactosidase
| ''Bifidobacterium bifidum''
| {{Smallcaps|d}}-galactose
| '''Glu161'''
| Glu320
| <cite>Godoy2016</cite>
|-
| [[GH43]]
| F
| 5-fold β-propeller
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3akh 3akh]
| exo-1,5-α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces avermitilis''
| α-1,5-arabinofuranotriose
| '''Glu196'''
| Asp220
| <cite>Fujimoto2010</cite>
|-
| [[GH44]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2eqd 2eqd]
| endoglucanase
| ''Clostridium thermocellum''
| cellooctaose
| '''Glu186'''
| Glu359
| <cite>Kitago2007</cite>
|-
| [[GH45]]
| none
| 6-stranded β-barrel
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4eng 4eng]
| endo-1,4-glucanase
| ''Humicola insolens''
| cellohexaose
| '''Asp121'''
| Asp10
| <cite>Davies1996</cite>
|-
| [[GH46]]
| I
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4olt 4olt]
| chitosanase
| ''Microbacterium sp.'' OU01
| hexa-glucosamine
| '''Glu25'''
| Asp43
| <cite>Lyu2014</cite>
|-
| [[GH47]]
| none
| (α/α)7
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1x9d 1x9d]
| α-mannosidase I
| ''Homo sapiens''
| Me-2-S-(α-Man)-2-thio-α-Man
| '''Asp463'''
| Glu599
| <cite>Karaveg2005</cite>, <cite>Nerinckx2008</cite>
|-
| [[GH48]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH8''
|
|
|
|
|
|
|-
| [[GH49]]
| N
| β-helix
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH28''
|
|
|
|
|
|
|-
| [[GH50]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4bq5 4bq5]
| exo-β-agarase
| ''Saccharophagus degradans''
| neoagarotetraose
| '''Glu535'''
| Glu695
| <cite>Pluvinage2013</cite>
|-
| [[GH51]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1qw9 1qw9]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Geobacillus stearothermophilus''
| PNP-{{Smallcaps|l}}-arabinofuranoside
| '''Glu175'''
| Glu294
| <cite>Hoevel2003</cite>
|-
| [[GH52]]
| O
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4c1p 4c1p]
| β-xylosidase
| ''Geobacillus thermoglucosidasius''
| xylobiose
| '''Asp517'''
| Glu537
| <cite>Espina2014</cite>
|-
| [[GH53]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2ccr 2ccr]
| β-1,4-galactanase
| ''Bacillus licheniformis''
| galactotriose
| '''Glu165'''
| Glu263
| <cite>Le_Nours2009</cite>
|-
| [[GH54]]
| none
| β-sandwich
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1wd4 1wd4]
| α-{{Smallcaps|l}}-arabinofuranosidase B
| ''Aspergillus kawachii''
| {{Smallcaps|l}}-arabinofuranose
| '''Asp297'''
| Glu221
| <cite>Miyanaga2004</cite>
|-
| [[GH55]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4tz5 4tz5]
| exo-β-1,3-glucanase
| ''Streptomyces sp.'' SirexAA-E
| laminarihexaose
| '''Glu502'''
| unknown
| <cite>Bianchetti2015</cite>
|-
| [[GH56]]
| none
| (β/α)7
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1fcv 1fcv]
| hyaluronidase
| ''Apis mellifera''
| (hyaluron.)4
| '''Glu113'''
| internal
| <cite>Markovic-Housley2000</cite>
|-
| [[GH57]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1k1y 1k1y]
| glucanotransferase
| ''Thermococcus litoralis''
| acarbose
| '''Asp214'''
| Glu123
| <cite>Imamura2003</cite>
|-
| [[GH59]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ccc 4ccc]
| β-galactocerebrosidase
| ''Mus musculus''
| PNP-β-{{Smallcaps|d}}-galactoside
| '''Glu182'''
| Glu258
| <cite>Hill2013</cite>
|-
| [[GH62]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| ''predicted anti by clan''
| ''see at GH43''
|
|
|
|
|
|
|-
| [[GH63]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5ca3 5ca3]
| α-glucosidase
| ''Escherichia coli''
| glucose and lactose
| '''Asp501'''
| Glu727
| <cite>Miyazaki2016</cite>
|-
| [[GH65]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}4ktr 4ktr]
| 2-O-α-glucosylglycerol phosphorylase
| ''Bacillus selenitireducens''
| isofagomine
| '''Glu475'''
| phosphate
| <cite>Touhara2014</cite>
|-
| [[GH66]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5axh 5axh]
| dextranase
| ''Thermoanaerobacter pseudethanolicus''
| isomaltohexaose
| '''Glu374'''
| Asp312
| <cite>Suzuki2016</cite>
|-
| [[GH67]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1l8n 1l8n]
| α-glucuronidase
| ''Geobacillus stearothermophilus''
| 4-O-methyl-{{Smallcaps|d}}-glucuronic acid and xylotriose
| '''Glu286'''
| Asp364 Glu392
| <cite>Golan2004</cite>
|-
| [[GH68]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1pt2 1pt2]
| levansucrase
| ''Bacillus subtilis''
| sucrose
| '''Glu342'''
| Asp86
| <cite>Meng2003</cite>
|-
| [[GH70]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3aic 3aic]
| glucansucrase
| ''Streptococcus mutans''
| α-acarbose
| '''Glu515'''
| Asp477
| <cite>Ito2011</cite>
|-
| [[GH72]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w62 2w62]
| β-1,3-glucanotransferase
| ''Saccharomyces cerevisiae'' S288C
| laminaripentaose
| '''Glu176'''
| Glu275
| <cite>Hurtado-Gerrero2009</cite>
|-
| [[GH74]]
| none
| 7-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}2ebs 2ebs]
| cellobiohydrolase (OXG-RCBH)
| ''Geotrichum sp.'' m128
| xyloglucan heptasaccharide
| '''Asp465'''
| Asp35
| <cite>Yaoi2007</cite>
|-
| [[GH76]]
| none
| (α/α)6
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5agd 5agd]
| endo-α-1,6-mannanase
| ''Bacillus circulans''
| α-1,6-mannopentaose
| '''Asp125'''
| Asp124
| <cite>Thompson2015</cite>
|-
| [[GH77]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2oww 2oww]
| 4-α-glucanotransferase
| ''Thermus thermofilus''
| acarbose + 4-deoxy-α-{{Smallcaps|d}}-glucose
| '''Glu340'''
| Asp293
| <cite>Barends2007</cite>
|-
| [[GH78]]
| H
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3w5n 3w5n]
| α-{{Smallcaps|l}}-rhamnosidase
| ''Streptomyces avermitilis''
| {{Smallcaps|l}}-rhamnose
| '''Glu636'''
| Glu895
| <cite>Fujimoto2013</cite>
|-
| [[GH79]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5e9c 5e9c]
| heparanase
| ''Homo sapiens''
| heparin tetrasaccharide
| '''Glu225'''
| Glu343
| <cite>Wu2015</cite>
|-
| [[GH80]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH24''
|
|
|
|
|
|
|-
| [[GH81]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5t4g 5t4g]
| endo-β-1,3-glucanase
| ''Bacillus halodurans'' C-125
| laminarin
| '''Asp466'''
| Glu542
| <cite>Pluvinage2017</cite>
|-
| [[GH83]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH33''
|
|
|
|
|
|
|-
| [[GH84]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2chn 2chn]
| β-''N''-acetyl-glucosaminidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| NAG-thiazoline
| '''Glu242'''
| internal
| <cite>Dennis2006</cite>
|-
| [[GH85]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w92 2w92]
| endo-β-''N''-acetyl-glucosaminidase D
| ''Streptococcus pneumoniae'' TIGR4
| NAG-thiazoline
| '''Glu337'''
| internal
| <cite>Abbott2009</cite>
|-
| [[GH86]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4aw7 4aw7]
| β-porphyranase
| ''Bacteroides plebeius''
| porphyran fragment
| '''Glu152'''
| Glu279
| <cite>Hehemann_1_2012</cite>
|-
| [[GH89]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vcb 2vcb]
| α-''N''-acetyl-glucosaminidase
| ''Clostridium perfringens''
| PUGNAc
| '''Glu483'''
| Glu601
| <cite>Ficko-Blean2008</cite>
|-
| [[GH92]]
| none
| (α/α)6 and β-sandwich
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ww1 2ww1]
| α-1,2-mannosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| thiomannobioside
| '''Glu533'''
| Asp644 Asp642
| <cite>Zhu2009</cite>
|-
| [[GH93]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3a72 3a72]
| exo-arabinanase
| ''Penicillium chrysogenum''
| arabinobiose
| '''Glu246'''
| Glu174
| <cite>Sogabe2011</cite>
|-
| [[GH94]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4zli 4zli]
| cellobionic acid phosphorylase
| ''Saccharophagus degradans''
| 3-O-β-{{Smallcaps|d}}-glucopyranosyl-α-{{Smallcaps|d}}-glucopyranuronic acid
| '''Asp472'''
| phosphate
| <cite>Nam2015</cite>
|-
| [[GH95]]
| none
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ead 2ead]
| α-1,2-{{Smallcaps|l}}-fucosidase
| ''Bifidobacterium bifidum''
| Fuc-α-1,2-Gal
| '''Glu566'''
| Asn423 Asp766
| <cite>Nagae2007</cite>
|-
| [[GH97]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining + inverting
| '''''anti'''''
| [{{PDBlink}}2zq0 2zq0]
| α-glucosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| acarbose
| '''Glu532'''
| Glu508
| <cite>Kitamura2008</cite>
|-
| [[GH98]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2wmg 2wmg]
| endo-β-1,4-galactosidase
| ''Streptococcus pneumoniae''
| A-LewisY pentasaccharide
| '''Glu158'''
| Asp251 Glu301
| <cite>Higgins2009</cite>
|-
| [[GH99]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ad4 4ad4]
| endo-α-mannosidase
| ''Bacteroides xylanisolvens''
| glucose-1,3-isofagomine and α-1,2- mannobiose
| '''Glu336'''
| debated
| <cite>Thompson2012</cite>
|-
| [[GH100]]
| none
| (α/α)6 core
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5gop 5gop]
| invertase
| ''Anabaena (Nostoc) sp.'' pcc7120
| sucrose
| '''Asp188'''
| Glu414
| <cite>Xie2016</cite>
|-
| [[GH102]]
| none
| double-ψ β-barrel
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}2pi8 2pi8]
| lytic transglycosylase A
| ''Escherichia coli''
| chitohexaose
| '''Asp308'''
| none
| <cite>van_Straaten2007</cite>
|-
| [[GH103]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1d0k 1d0k]
| lytic transglycosylase SLT35
| ''Escherichia coli''
| murodipeptides
| '''Glu162'''
| internal
| <cite>van_Asselt2000</cite>
|-
| [[GH106]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5mwk 5mwk]
| α-{{Smallcaps|l}}-rhamnosidase BT_0986
| ''Bacteroides thetaiotaomicron''
| pectin heptasaccharide
| '''Glu461'''
| Glu593 or Glu561
| <cite>Ndeh2017</cite>
|-
| [[GH107]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| ''predicted syn by clan''
| ''see at GH29''
|
|
|
|
|
|
|-
| [[GH113]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4cd8 4cd8]
| β-mannanase
| ''Alicyclobacillus acidocaldarius''
| mannobioimidazole
| '''Glu151'''
| Glu231
| <cite>Williams2014</cite>
|-
| [[GH116]]
| O
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at GH52''
|
|
|
|
|
|
|-
| [[GH117]]
| none
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}4ak7 4ak7]
| α-1,3-3,6-anhydro-{{Smallcaps|l}}-galactosidase
| ''Bacteroides plebeius''
| neoagarobiose
| '''His302'''
| Asp90
| <cite>Hehemann_2_2012</cite>
|-
| [[GH120]]
| none
| parallel β-helix and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3vsv 3vsv]
| β-xylosidase XylC
| ''Thermoanaerobacterium saccharolyticum'' JW/SL-YS485
| {{Smallcaps|d}}-xylose
| '''Glu405'''
| Asp382
| <cite>Huang2012</cite>
|-
| [[GH123]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5fr0 5fr0]
| exo-β-N-acetyl-galactosaminidase
| ''Clostridium perfringens''
| ''N''-difluoroacetyl-{{Smallcaps|d}}-galactosamine
| '''Glu345'''
| internal
| <cite>Noach2016</cite>
|-
| [[GH125]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5m7y 5m7y]
| exo-α-1,6-mannosidase
| ''Clostridium perfringens''
| 1,6-α-mannotriose
| '''Asp220'''
| Glu393
| <cite>Alonso-Gil2016</cite>
|-
| [[GH127]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3wrg 3wrg]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bifidobacterium longum''
| {{Smallcaps|l}}-arabinose
| '''Glu322'''
| Cys417
| <cite>Huang2014</cite>
|-
| [[GH128]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH1''
|
|
|
|
|
|
|-
| [[GH130]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5b0s 5b0s]
| β-1,2-mannobiose phosphorylase
| ''Listeria innocua''
| β-1,2-mannotriose
| '''Asp141''' relay
| phosphate
| <cite>Tsuda2015</cite>
|-
| [[GH134]]
| none
| β + α
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5jug 5jug]
| β-mannanase
| ''Streptomyces sp.''
| mannopentaose
| '''Glu45'''
| Asp57
| <cite>Jin2016</cite>
|-
| [[GH136]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}5gqf 5gqf]
| lacto-N-biosidase
| ''Bifidobacterium longum''
| lacto-N-biose
| '''Asp411'''
| Asp418
| <cite>Yamada2017</cite>
|-
| [[GH137]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|l}}
| unknown
| '''''anti'''''
| [{{PDBlink}}5mui 5mui]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0996
| ''Bacteroides thetaiotaomicron''
| pectin oligosaccharide
| '''Glu240'''
| Glu159
| <cite>Ndeh2017</cite>
|-
| [[GH146]]
| P
| (α/α)6
| beta-{{Smallcaps|l}}
| retaining
| ''predicted anti by clan''
| ''see at GH127''
|
|
|
|
|
|
|-
| [[GH147]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH148]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH149]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [http://www.cazy.org/GH0.html n.c.*]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2vjj 2vjj]
| endo-α-N-acetylglucosaminidase
| Bacteriophage HK620
| O18A1 O-antigen hexasaccharide
| '''Asp339'''
| Glu372
| <cite>Barbirz2008</cite>
|}
<nowiki>*</nowiki> n.c.: Found among the collection of [http://www.cazy.org/GH0.html non-classified GH sequences in the CAZy Database].

== References ==

<biblio>
# HeightmanVasella1999 Heightman TD and Vasella AT. ''Recent Insights into Inhibition, Structure, and Mechanism of Configuration-Retaining Glycosidases.'' Angew Chem Int Ed. 1999 38(6):750-770. [http://www3.interscience.wiley.com/journal/55000581/abstract Article online].
# Nerinckx2005 pmid=15642336
# Wu2012 pmid=23137336
# Perez1978 Pérez S and Marchessault RH. ''The exo-anomeric effect: experimental evidence from crystal structures.'' Carbohydr res. 1978 65:114-120. [http://dx.doi.org/10.1016/S0008-6215(00)84218-4 DOI:10.1016/S0008-6215(00)84218-4]
# Cramer1997 Cramer CJ, Truhlar DG, and French AD. ''Exo-anomeric effects on energies and geometries of different conformations of glucose and related systems in the gas phase and aqueous solution.'' Carbohydr res. 1997 298:1-14. [http://dx.doi.org/10.1016/S0008-6215(96)00297-2 DOI:10.1016/S0008-6215(96)00297-2]
# Johnson2009 pmid=19733839
# Alonso2016 pmid=26889578
# Gloster2006 pmid=17002288
# van_Bueren2009 pmid=18976664
# Hrmova2001 pmid=11709165
# Varrot2003 pmid=12595701
# Zhou1999 pmid=10508787
# Sulzenbacher1999 pmid=10200171
# Urbanikova2011 pmid=21501386
# Guerin2002 pmid=11884144
# Schubot2004 pmid=14756552
# Suzuki2009 pmid=19279191
# Wan2014 pmid=24419374
# Sandgren2004 pmid=15364577
# Uitdehaag1999 pmid=10331869
# Miyake2003 pmid=12741813
# Harris1993 pmid=8431441
# Allouch2004 pmid=15062085
# Papanikolau2001 pmid=11560481
# Prag2000 pmid=10884356
# Vocadlo2001 pmid=11518970
# Karlsen1996 pmid=15299731
# Baldwin1993 pmid=8259514
# Cartmell2008 pmid=18799462
# Fernandez-Leiro2010 pmid=20592022
# Abbott2007 pmid=17397864
# Sakurama2012 pmid=22451675
# Sim2008 pmid=18036614
# Verhaest2007 pmid=17335500
# Amaya2004 pmid=15130470
# Zhu2012 pmid=23015718
# Maksimainen2011 pmid=21130883
# Merceron2012 pmid=23012371
# Gibson2007 pmid=17455176
# Shah2008 pmid=18599462
# Czjzek2005 pmid=16212978
# Godoy2016 pmid=27685756
# Fujimoto2010 pmid=20739278
# Kitago2007 pmid=17905739
# Davies1996 pmid=15299721
# Lyu2014 pmid=24766439
# Karaveg2005 pmid=15713668
# Nerinckx2008 pmid=18619586
# Pluvinage2013 pmid=23921382
# Hoevel2003 pmid=14517232
# Espina2014 pmid=24816105
# Le_Nours2009 pmid=19089956
# Miyanaga2004 pmid=15292273
# Bianchetti2015 pmid=25752603
# Markovic-Housley2000 pmid=11080624
# Imamura2003 pmid=12618437
# Hill2013 pmid=24297913
# Miyazaki2016 pmid=27688023
# Touhara2014 pmid=24828502
# Suzuki2016 pmid=26494689
# Golan2004 pmid=14573597
# Meng2003 pmid=14517548
# Ito2011 pmid=21354427
# Hurtado-Gerrero2009 pmid=19097997
# Yaoi2007 pmid=17498741
# Thompson2015 pmid=25772148
# Barends2007 pmid=17420245
# Fujimoto2013 pmid=23486481
# Wu2015 pmid=26575439
# Pluvinage2017 pmid=28781080
# Dennis2006 pmid=16565725
# Abbott2009 pmid=19181667
# Hehemann_1_2012 pmid=23150581
# Ficko-Blean2008 pmid=18443291
# Zhu2009 pmid=20081828
# Sogabe2011 pmid=21543843
# Nam2015 pmid=26041776
# Nagae2007 pmid=17459873
# Kitamura2008 pmid=18981178
# Higgins2009 pmid=19608744
# van_Straaten2007 pmid=17502382
# van_Asselt2000 pmid=10684641
# Ndeh2017 pmid=28329766
# Jin2016 Jin Y, Petricevic M, John A, Raich L, Jenkins H, Portela De Souza L, Cuskin F, Gilbert HJ, Rovira C, Goddard-Borger ED, Williams SJ, and Davies GJ. ''A β-Mannanase with a Lysozyme-like Fold and a Novel Molecular Catalytic Mechanism.'' ACS Cent Sci. 2016 Nov [http://dx.doi.org/10.1021/acscentsci.6b00232 DOI:10.1021/acscentsci.6b00232]
# Yamada2017 pmid=28392148
# Ohnuma2014 pmid=24582745
# Thompson2012 pmid=22219371
# Xie2016 pmid=27777307
# Williams2014 pmid=24339341
# Hehemann_2_2012 pmid=22393053
# Huang2012 pmid=22992047
# Noach2016 pmid=27038508
# Alonso-Gil2016 pmid=28026180
# Huang2014 Huang CH, Zhu Z, Cheng YS, Chan HC, Ko TP, Chen CC, Wang I, Ho MR, Hsu ST, Zeng YF, Huang YN, Liu JR, Guo RT. ''Structure and Catalytic Mechanism of a Glycoside Hydrolase Family-127 β-L-Arabinofuranosidase (HypBA1).'' J Bioprocess Biotech. 2014 4:171 [http://dx.doi.org/10.4172/2155-9821.1000171 DOI:10.4172/2155-9821.1000171]
# Tsuda2015 pmid=26632508
# Barbirz2008 pmid=18547389

</biblio>

[[Category:Definitions and explanations]]

Syn/anti lateral protonation

2018-10-20T08:30:33Z

Wim Nerinckx:

{{CuratorApproved}}
* [[Author]]: ^^^Wim Nerinckx^^^
* [[Responsible Curator]]: ^^^Spencer Williams^^^

----

== Overview ==

This page provides a table that summarizes the spatial positioning of the catalytic [[general acid]] residue in the active sites of [[glycoside hydrolase]]s, relative to the substrate. The table below updates those found in the seminal paper on this concept by Heightman and Vasella <cite>HeightmanVasella1999</cite>, and a following paper by Nerinckx ''et al.'' <cite>Nerinckx2005</cite>.

== Background ==

The ''"not from above, but from the side"'' concept of semi-lateral glycosidic oxygen [[General_acid/base|protonation]] by [[glycoside hydrolase]]s was introduced by Heightman and Vasella <cite>HeightmanVasella1999</cite>. It was originally only described for [[Anomeric centre (alpha and beta)|beta]]-equatorial [[glycoside hydrolase]]s, but appears to be equally applicable to enzymes acting on an [[Anomeric centre (alpha and beta)|alpha]]-axial glycosidic bond <cite>Nerinckx2005</cite>. When dividing [[Sub-site nomenclature|subsite -1]] into half-spaces by a plane defined by the glycosidic oxygen and C1' and H1' of the –1 glycoside, many ligand-complexed structures reveal that the [[General_acid/base|proton donor]] is positioned either in the ''syn'' half-space (near the ring-oxygen of the –1 glycoside), or in the ''anti'' half-space (on the opposite side of the ring-oxygen). Members of the same GH [[Families|family]] appear to share a common ''syn'' or ''anti'' [[General_acid/base|protonator]] arrangement and further, this specificity appears to be preserved within [[Clans|Clans]] of [[Families|families]]. This page's compilation of [[Sub-site nomenclature|subsite -1]] occupied complexes shows that about 70% of all GH [[Families|families]] are ''anti'' [[General_acid/base|protonators]].

Closer inspection of crystal structures of [[Sub-site nomenclature|–1/+1 subsite]]-spanning substrates, or substrate-analogue ligands, in complex with enzymes reveals a further intriguing corollary <cite>Nerinckx2005 Wu2012</cite>. In substrate-bound complexes with ''anti'' [[General_acid/base|protonating]] GH enzymes, the scissile [[Anomeric centre (alpha and beta)|anomeric bond]] (often studied using the thio-analogue) shows a dihedral angle φ (O5'-C1'-[O,S]x-Cx) that is in the lowest-energy synclinal (gauche) conformation. The rationale for this is that a minus synclinal dihedral angle φ for an equatorial glycosidic bond, or plus synclinal for an axial glycosidic bond <cite>Perez1978</cite>, allows for hyperconjugative overlap of the C1'-O5' antibonding orbital with an antiperiplanar-oriented lone pair orbital lobe of the glycosidic oxygen, thereby creating partial double bond character and stabilization of the glycosidic bond by 4–5 kcal/mol; this ground-state stabilizing phenomenon is known as the ‘exo-anomeric effect’ <cite>Cramer1997 Johnson2009 Alonso2016</cite>. ''Anti'' [[General_acid/base|protonation]] occurs on the glycosidic oxygen’s antiperiplanar lone pair, thereby removing the stabilizing exo-anomeric effect. This suggests that ''anti'' [[General_acid/base|protonation]] is an enzymic approach for lowering the activation barrier leading to the [[Transition state|transition state]] (Figure 1 centre).

''Syn'' [[General_acid/base|protonating]] [[glycoside hydrolase]]s apparently make use of a different approach <cite>Nerinckx2005 Wu2012</cite>. In many [[Sub-site nomenclature|–1/+1 subsite]]-spanning ligand complexes, the dihedral angle φ of the scissile anomeric bond has been rotated away from its lowest-energy synclinal position: clockwise to minus-anticlinal or antiperiplanar for beta-equatorial; counterclockwise to plus-anticlinal or antiperiplanar for alpha-axial [[Anomeric centre (alpha and beta)|anomeric bonds]]. This removes the hyperconjugative overlap and thus also the stabilizing exo-anomeric effect. And because of this rotation, a lone pair of the glycosidic oxygen is directed into the ''syn'' half-space, allowing it to be protonated by the ''syn''-positioned [[General_acid/base|proton donor]] (Figure 1 right).

[[File:Syn_anti.jpg|800px|thumb|center|Figure 1. Newman projections, with the glycosidic oxygen as proximal atom and the anomeric carbon as distal atom, showing ''anti'' (centre) versus ''syn'' (right) semi-lateral [[General_acid/base|protonation]] in beta-equatorial (top) and alpha-axial (bottom) [[glycoside hydrolase]]s. The indicated φ is the dihedral angle for O5'-C1'-O4-C4.]]

== Table of ''syn/anti'' protonation examples ==

This table contains only one example per GH [[Families|family]] of a ligand-complexed protein structure where the ''syn'' or ''anti'' positioning of the [[General_acid/base|proton donor]] can be clearly observed; other examples may be available on a [[Families|family-by-family]] basis. The reader is thus advised to consult the [http://www.cazy.org/fam/acc_GH.html#table CAZy database] for a current, comprehensive list of CAZyme structures. Where available, the selected examples are Michaelis-type complexes with the ligand spanning the [[Sub-site nomenclature|-1/+1 subsites]], since these have an intact glycosidic or thioglycosidic bond, or are ''N''-analogs of the substrate (''e.g.'' acarbose). In some examples, the [[General_acid/base|proton donor]] has been mutated (''e.g.'', to the corresponding amide or to an alanine), and in those cases one may wish to look at a superposition of the given PDB example with the structure of the native enzyme. If a Michaelis-type complex is not yet available, the second and third example choices, respectively, are trapped glycosyl-enzyme [[intermediate]]s and product complexes where [[Sub-site nomenclature|subsite -1]] is occupied.

''Please also be aware that this is a large table with many data. Please contact the page Author or Responsible Curator with corrections.''

=== Table ===
This table can be re-sorted by clicking on the icons in the header (''javascript must be turned on in your browser''). To reset the page to be sorted by GH family, click the ''View'' tab at the very top of the page.

{| {{Prettytable}} class="sortable"
|- valign="top"
! '''Family'''
! '''Clan'''
! '''Structure fold '''
! '''Anomeric specificity'''
! '''Mechanism'''
! '''''Syn/anti'' protonator'''
! '''Example PDB ID'''
! '''Enzyme'''
! '''Organism'''
! '''Ligand'''
! '''General acid'''
! '''Nucleophile or General base'''
! '''Reference'''
|-
| [[GH1]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2cer 2cer]
| β-glycosidase S
| ''Sulfolobus solfataricus'' P2
| phenethyl glucoimidazole
| '''Glu206'''
| Glu387
| <cite>Gloster2006</cite>
|-
| [[GH2]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vzu 2vzu]
| exo-β-glucosaminidase
| ''Amicolatopsis orientalis''
| PNP-β-{{Smallcaps|d}}-glucosamine
| '''Glu469'''
| Glu541
| <cite>van_Bueren2009</cite>
|-
| [[GH3]]
| none
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1iex 1iex]
| exo-1,3-1,4-glucanase
| ''Hordeum vulgare''
| thiocellobiose
| '''Glu491'''
| Asp285
| <cite>Hrmova2001</cite>
|-
| [[GH5]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1h2j 1h2j]
| endo-β-1,4-glucanase
| ''Bacillus agaradhaerens''
| 2',4'-DNP-2-F-cellobioside
| '''Glu129'''
| Glu228
| <cite>Varrot2003</cite>
|-
| [[GH6]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1qjw 1qjw]
| cellobiohydrolase 2
| ''Hypocrea jecorina''
| (Glc)2-S-(Glc)2
| '''Asp221'''
| debated
| <cite>Zhou1999</cite>
|-
| [[GH7]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1ovw 1ovw]
| endo-1,4-glucanase
| ''Fusarium oxysporum''
| thio-(Glc)5
| '''Glu202'''
| Glu197
| <cite>Sulzenbacher1999</cite>
|-
| [[GH8]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1kwf 1kwf]
| endo-1,4-glucanase
| ''Clostridium thermocellum''
| cellopentaose
| '''Glu95'''
| Asp278
| <cite>Guerin2002</cite>
|-
| [[GH9]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1rq5 1rq5]
| cellobiohydrolase
| ''Clostridium thermocellum''
| cellotetraose
| '''Glu795'''
| Asp383
| <cite>Schubot2004</cite>
|-
| [[GH10]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2d24 2d24]
| β-1,4-xylanase
| ''Streptomyces olivaceoviridis'' E-86
| xylopentaose
| '''Glu128'''
| Glu236
| <cite>Suzuki2009</cite>
|-
| [[GH11]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}4hk8 4hk8]
| endo-β-1,4-xylanase
| ''Hypocrea jecorina''
| xylohexaose
| '''Glu177'''
| Glu86
| <cite>Wan2014</cite>
|-
| [[GH12]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1w2u 1w2u]
| endoglucanase
| ''Humicola grisea''
| thiocellotetraose
| '''Glu205'''
| Glu120
| <cite>Sandgren2004</cite>
|-
| [[GH13]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1cxk 1cxk]
| β-cyclodextrin glucanotransferase
| ''Bacillus circulans''
| maltononaose
| '''Glu257'''
| Asp229
| <cite>Uitdehaag1999</cite>
|-
| [[GH14]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1itc 1itc]
| β-amylase
| ''Bacillus cereus''
| maltopentaose
| '''Glu172'''
| Glu367
| <cite>Miyake2003</cite>
|-
| [[GH15]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1dog 1dog]
| glucoamylase
| ''Aspergillus awamori''
| 1-deoxynojirimycin
| '''Glu179'''
| Glu400
| <cite>Harris1993</cite>
|-
| [[GH16]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1urx 1urx]
| β-agarase A
| ''Zobellia galactanivorans''
| oligoagarose
| '''Glu152'''
| Glu147
| <cite>Allouch2004</cite>
|-
| [[GH17]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH1''
|
|
|
|
|
|
|-
| [[GH18]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1ffr 1ffr]
| chitinase A
| ''Serratia marcescens''
| (NAG)6
| '''Glu315'''
| internal
| <cite>Papanikolau2001</cite>
|-
| [[GH19]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}3wh1 3wh1]
| chitinase
| ''Bryum coronatum''
| (GlcNAc)4
| '''Glu61'''
| Glu70
| <cite>Ohnuma2014</cite>
|-
| [[GH20]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1c7s 1c7s]
| chitobiase
| ''Serratia marcescens''
| chitobiose
| '''Glu540'''
| internal
| <cite>Prag2000</cite>
|-
| [[GH22]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1h6m 1h6m]
| lysozyme C
| ''Gallus gallus''
| Chit-2-F-chitosyl
| '''Glu35'''
| Asp52
| <cite>Vocadlo2001</cite>
|-
| [[GH23]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1lsp 1lsp]
| lysozyme G
| ''Cygnus atratus''
| Bulgecin A
| '''Glu73'''
| internal
| <cite>Karlsen1996</cite>
|-
| [[GH24]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}148l 148l]
| lysozyme E
| Bacteriophage T4
| chitobiosyl
| '''Glu11'''
| Glu26
| <cite>Baldwin1993</cite>
|-
| [[GH26]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vx6 2vx6]
| exo-β-mannanase
| ''Cellvibrio japonicus'' Ueda107
| Gal1Man4
| '''Glu221'''
| Glu338
| <cite>Cartmell2008</cite>
|-
| [[GH27]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}} / beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3lrm 3lrm]
| α-galactosidase
| ''Saccharomyces cerevisiae''
| raffinose
| '''Asp209'''
| Asp141
| <cite>Fernandez-Leiro2010</cite>
|-
| [[GH28]]
| N
| β-helix
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}2uvf 2uvf]
| exo-polygalacturonosidase
| ''Yersinia enterocolitica'' ATCC9610D
| digalacturonic acid
| '''Asp402'''
| Asp381 Asp403
| <cite>Abbott2007</cite>
|-
| [[GH29]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| '''''syn'''''
| [{{PDBlink}}3uet 3uet]
| α-1,3/4-fucosidase
| ''Bifidobacterium longum'' subsp. infantis
| lacto-''N''-fucopentaose II
| '''Glu217'''
| Asp172
| <cite>Sakurama2012</cite>
|-
| [[GH30]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2y24 2y24]
| glucurono-xylanase
| ''Dickea chrysanthemi'' D1
| glucuronoxylan tetrasaccharide
| '''Glu163'''
| Glu253
| <cite>Urbanikova2011</cite>
|-
| [[GH31]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2qmj 2qmj]
| maltase-glucoamylase
| ''Homo sapiens''
| acarbose
| '''Asp542'''
| Asp443
| <cite>Sim2008</cite>
|-
| [[GH32]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2add 2add]
| fructan β-(2,1)-fructosidase
| ''Cichorium intybus''
| sucrose
| '''Glu201'''
| Asp22
| <cite>Verhaest2007</cite>
|-
| [[GH33]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1s0i 1s0i]
| transsialidase
| ''Trypanosoma cruzi''
| sialyllactose
| '''Asp59'''
| Tyr342
| <cite>Amaya2004</cite>
|-
| [[GH34]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzw 4gzw]
| N2 neuraminidase
| ''Influenza'' A Tanzania/205/2010 H3N2
| α-{{Smallcaps|d}}-Neup5Ac-(2,3)-β-{{Smallcaps|d}}-Galp-(1,4)-β-{{Smallcaps|d}}-GlcpNAc
| '''Asp151'''
| Tyr406
| <cite>Zhu2012</cite>
|-
| [[GH35]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3ogv 3ogv]
| β-galactosidase
| ''Hypocrea jecorina''
| 2-phenylethyl 1-thio-β-{{Smallcaps|d}}-galactopyranoside
| '''Glu200'''
| Glu298
| <cite>Maksimainen2011</cite>
|-
| [[GH36]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4fns 4fns]
| β-galactosidase
| ''Geobacillus stearothermophilus''
| 1-deoxy galactonojirimycin
| '''Asp584'''
| Asp478
| <cite>Merceron2012</cite>
|-
| [[GH37]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2jf4 2jf4]
| trehalase
| ''Escherichia coli''
| validoxylamine
| '''Asp312'''
| Glu496
| <cite>Gibson2007</cite>
|-
| [[GH38]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3czn 3czn]
| Golgi α-mannosidase II
| ''Drosophila melanogaster''
| GlcNAcMan(5)GlcNAc(2)
| '''Asp341'''
| Asp204
| <cite>Shah2008</cite>
|-
| [[GH39]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2bfg 2bfg]
| β-xylosidase
| ''Geobacillus stearothermophilus''
| 2,5-dinitrophenyl-β-{{Smallcaps|d}}-xyloside
| '''Glu160'''
| Glu278
| <cite>Czjzek2005</cite>
|-
| [[GH42]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ucf 4ucf]
| β-galactosidase
| ''Bifidobacterium bifidum''
| {{Smallcaps|d}}-galactose
| '''Glu161'''
| Glu320
| <cite>Godoy2016</cite>
|-
| [[GH43]]
| F
| 5-fold β-propeller
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3akh 3akh]
| exo-1,5-α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces avermitilis''
| α-1,5-arabinofuranotriose
| '''Glu196'''
| Asp220
| <cite>Fujimoto2010</cite>
|-
| [[GH44]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2eqd 2eqd]
| endoglucanase
| ''Clostridium thermocellum''
| cellooctaose
| '''Glu186'''
| Glu359
| <cite>Kitago2007</cite>
|-
| [[GH45]]
| none
| 6-stranded β-barrel
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4eng 4eng]
| endo-1,4-glucanase
| ''Humicola insolens''
| cellohexaose
| '''Asp121'''
| Asp10
| <cite>Davies1996</cite>
|-
| [[GH46]]
| I
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4olt 4olt]
| chitosanase
| ''Microbacterium sp.'' OU01
| hexa-glucosamine
| '''Glu25'''
| Asp43
| <cite>Lyu2014</cite>
|-
| [[GH47]]
| none
| (α/α)7
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1x9d 1x9d]
| α-mannosidase I
| ''Homo sapiens''
| Me-2-S-(α-Man)-2-thio-α-Man
| '''Asp463'''
| Glu599
| <cite>Karaveg2005</cite>, <cite>Nerinckx2008</cite>
|-
| [[GH48]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH8''
|
|
|
|
|
|
|-
| [[GH49]]
| N
| β-helix
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH28''
|
|
|
|
|
|
|-
| [[GH50]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4bq5 4bq5]
| exo-β-agarase
| ''Saccharophagus degradans''
| neoagarotetraose
| '''Glu535'''
| Glu695
| <cite>Pluvinage2013</cite>
|-
| [[GH51]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1qw9 1qw9]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Geobacillus stearothermophilus''
| PNP-{{Smallcaps|l}}-arabinofuranoside
| '''Glu175'''
| Glu294
| <cite>Hoevel2003</cite>
|-
| [[GH52]]
| O
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4c1p 4c1p]
| β-xylosidase
| ''Geobacillus thermoglucosidasius''
| xylobiose
| '''Asp517'''
| Glu537
| <cite>Espina2014</cite>
|-
| [[GH53]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2ccr 2ccr]
| β-1,4-galactanase
| ''Bacillus licheniformis''
| galactotriose
| '''Glu165'''
| Glu263
| <cite>Le_Nours2009</cite>
|-
| [[GH54]]
| none
| β-sandwich
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1wd4 1wd4]
| α-{{Smallcaps|l}}-arabinofuranosidase B
| ''Aspergillus kawachii''
| {{Smallcaps|l}}-arabinofuranose
| '''Asp297'''
| Glu221
| <cite>Miyanaga2004</cite>
|-
| [[GH55]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4tz5 4tz5]
| exo-β-1,3-glucanase
| ''Streptomyces sp.'' SirexAA-E
| laminarihexaose
| '''Glu502'''
| unknown
| <cite>Bianchetti2015</cite>
|-
| [[GH56]]
| none
| (β/α)7
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1fcv 1fcv]
| hyaluronidase
| ''Apis mellifera''
| (hyaluron.)4
| '''Glu113'''
| internal
| <cite>Markovic-Housley2000</cite>
|-
| [[GH57]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1k1y 1k1y]
| glucanotransferase
| ''Thermococcus litoralis''
| acarbose
| '''Asp214'''
| Glu123
| <cite>Imamura2003</cite>
|-
| [[GH59]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ccc 4ccc]
| β-galactocerebrosidase
| ''Mus musculus''
| PNP-β-{{Smallcaps|d}}-galactoside
| '''Glu182'''
| Glu258
| <cite>Hill2013</cite>
|-
| [[GH62]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| ''predicted anti by clan''
| ''see at GH43''
|
|
|
|
|
|
|-
| [[GH63]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5ca3 5ca3]
| α-glucosidase
| ''Escherichia coli''
| glucose and lactose
| '''Asp501'''
| Glu727
| <cite>Miyazaki2016</cite>
|-
| [[GH65]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}4ktr 4ktr]
| 2-O-α-glucosylglycerol phosphorylase
| ''Bacillus selenitireducens''
| isofagomine
| '''Glu475'''
| phosphate
| <cite>Touhara2014</cite>
|-
| [[GH66]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5axh 5axh]
| dextranase
| ''Thermoanaerobacter pseudethanolicus''
| isomaltohexaose
| '''Glu374'''
| Asp312
| <cite>Suzuki2016</cite>
|-
| [[GH67]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1l8n 1l8n]
| α-glucuronidase
| ''Geobacillus stearothermophilus''
| 4-O-methyl-{{Smallcaps|d}}-glucuronic acid and xylotriose
| '''Glu286'''
| Asp364 Glu392
| <cite>Golan2004</cite>
|-
| [[GH68]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1pt2 1pt2]
| levansucrase
| ''Bacillus subtilis''
| sucrose
| '''Glu342'''
| Asp86
| <cite>Meng2003</cite>
|-
| [[GH70]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3aic 3aic]
| glucansucrase
| ''Streptococcus mutans''
| α-acarbose
| '''Glu515'''
| Asp477
| <cite>Ito2011</cite>
|-
| [[GH72]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w62 2w62]
| β-1,3-glucanotransferase
| ''Saccharomyces cerevisiae'' S288C
| laminaripentaose
| '''Glu176'''
| Glu275
| <cite>Hurtado-Gerrero2009</cite>
|-
| [[GH74]]
| none
| 7-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}2ebs 2ebs]
| cellobiohydrolase (OXG-RCBH)
| ''Geotrichum sp.'' m128
| xyloglucan heptasaccharide
| '''Asp465'''
| Asp35
| <cite>Yaoi2007</cite>
|-
| [[GH76]]
| none
| (α/α)6
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5agd 5agd]
| endo-α-1,6-mannanase
| ''Bacillus circulans''
| α-1,6-mannopentaose
| '''Asp125'''
| Asp124
| <cite>Thompson2015</cite>
|-
| [[GH77]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2oww 2oww]
| 4-α-glucanotransferase
| ''Thermus thermofilus''
| acarbose + 4-deoxy-α-{{Smallcaps|d}}-glucose
| '''Glu340'''
| Asp293
| <cite>Barends2007</cite>
|-
| [[GH78]]
| H
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3w5n 3w5n]
| α-{{Smallcaps|l}}-rhamnosidase
| ''Streptomyces avermitilis''
| {{Smallcaps|l}}-rhamnose
| '''Glu636'''
| Glu895
| <cite>Fujimoto2013</cite>
|-
| [[GH79]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5e9c 5e9c]
| heparanase
| ''Homo sapiens''
| heparin tetrasaccharide
| '''Glu225'''
| Glu343
| <cite>Wu2015</cite>
|-
| [[GH80]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH24''
|
|
|
|
|
|
|-
| [[GH81]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5t4g 5t4g]
| endo-β-1,3-glucanase
| ''Bacillus halodurans'' C-125
| laminarin
| '''Asp466'''
| Glu542
| <cite>Pluvinage2017</cite>
|-
| [[GH83]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH33''
|
|
|
|
|
|
|-
| [[GH84]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2chn 2chn]
| β-''N''-acetyl-glucosaminidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| NAG-thiazoline
| '''Glu242'''
| internal
| <cite>Dennis2006</cite>
|-
| [[GH85]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w92 2w92]
| endo-β-''N''-acetyl-glucosaminidase D
| ''Streptococcus pneumoniae'' TIGR4
| NAG-thiazoline
| '''Glu337'''
| internal
| <cite>Abbott2009</cite>
|-
| [[GH86]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4aw7 4aw7]
| β-porphyranase
| ''Bacteroides plebeius''
| porphyran fragment
| '''Glu152'''
| Glu279
| <cite>Hehemann_1_2012</cite>
|-
| [[GH89]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vcb 2vcb]
| α-''N''-acetyl-glucosaminidase
| ''Clostridium perfringens''
| PUGNAc
| '''Glu483'''
| Glu601
| <cite>Ficko-Blean2008</cite>
|-
| [[GH92]]
| none
| (α/α)6 and β-sandwich
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ww1 2ww1]
| α-1,2-mannosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| thiomannobioside
| '''Glu533'''
| Asp644 Asp642
| <cite>Zhu2009</cite>
|-
| [[GH93]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3a72 3a72]
| exo-arabinanase
| ''Penicillium chrysogenum''
| arabinobiose
| '''Glu246'''
| Glu174
| <cite>Sogabe2011</cite>
|-
| [[GH94]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4zli 4zli]
| cellobionic acid phosphorylase
| ''Saccharophagus degradans''
| 3-O-β-{{Smallcaps|d}}-glucopyranosyl-α-{{Smallcaps|d}}-glucopyranuronic acid
| '''Asp472'''
| phosphate
| <cite>Nam2015</cite>
|-
| [[GH95]]
| none
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ead 2ead]
| α-1,2-{{Smallcaps|l}}-fucosidase
| ''Bifidobacterium bifidum''
| Fuc-α-1,2-Gal
| '''Glu566'''
| Asn423 Asp766
| <cite>Nagae2007</cite>
|-
| [[GH97]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining + inverting
| '''''anti'''''
| [{{PDBlink}}2zq0 2zq0]
| α-glucosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| acarbose
| '''Glu532'''
| Glu508
| <cite>Kitamura2008</cite>
|-
| [[GH98]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2wmg 2wmg]
| endo-β-1,4-galactosidase
| ''Streptococcus pneumoniae''
| A-LewisY pentasaccharide
| '''Glu158'''
| Asp251 Glu301
| <cite>Higgins2009</cite>
|-
| [[GH99]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ad4 4ad4]
| endo-α-mannosidase
| ''Bacteroides xylanisolvens''
| glucose-1,3-isofagomine and α-1,2- mannobiose
| '''Glu336'''
| debated
| <cite>Thompson2012</cite>
|-
| [[GH100]]
| none
| (α/α)6 core
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5gop 5gop]
| invertase
| ''Anabaena (Nostoc) sp.'' pcc7120
| sucrose
| '''Asp188'''
| Glu414
| <cite>Xie2016</cite>
|-
| [[GH102]]
| none
| double-ψ β-barrel
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}2pi8 2pi8]
| lytic transglycosylase A
| ''Escherichia coli''
| chitohexaose
| '''Asp308'''
| none
| <cite>van_Straaten2007</cite>
|-
| [[GH103]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1d0k 1d0k]
| lytic transglycosylase SLT35
| ''Escherichia coli''
| murodipeptides
| '''Glu162'''
| internal
| <cite>van_Asselt2000</cite>
|-
| [[GH106]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5mwk 5mwk]
| α-{{Smallcaps|l}}-rhamnosidase BT_0986
| ''Bacteroides thetaiotaomicron''
| pectin heptasaccharide
| '''Glu461'''
| Glu593 or Glu561
| <cite>Ndeh2017</cite>
|-
| [[GH107]]
| R
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| ''predicted syn by clan''
| ''see at GH29''
|
|
|
|
|
|
|-
| [[GH113]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4cd8 4cd8]
| β-mannanase
| ''Alicyclobacillus acidocaldarius''
| mannobioimidazole
| '''Glu151'''
| Glu231
| <cite>Williams2014</cite>
|-
| [[GH116]]
| O
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at GH52''
|
|
|
|
|
|
|-
| [[GH117]]
| none
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}4ak7 4ak7]
| α-1,3-3,6-anhydro-{{Smallcaps|l}}-galactosidase
| ''Bacteroides plebeius''
| neoagarobiose
| '''His302'''
| Asp90
| <cite>Hehemann_2_2012</cite>
|-
| [[GH120]]
| none
| parallel β-helix and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3vsv 3vsv]
| β-xylosidase XylC
| ''Thermoanaerobacterium saccharolyticum'' JW/SL-YS485
| {{Smallcaps|d}}-xylose
| '''Glu405'''
| Asp382
| <cite>Huang2012</cite>
|-
| [[GH123]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5fr0 5fr0]
| exo-β-N-acetyl-galactosaminidase
| ''Clostridium perfringens''
| ''N''-difluoroacetyl-{{Smallcaps|d}}-galactosamine
| '''Glu345'''
| internal
| <cite>Noach2016</cite>
|-
| [[GH125]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5m7y 5m7y]
| exo-α-1,6-mannosidase
| ''Clostridium perfringens''
| 1,6-α-mannotriose
| '''Asp220'''
| Glu393
| <cite>Alonso-Gil2016</cite>
|-
| [[GH127]]
| P
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3wrg 3wrg]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bifidobacterium longum''
| {{Smallcaps|l}}-arabinose
| '''Glu322'''
| Cys417
| <cite>Huang2014</cite>
|-
| [[GH128]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH1''
|
|
|
|
|
|
|-
| [[GH130]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5b0s 5b0s]
| β-1,2-mannobiose phosphorylase
| ''Listeria innocua''
| β-1,2-mannotriose
| '''Asp141''' relay
| phosphate
| <cite>Tsuda2015</cite>
|-
| [[GH134]]
| none
| β + α
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5jug 5jug]
| β-mannanase
| ''Streptomyces sp.''
| mannopentaose
| '''Glu45'''
| Asp57
| <cite>Jin2016</cite>
|-
| [[GH137]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|l}}
| unknown
| '''''anti'''''
| [{{PDBlink}}5mui 5mui]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0996
| ''Bacteroides thetaiotaomicron''
| pectin oligosaccharide
| '''Glu240'''
| Glu159
| <cite>Ndeh2017</cite>
|-
| [[GH146]]
| P
| (α/α)6
| beta-{{Smallcaps|l}}
| retaining
| ''predicted anti by clan''
| ''see at GH127''
|
|
|
|
|
|
|-
| [[GH147]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH148]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at e.g. GH1''
|
|
|
|
|
|
|-
| [[GH149]]
| Q
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH94''
|
|
|
|
|
|
|-
| [http://www.cazy.org/GH0.html n.c.*]
| none
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2vjj 2vjj]
| endo-α-N-acetylglucosaminidase
| Bacteriophage HK620
| O18A1 O-antigen hexasaccharide
| '''Asp339'''
| Glu372
| <cite>Barbirz2008</cite>
|}
<nowiki>*</nowiki> n.c.: Found among the collection of [http://www.cazy.org/GH0.html non-classified GH sequences in the CAZy Database].

== References ==

<biblio>
# HeightmanVasella1999 Heightman TD and Vasella AT. ''Recent Insights into Inhibition, Structure, and Mechanism of Configuration-Retaining Glycosidases.'' Angew Chem Int Ed. 1999 38(6):750-770. [http://www3.interscience.wiley.com/journal/55000581/abstract Article online].
# Nerinckx2005 pmid=15642336
# Wu2012 pmid=23137336
# Perez1978 Pérez S and Marchessault RH. ''The exo-anomeric effect: experimental evidence from crystal structures.'' Carbohydr res. 1978 65:114-120. [http://dx.doi.org/10.1016/S0008-6215(00)84218-4 DOI:10.1016/S0008-6215(00)84218-4]
# Cramer1997 Cramer CJ, Truhlar DG, and French AD. ''Exo-anomeric effects on energies and geometries of different conformations of glucose and related systems in the gas phase and aqueous solution.'' Carbohydr res. 1997 298:1-14. [http://dx.doi.org/10.1016/S0008-6215(96)00297-2 DOI:10.1016/S0008-6215(96)00297-2]
# Johnson2009 pmid=19733839
# Alonso2016 pmid=26889578
# Gloster2006 pmid=17002288
# van_Bueren2009 pmid=18976664
# Hrmova2001 pmid=11709165
# Varrot2003 pmid=12595701
# Zhou1999 pmid=10508787
# Sulzenbacher1999 pmid=10200171
# Urbanikova2011 pmid=21501386
# Guerin2002 pmid=11884144
# Schubot2004 pmid=14756552
# Suzuki2009 pmid=19279191
# Wan2014 pmid=24419374
# Sandgren2004 pmid=15364577
# Uitdehaag1999 pmid=10331869
# Miyake2003 pmid=12741813
# Harris1993 pmid=8431441
# Allouch2004 pmid=15062085
# Papanikolau2001 pmid=11560481
# Prag2000 pmid=10884356
# Vocadlo2001 pmid=11518970
# Karlsen1996 pmid=15299731
# Baldwin1993 pmid=8259514
# Cartmell2008 pmid=18799462
# Fernandez-Leiro2010 pmid=20592022
# Abbott2007 pmid=17397864
# Sakurama2012 pmid=22451675
# Sim2008 pmid=18036614
# Verhaest2007 pmid=17335500
# Amaya2004 pmid=15130470
# Zhu2012 pmid=23015718
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# Merceron2012 pmid=23012371
# Gibson2007 pmid=17455176
# Shah2008 pmid=18599462
# Czjzek2005 pmid=16212978
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# Lyu2014 pmid=24766439
# Karaveg2005 pmid=15713668
# Nerinckx2008 pmid=18619586
# Pluvinage2013 pmid=23921382
# Hoevel2003 pmid=14517232
# Espina2014 pmid=24816105
# Le_Nours2009 pmid=19089956
# Miyanaga2004 pmid=15292273
# Bianchetti2015 pmid=25752603
# Markovic-Housley2000 pmid=11080624
# Imamura2003 pmid=12618437
# Hill2013 pmid=24297913
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# Touhara2014 pmid=24828502
# Suzuki2016 pmid=26494689
# Golan2004 pmid=14573597
# Meng2003 pmid=14517548
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# Hurtado-Gerrero2009 pmid=19097997
# Yaoi2007 pmid=17498741
# Thompson2015 pmid=25772148
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# Zhu2009 pmid=20081828
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# Higgins2009 pmid=19608744
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# Ndeh2017 pmid=28329766
# Jin2016 Jin Y, Petricevic M, John A, Raich L, Jenkins H, Portela De Souza L, Cuskin F, Gilbert HJ, Rovira C, Goddard-Borger ED, Williams SJ, and Davies GJ. ''A β-Mannanase with a Lysozyme-like Fold and a Novel Molecular Catalytic Mechanism.'' ACS Cent Sci. 2016 Nov [http://dx.doi.org/10.1021/acscentsci.6b00232 DOI:10.1021/acscentsci.6b00232]
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</biblio>

[[Category:Definitions and explanations]]

Syn/anti lateral protonation

2018-01-07T23:58:38Z

Wim Nerinckx:

{{CuratorApproved}}
* [[Author]]: ^^^Wim Nerinckx^^^
* [[Responsible Curator]]: ^^^Spencer Williams^^^

----

== Overview ==

This page provides a table that summarizes the spatial positioning of the catalytic [[general acid]] residue in the active sites of [[glycoside hydrolase]]s, relative to the substrate. The table below updates those found in the seminal paper on this concept by Heightman and Vasella <cite>HeightmanVasella1999</cite>, and a following paper by Nerinckx ''et al.'' <cite>Nerinckx2005</cite>.

== Background ==

The ''"not from above, but from the side"'' concept of semi-lateral glycosidic oxygen [[General_acid/base|protonation]] by [[glycoside hydrolase]]s was introduced by Heightman and Vasella <cite>HeightmanVasella1999</cite>. It was originally only described for [[Anomeric centre (alpha and beta)|beta]]-equatorial [[glycoside hydrolase]]s, but appears to be equally applicable to enzymes acting on an [[Anomeric centre (alpha and beta)|alpha]]-axial glycosidic bond <cite>Nerinckx2005</cite>. When dividing [[Sub-site nomenclature|subsite -1]] into half-spaces by a plane defined by the glycosidic oxygen and C1' and H1' of the –1 glycoside, many ligand-complexed structures reveal that the [[General_acid/base|proton donor]] is positioned either in the ''syn'' half-space (near the ring-oxygen of the –1 glycoside), or in the ''anti'' half-space (on the opposite side of the ring-oxygen). Members of the same GH [[Families|family]] appear to share a common ''syn'' or ''anti'' [[General_acid/base|protonator]] arrangement and further, this specificity appears to be preserved within [[Clans|Clans]] of [[Families|families]]. This page's compilation of [[Sub-site nomenclature|subsite -1]] occupied complexes shows that about 70% of all GH [[Families|families]] are ''anti'' [[General_acid/base|protonators]].

Closer inspection of crystal structures of [[Sub-site nomenclature|–1/+1 subsite]]-spanning substrates, or substrate-analogue ligands, in complex with enzymes reveals a further intriguing corollary <cite>Nerinckx2005 Wu2012</cite>. In substrate-bound complexes with ''anti'' [[General_acid/base|protonating]] GH enzymes, the scissile [[Anomeric centre (alpha and beta)|anomeric bond]] (often studied using the thio-analogue) shows a dihedral angle φ (O5'-C1'-[O,S]x-Cx) that is in the lowest-energy synclinal (gauche) conformation. The rationale for this is that a minus synclinal dihedral angle φ for an equatorial glycosidic bond, or plus synclinal for an axial glycosidic bond <cite>Perez1978</cite>, allows for hyperconjugative overlap of the C1'-O5' antibonding orbital with an antiperiplanar-oriented lone pair orbital lobe of the glycosidic oxygen, thereby creating partial double bond character and stabilization of the glycosidic bond by 4–5 kcal/mol; this ground-state stabilizing phenomenon is known as the ‘exo-anomeric effect’ <cite>Cramer1997 Johnson2009 Alonso2016</cite>. ''Anti'' [[General_acid/base|protonation]] occurs on the glycosidic oxygen’s antiperiplanar lone pair, thereby removing the stabilizing exo-anomeric effect. This suggests that ''anti'' [[General_acid/base|protonation]] is an enzymic approach for lowering the activation barrier leading to the [[Transition state|transition state]] (Figure 1 centre).

''Syn'' [[General_acid/base|protonating]] [[glycoside hydrolase]]s apparently make use of a different approach <cite>Nerinckx2005 Wu2012</cite>. In many [[Sub-site nomenclature|–1/+1 subsite]]-spanning ligand complexes, the dihedral angle φ of the scissile anomeric bond has been rotated away from its lowest-energy synclinal position: clockwise to minus-anticlinal or antiperiplanar for beta-equatorial; counterclockwise to plus-anticlinal or antiperiplanar for alpha-axial [[Anomeric centre (alpha and beta)|anomeric bonds]]. This removes the hyperconjugative overlap and thus also the stabilizing exo-anomeric effect. And because of this rotation, a lone pair of the glycosidic oxygen is directed into the ''syn'' half-space, allowing it to be protonated by the ''syn''-positioned [[General_acid/base|proton donor]] (Figure 1 right).

[[File:Syn_anti.jpg|800px|thumb|center|Figure 1. Newman projections, with the glycosidic oxygen as proximal atom and the anomeric carbon as distal atom, showing ''anti'' (centre) versus ''syn'' (right) semi-lateral [[General_acid/base|protonation]] in beta-equatorial (top) and alpha-axial (bottom) [[glycoside hydrolase]]s. The indicated φ is the dihedral angle for O5'-C1'-O4-C4.]]

== Table of ''syn/anti'' protonation examples ==

This table contains only one example per GH [[Families|family]] of a ligand-complexed protein structure where the ''syn'' or ''anti'' positioning of the [[General_acid/base|proton donor]] can be clearly observed; other examples may be available on a [[Families|family-by-family]] basis. The reader is thus advised to consult the [http://www.cazy.org/fam/acc_GH.html#table CAZy database] for a current, comprehensive list of CAZyme structures. Where available, the selected examples are Michaelis-type complexes with the ligand spanning the [[Sub-site nomenclature|-1/+1 subsites]], since these have an intact glycosidic or thioglycosidic bond, or are ''N''-analogs of the substrate (''e.g.'' acarbose). In some examples, the [[General_acid/base|proton donor]] has been mutated (''e.g.'', to the corresponding amide or to an alanine), and in those cases one may wish to look at a superposition of the given PDB example with the structure of the native enzyme. If a Michaelis-type complex is not yet available, the second and third example choices, respectively, are trapped glycosyl-enzyme [[intermediate]]s and product complexes where [[Sub-site nomenclature|subsite -1]] is occupied.

''Please also be aware that this is a large table with many data. Please contact the page Author or Responsible Curator with corrections.''

=== Table ===
This table can be re-sorted by clicking on the icons in the header (''javascript must be turned on in your browser''). To reset the page to be sorted by GH family, click the ''View'' tab at the very top of the page.

{| {{Prettytable}} class="sortable"
|- valign="top"
! '''Family'''
! '''Clan'''
! '''Structure fold '''
! '''Anomeric specificity'''
! '''Mechanism'''
! '''''Syn/anti'' protonator'''
! '''Example PDB ID'''
! '''Enzyme'''
! '''Organism'''
! '''Ligand'''
! '''General acid'''
! '''Nucleophile or General base'''
! '''Reference'''
|-
| [[GH1]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2cer 2cer]
| β-glycosidase S
| ''Sulfolobus solfataricus'' P2
| phenethyl glucoimidazole
| '''Glu206'''
| Glu387
| <cite>Gloster2006</cite>
|-
| [[GH2]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vzu 2vzu]
| exo-β-glucosaminidase
| ''Amicolatopsis orientalis''
| PNP-β-{{Smallcaps|d}}-glucosamine
| '''Glu469'''
| Glu541
| <cite>van_Bueren2009</cite>
|-
| [[GH3]]
| none
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1iex 1iex]
| exo-1,3-1,4-glucanase
| ''Hordeum vulgare''
| thiocellobiose
| '''Glu491'''
| Asp285
| <cite>Hrmova2001</cite>
|-
| [[GH5]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1h2j 1h2j]
| endo-β-1,4-glucanase
| ''Bacillus agaradhaerens''
| 2',4'-DNP-2-F-cellobioside
| '''Glu129'''
| Glu228
| <cite>Varrot2003</cite>
|-
| [[GH6]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1qjw 1qjw]
| cellobiohydrolase 2
| ''Hypocrea jecorina''
| (Glc)2-S-(Glc)2
| '''Asp221'''
| debated
| <cite>Zhou1999</cite>
|-
| [[GH7]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1ovw 1ovw]
| endo-1,4-glucanase
| ''Fusarium oxysporum''
| thio-(Glc)5
| '''Glu202'''
| Glu197
| <cite>Sulzenbacher1999</cite>
|-
| [[GH8]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1kwf 1kwf]
| endo-1,4-glucanase
| ''Clostridium thermocellum''
| cellopentaose
| '''Glu95'''
| Asp278
| <cite>Guerin2002</cite>
|-
| [[GH9]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1rq5 1rq5]
| cellobiohydrolase
| ''Clostridium thermocellum''
| cellotetraose
| '''Glu795'''
| Asp383
| <cite>Schubot2004</cite>
|-
| [[GH10]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2d24 2d24]
| β-1,4-xylanase
| ''Streptomyces olivaceoviridis'' E-86
| xylopentaose
| '''Glu128'''
| Glu236
| <cite>Suzuki2009</cite>
|-
| [[GH11]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}4hk8 4hk8]
| endo-β-1,4-xylanase
| ''Hypocrea jecorina''
| xylohexaose
| '''Glu177'''
| Glu86
| <cite>Wan2014</cite>
|-
| [[GH12]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1w2u 1w2u]
| endoglucanase
| ''Humicola grisea''
| thiocellotetraose
| '''Glu205'''
| Glu120
| <cite>Sandgren2004</cite>
|-
| [[GH13]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1cxk 1cxk]
| β-cyclodextrin glucanotransferase
| ''Bacillus circulans''
| maltononaose
| '''Glu257'''
| Asp229
| <cite>Uitdehaag1999</cite>
|-
| [[GH14]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1itc 1itc]
| β-amylase
| ''Bacillus cereus''
| maltopentaose
| '''Glu172'''
| Glu367
| <cite>Miyake2003</cite>
|-
| [[GH15]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1dog 1dog]
| glucoamylase
| ''Aspergillus awamori''
| 1-deoxynojirimycin
| '''Glu179'''
| Glu400
| <cite>Harris1993</cite>
|-
| [[GH16]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1urx 1urx]
| β-agarase A
| ''Zobellia galactanivorans''
| oligoagarose
| '''Glu152'''
| Glu147
| <cite>Allouch2004</cite>
|-
| [[GH17]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH1''
|
|
|
|
|
|
|-
| [[GH18]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1ffr 1ffr]
| chitinase A
| ''Serratia marcescens''
| (NAG)6
| '''Glu315'''
| internal
| <cite>Papanikolau2001</cite>
|-
| [[GH19]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}3wh1 3wh1]
| chitinase
| ''Bryum coronatum''
| (GlcNAc)4
| '''Glu61'''
| Glu70
| <cite>Ohnuma2014</cite>
|-
| [[GH20]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1c7s 1c7s]
| chitobiase
| ''Serratia marcescens''
| chitobiose
| '''Glu540'''
| internal
| <cite>Prag2000</cite>
|-
| [[GH22]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1h6m 1h6m]
| lysozyme C
| ''Gallus gallus''
| Chit-2-F-chitosyl
| '''Glu35'''
| Asp52
| <cite>Vocadlo2001</cite>
|-
| [[GH23]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1lsp 1lsp]
| lysozyme G
| ''Cygnus atratus''
| Bulgecin A
| '''Glu73'''
| internal
| <cite>Karlsen1996</cite>
|-
| [[GH24]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}148l 148l]
| lysozyme E
| Bacteriophage T4
| chitobiosyl
| '''Glu11'''
| Glu26
| <cite>Baldwin1993</cite>
|-
| [[GH26]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vx6 2vx6]
| exo-β-mannanase
| ''Cellvibrio japonicus'' Ueda107
| Gal1Man4
| '''Glu221'''
| Glu338
| <cite>Cartmell2008</cite>
|-
| [[GH27]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}} / beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3lrm 3lrm]
| α-galactosidase
| ''Saccharomyces cerevisiae''
| raffinose
| '''Asp209'''
| Asp141
| <cite>Fernandez-Leiro2010</cite>
|-
| [[GH28]]
| N
| β-helix
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}2uvf 2uvf]
| exo-polygalacturonosidase
| ''Yersinia enterocolitica'' ATCC9610D
| digalacturonic acid
| '''Asp402'''
| Asp381 Asp403
| <cite>Abbott2007</cite>
|-
| [[GH29]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| '''''syn'''''
| [{{PDBlink}}3uet 3uet]
| α-1,3/4-fucosidase
| ''Bifidobacterium longum'' subsp. infantis
| lacto-''N''-fucopentaose II
| '''Glu217'''
| Asp172
| <cite>Sakurama2012</cite>
|-
| [[GH30]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2y24 2y24]
| glucurono-xylanase
| ''Dickea chrysanthemi'' D1
| glucuronoxylan tetrasaccharide
| '''Glu163'''
| Glu253
| <cite>Urbanikova2011</cite>
|-
| [[GH31]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2qmj 2qmj]
| maltase-glucoamylase
| ''Homo sapiens''
| acarbose
| '''Asp542'''
| Asp443
| <cite>Sim2008</cite>
|-
| [[GH32]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2add 2add]
| fructan β-(2,1)-fructosidase
| ''Cichorium intybus''
| sucrose
| '''Glu201'''
| Asp22
| <cite>Verhaest2007</cite>
|-
| [[GH33]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1s0i 1s0i]
| transsialidase
| ''Trypanosoma cruzi''
| sialyllactose
| '''Asp59'''
| Tyr342
| <cite>Amaya2004</cite>
|-
| [[GH34]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzw 4gzw]
| N2 neuraminidase
| ''Influenza'' A Tanzania/205/2010 H3N2
| α-{{Smallcaps|d}}-Neup5Ac-(2,3)-β-{{Smallcaps|d}}-Galp-(1,4)-β-{{Smallcaps|d}}-GlcpNAc
| '''Asp151'''
| Tyr406
| <cite>Zhu2012</cite>
|-
| [[GH35]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3ogv 3ogv]
| β-galactosidase
| ''Hypocrea jecorina''
| 2-phenylethyl 1-thio-β-{{Smallcaps|d}}-galactopyranoside
| '''Glu200'''
| Glu298
| <cite>Maksimainen2011</cite>
|-
| [[GH36]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4fns 4fns]
| β-galactosidase
| ''Geobacillus stearothermophilus''
| 1-deoxy galactonojirimycin
| '''Asp584'''
| Asp478
| <cite>Merceron2012</cite>
|-
| [[GH37]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2jf4 2jf4]
| trehalase
| ''Escherichia coli''
| validoxylamine
| '''Asp312'''
| Glu496
| <cite>Gibson2007</cite>
|-
| [[GH38]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3czn 3czn]
| Golgi α-mannosidase II
| ''Drosophila melanogaster''
| GlcNAcMan(5)GlcNAc(2)
| '''Asp341'''
| Asp204
| <cite>Shah2008</cite>
|-
| [[GH39]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2bfg 2bfg]
| β-xylosidase
| ''Geobacillus stearothermophilus''
| 2,5-dinitrophenyl-β-{{Smallcaps|d}}-xyloside
| '''Glu160'''
| Glu278
| <cite>Czjzek2005</cite>
|-
| [[GH42]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ucf 4ucf]
| β-galactosidase
| ''Bifidobacterium bifidum''
| {{Smallcaps|d}}-galactose
| '''Glu161'''
| Glu320
| <cite>Godoy2016</cite>
|-
| [[GH43]]
| F
| 5-fold β-propeller
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3akh 3akh]
| exo-1,5-α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces avermitilis''
| α-1,5-arabinofuranotriose
| '''Glu196'''
| Asp220
| <cite>Fujimoto2010</cite>
|-
| [[GH44]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2eqd 2eqd]
| endoglucanase
| ''Clostridium thermocellum''
| cellooctaose
| '''Glu186'''
| Glu359
| <cite>Kitago2007</cite>
|-
| [[GH45]]
| none
| 6-stranded β-barrel
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4eng 4eng]
| endo-1,4-glucanase
| ''Humicola insolens''
| cellohexaose
| '''Asp121'''
| Asp10
| <cite>Davies1996</cite>
|-
| [[GH46]]
| I
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4olt 4olt]
| chitosanase
| ''Microbacterium sp.'' OU01
| hexa-glucosamine
| '''Glu25'''
| Asp43
| <cite>Lyu2014</cite>
|-
| [[GH47]]
| none
| (α/α)7
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1x9d 1x9d]
| α-mannosidase I
| ''Homo sapiens''
| Me-2-S-(α-Man)-2-thio-α-Man
| '''Asp463'''
| Glu599
| <cite>Karaveg2005</cite>, <cite>Nerinckx2008</cite>
|-
| [[GH48]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH8''
|
|
|
|
|
|
|-
| [[GH49]]
| N
| β-helix
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH28''
|
|
|
|
|
|
|-
| [[GH50]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4bq5 4bq5]
| exo-β-agarase
| ''Saccharophagus degradans''
| neoagarotetraose
| '''Glu535'''
| Glu695
| <cite>Pluvinage2013</cite>
|-
| [[GH51]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1qw9 1qw9]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Geobacillus stearothermophilus''
| PNP-{{Smallcaps|l}}-arabinofuranoside
| '''Glu175'''
| Glu294
| <cite>Hoevel2003</cite>
|-
| [[GH52]]
| O
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4c1p 4c1p]
| β-xylosidase
| ''Geobacillus thermoglucosidasius''
| xylobiose
| '''Asp517'''
| Glu537
| <cite>Espina2014</cite>
|-
| [[GH53]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2ccr 2ccr]
| β-1,4-galactanase
| ''Bacillus licheniformis''
| galactotriose
| '''Glu165'''
| Glu263
| <cite>Le_Nours2009</cite>
|-
| [[GH54]]
| none
| β-sandwich
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1wd4 1wd4]
| α-{{Smallcaps|l}}-arabinofuranosidase B
| ''Aspergillus kawachii''
| {{Smallcaps|l}}-arabinofuranose
| '''Asp297'''
| Glu221
| <cite>Miyanaga2004</cite>
|-
| [[GH55]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4tz5 4tz5]
| exo-β-1,3-glucanase
| ''Streptomyces sp.'' SirexAA-E
| laminarihexaose
| '''Glu502'''
| unknown
| <cite>Bianchetti2015</cite>
|-
| [[GH56]]
| none
| (β/α)7
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1fcv 1fcv]
| hyaluronidase
| ''Apis mellifera''
| (hyaluron.)4
| '''Glu113'''
| internal
| <cite>Markovic-Housley2000</cite>
|-
| [[GH57]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1k1y 1k1y]
| glucanotransferase
| ''Thermococcus litoralis''
| acarbose
| '''Asp214'''
| Glu123
| <cite>Imamura2003</cite>
|-
| [[GH59]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ccc 4ccc]
| β-galactocerebrosidase
| ''Mus musculus''
| PNP-β-{{Smallcaps|d}}-galactoside
| '''Glu182'''
| Glu258
| <cite>Hill2013</cite>
|-
| [[GH62]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| unknown
| ''predicted anti by clan''
| ''see at GH43''
|
|
|
|
|
|
|-
| [[GH63]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5ca3 5ca3]
| α-glucosidase
| ''Escherichia coli''
| glucose and lactose
| '''Asp501'''
| Glu727
| <cite>Miyazaki2016</cite>
|-
| [[GH65]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}4ktr 4ktr]
| 2-O-α-glucosylglycerol phosphorylase
| ''Bacillus selenitireducens''
| isofagomine
| '''Glu475'''
| phosphate
| <cite>Touhara2014</cite>
|-
| [[GH66]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5axh 5axh]
| dextranase
| ''Thermoanaerobacter pseudethanolicus''
| isomaltohexaose
| '''Glu374'''
| Asp312
| <cite>Suzuki2016</cite>
|-
| [[GH67]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1l8n 1l8n]
| α-glucuronidase
| ''Geobacillus stearothermophilus''
| 4-O-methyl-{{Smallcaps|d}}-glucuronic acid and xylotriose
| '''Glu286'''
| Asp364 Glu392
| <cite>Golan2004</cite>
|-
| [[GH68]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1pt2 1pt2]
| levansucrase
| ''Bacillus subtilis''
| sucrose
| '''Glu342'''
| Asp86
| <cite>Meng2003</cite>
|-
| [[GH70]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3aic 3aic]
| glucansucrase
| ''Streptococcus mutans''
| α-acarbose
| '''Glu515'''
| Asp477
| <cite>Ito2011</cite>
|-
| [[GH72]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w62 2w62]
| β-1,3-glucanotransferase
| ''Saccharomyces cerevisiae'' S288C
| laminaripentaose
| '''Glu176'''
| Glu275
| <cite>Hurtado-Gerrero2009</cite>
|-
| [[GH74]]
| none
| 7-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}2ebs 2ebs]
| cellobiohydrolase (OXG-RCBH)
| ''Geotrichum sp.'' m128
| xyloglucan heptasaccharide
| '''Asp465'''
| Asp35
| <cite>Yaoi2007</cite>
|-
| [[GH76]]
| none
| (α/α)6
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5agd 5agd]
| endo-α-1,6-mannanase
| ''Bacillus circulans''
| α-1,6-mannopentaose
| '''Asp125'''
| Asp124
| <cite>Thompson2015</cite>
|-
| [[GH77]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2oww 2oww]
| 4-α-glucanotransferase
| ''Thermus thermofilus''
| acarbose + 4-deoxy-α-{{Smallcaps|d}}-glucose
| '''Glu340'''
| Asp293
| <cite>Barends2007</cite>
|-
| [[GH78]]
| H
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3w5n 3w5n]
| α-{{Smallcaps|l}}-rhamnosidase
| ''Streptomyces avermitilis''
| {{Smallcaps|l}}-rhamnose
| '''Glu636'''
| Glu895
| <cite>Fujimoto2013</cite>
|-
| [[GH79]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5e9c 5e9c]
| heparanase
| ''Homo sapiens''
| heparin tetrasaccharide
| '''Glu225'''
| Glu343
| <cite>Wu2015</cite>
|-
| [[GH80]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH24''
|
|
|
|
|
|
|-
| [[GH81]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5t4g 5t4g]
| endo-β-1,3-glucanase
| ''Bacillus halodurans'' C-125
| laminarin
| '''Asp466'''
| Glu542
| <cite>Pluvinage2017</cite>
|-
| [[GH83]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH33''
|
|
|
|
|
|
|-
| [[GH84]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2chn 2chn]
| β-''N''-acetyl-glucosaminidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| NAG-thiazoline
| '''Glu242'''
| internal
| <cite>Dennis2006</cite>
|-
| [[GH85]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w92 2w92]
| endo-β-''N''-acetyl-glucosaminidase D
| ''Streptococcus pneumoniae'' TIGR4
| NAG-thiazoline
| '''Glu337'''
| internal
| <cite>Abbott2009</cite>
|-
| [[GH86]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4aw7 4aw7]
| β-porphyranase
| ''Bacteroides plebeius''
| porphyran fragment
| '''Glu152'''
| Glu279
| <cite>Hehemann_1_2012</cite>
|-
| [[GH89]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vcb 2vcb]
| α-''N''-acetyl-glucosaminidase
| ''Clostridium perfringens''
| PUGNAc
| '''Glu483'''
| Glu601
| <cite>Ficko-Blean2008</cite>
|-
| [[GH92]]
| none
| (α/α)6 and β-sandw.
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ww1 2ww1]
| α-1,2-mannosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| thiomannobioside
| '''Glu533'''
| Asp644 Asp642
| <cite>Zhu2009</cite>
|-
| [[GH93]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3a72 3a72]
| exo-arabinanase
| ''Penicillium chrysogenum''
| arabinobiose
| '''Glu246'''
| Glu174
| <cite>Sogabe2011</cite>
|-
| [[GH94]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4zli 4zli]
| cellobionic acid phosphorylase
| ''Saccharophagus degradans''
| 3-O-β-{{Smallcaps|d}}-glucopyranosyl-α-{{Smallcaps|d}}-glucopyranuronic acid
| '''Asp472'''
| phosphate
| <cite>Nam2015</cite>
|-
| [[GH95]]
| none
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ead 2ead]
| α-1,2-{{Smallcaps|l}}-fucosidase
| ''Bifidobacterium bifidum''
| Fuc-α-1,2-Gal
| '''Glu566'''
| Asn423 Asp766
| <cite>Nagae2007</cite>
|-
| [[GH97]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining + inverting
| '''''anti'''''
| [{{PDBlink}}2zq0 2zq0]
| α-glucosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| acarbose
| '''Glu532'''
| Glu508
| <cite>Kitamura2008</cite>
|-
| [[GH98]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2wmg 2wmg]
| endo-β-1,4-galactosidase
| ''Streptococcus pneumoniae''
| A-LewisY pentasaccharide
| '''Glu158'''
| Asp251 Glu301
| <cite>Higgins2009</cite>
|-
| [[GH99]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ad4 4ad4]
| endo-α-mannosidase
| ''Bacteroides xylanisolvens''
| glucose-1,3-isofagomine and α-1,2- mannobiose
| '''Glu336'''
| debated
| <cite>Thompson2012</cite>
|-
| [[GH100]]
| none
| (α/α)6 core
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5gop 5gop]
| invertase
| ''Anabaena (Nostoc) sp.'' pcc7120
| sucrose
| '''Asp188'''
| Glu414
| <cite>Xie2016</cite>
|-
| [[GH102]]
| none
| double-ψ β-barrel
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}2pi8 2pi8]
| lytic transglycosylase A
| ''Escherichia coli''
| chitohexaose
| '''Asp308'''
| none
| <cite>van_Straaten2007</cite>
|-
| [[GH103]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1d0k 1d0k]
| lytic transglycosylase SLT35
| ''Escherichia coli''
| murodipeptides
| '''Glu162'''
| internal
| <cite>van_Asselt2000</cite>
|-
| [[GH106]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5mwk 5mwk]
| α-{{Smallcaps|l}}-rhamnosidase BT_0986
| ''Bacteroides thetaiotaomicron''
| pectin heptasaccharide
| '''Glu461'''
| Glu593 or Glu561
| <cite>Ndeh2017</cite>
|-
| [[GH113]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4cd8 4cd8]
| β-mannanase
| ''Alicyclobacillus acidocaldarius''
| mannobioimidazole
| '''Glu151'''
| Glu231
| <cite>Williams2014</cite>
|-
| [[GH116]]
| O
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at GH52''
|
|
|
|
|
|
|-
| [[GH117]]
| none
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}4ak7 4ak7]
| α-1,3-3,6-anhydro-{{Smallcaps|l}}-galactosidase
| ''Bacteroides plebeius''
| neoagarobiose
| '''His302'''
| Asp90
| <cite>Hehemann_2_2012</cite>
|-
| [[GH120]]
| none
| parallel β-helix and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3vsv 3vsv]
| β-xylosidase XylC
| ''Thermoanaerobacterium saccharolyticum'' JW/SL-YS485
| {{Smallcaps|d}}-xylose
| '''Glu405'''
| Asp382
| <cite>Huang2012</cite>
|-
| [[GH123]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5fr0 5fr0]
| exo-β-N-acetyl-galactosaminidase
| ''Clostridium perfringens''
| ''N''-difluoroacetyl-{{Smallcaps|d}}-galactosamine
| '''Glu345'''
| internal
| <cite>Noach2016</cite>
|-
| [[GH125]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5m7y 5m7y]
| exo-α-1,6-mannosidase
| ''Clostridium perfringens''
| 1,6-α-mannotriose
| '''Asp220'''
| Glu393
| <cite>Alonso-Gil2016</cite>
|-
| [[GH127]]
| none
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3wrg 3wrg]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bifidobacterium longum''
| {{Smallcaps|l}}-arabinose
| '''Glu322'''
| Cys417
| <cite>Huang2014</cite>
|-
| [[GH128]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH1''
|
|
|
|
|
|
|-
| [[GH130]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5b0s 5b0s]
| β-1,2-mannobiose phosphorylase
| ''Listeria innocua''
| β-1,2-mannotriose
| '''Asp141''' relay
| phosphate
| <cite>Tsuda2015</cite>
|-
| [[GH134]]
| none
| β + α
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5jug 5jug]
| β-mannanase
| ''Streptomyces sp.''
| mannopentaose
| '''Glu45'''
| Asp57
| <cite>Jin2016</cite>
|-
| [[GH137]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|l}}
| unknown
| '''''anti'''''
| [{{PDBlink}}5mui 5mui]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0996
| ''Bacteroides thetaiotaomicron''
| pectin oligosaccharide
| '''Glu240'''
| Glu159
| <cite>Ndeh2017</cite>
|-
| [[N. C.]]
| N. C.
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2vjj 2vjj]
| endo-α-N-acetylglucosaminidase
| Bacteriophage HK620
| O18A1 O-antigen hexasaccharide
| '''Asp339'''
| Glu372
| <cite>Barbirz2008</cite>
|}

== References ==

<biblio>
# HeightmanVasella1999 Heightman TD and Vasella AT. ''Recent Insights into Inhibition, Structure, and Mechanism of Configuration-Retaining Glycosidases.'' Angew Chem Int Ed. 1999 38(6):750-770. [http://www3.interscience.wiley.com/journal/55000581/abstract Article online].
# Nerinckx2005 pmid=15642336
# Wu2012 pmid=23137336
# Perez1978 Pérez S and Marchessault RH. ''The exo-anomeric effect: experimental evidence from crystal structures.'' Carbohydr res. 1978 65:114-120. [http://dx.doi.org/10.1016/S0008-6215(00)84218-4 DOI:10.1016/S0008-6215(00)84218-4]
# Cramer1997 Cramer CJ, Truhlar DG, and French AD. ''Exo-anomeric effects on energies and geometries of different conformations of glucose and related systems in the gas phase and aqueous solution.'' Carbohydr res. 1997 298:1-14. [http://dx.doi.org/10.1016/S0008-6215(96)00297-2 DOI:10.1016/S0008-6215(96)00297-2]
# Johnson2009 pmid=19733839
# Alonso2016 pmid=26889578
# Gloster2006 pmid=17002288
# van_Bueren2009 pmid=18976664
# Hrmova2001 pmid=11709165
# Varrot2003 pmid=12595701
# Zhou1999 pmid=10508787
# Sulzenbacher1999 pmid=10200171
# Urbanikova2011 pmid=21501386
# Guerin2002 pmid=11884144
# Schubot2004 pmid=14756552
# Suzuki2009 pmid=19279191
# Wan2014 pmid=24419374
# Sandgren2004 pmid=15364577
# Uitdehaag1999 pmid=10331869
# Miyake2003 pmid=12741813
# Harris1993 pmid=8431441
# Allouch2004 pmid=15062085
# Papanikolau2001 pmid=11560481
# Prag2000 pmid=10884356
# Vocadlo2001 pmid=11518970
# Karlsen1996 pmid=15299731
# Baldwin1993 pmid=8259514
# Cartmell2008 pmid=18799462
# Fernandez-Leiro2010 pmid=20592022
# Abbott2007 pmid=17397864
# Sakurama2012 pmid=22451675
# Sim2008 pmid=18036614
# Verhaest2007 pmid=17335500
# Amaya2004 pmid=15130470
# Zhu2012 pmid=23015718
# Maksimainen2011 pmid=21130883
# Merceron2012 pmid=23012371
# Gibson2007 pmid=17455176
# Shah2008 pmid=18599462
# Czjzek2005 pmid=16212978
# Godoy2016 pmid=27685756
# Fujimoto2010 pmid=20739278
# Kitago2007 pmid=17905739
# Davies1996 pmid=15299721
# Lyu2014 pmid=24766439
# Karaveg2005 pmid=15713668
# Nerinckx2008 pmid=18619586
# Pluvinage2013 pmid=23921382
# Hoevel2003 pmid=14517232
# Espina2014 pmid=24816105
# Le_Nours2009 pmid=19089956
# Miyanaga2004 pmid=15292273
# Bianchetti2015 pmid=25752603
# Markovic-Housley2000 pmid=11080624
# Imamura2003 pmid=12618437
# Hill2013 pmid=24297913
# Miyazaki2016 pmid=27688023
# Touhara2014 pmid=24828502
# Suzuki2016 pmid=26494689
# Golan2004 pmid=14573597
# Meng2003 pmid=14517548
# Ito2011 pmid=21354427
# Hurtado-Gerrero2009 pmid=19097997
# Yaoi2007 pmid=17498741
# Thompson2015 pmid=25772148
# Barends2007 pmid=17420245
# Fujimoto2013 pmid=23486481
# Wu2015 pmid=26575439
# Pluvinage2017 pmid=28781080
# Dennis2006 pmid=16565725
# Abbott2009 pmid=19181667
# Hehemann_1_2012 pmid=23150581
# Ficko-Blean2008 pmid=18443291
# Zhu2009 pmid=20081828
# Sogabe2011 pmid=21543843
# Nam2015 pmid=26041776
# Nagae2007 pmid=17459873
# Kitamura2008 pmid=18981178
# Higgins2009 pmid=19608744
# van_Straaten2007 pmid=17502382
# van_Asselt2000 pmid=10684641
# Ndeh2017 pmid=28329766
# Jin2016 Jin Y, Petricevic M, John A, Raich L, Jenkins H, Portela De Souza L, Cuskin F, Gilbert HJ, Rovira C, Goddard-Borger ED, Williams SJ, and Davies GJ. ''A β-Mannanase with a Lysozyme-like Fold and a Novel Molecular Catalytic Mechanism.'' ACS Cent Sci. 2016 Nov [http://dx.doi.org/10.1021/acscentsci.6b00232 DOI:10.1021/acscentsci.6b00232]
# Ohnuma2014 pmid=24582745
# Thompson2012 pmid=22219371
# Xie2016 pmid=27777307
# Williams2014 pmid=24339341
# Hehemann_2_2012 pmid=22393053
# Huang2012 pmid=22992047
# Noach2016 pmid=27038508
# Alonso-Gil2016 pmid=28026180
# Huang2014 Huang CH, Zhu Z, Cheng YS, Chan HC, Ko TP, Chen CC, Wang I, Ho MR, Hsu ST, Zeng YF, Huang YN, Liu JR, Guo RT. ''Structure and Catalytic Mechanism of a Glycoside Hydrolase Family-127 β-L-Arabinofuranosidase (HypBA1).'' J Bioprocess Biotech. 2014 4:171 [http://dx.doi.org/10.4172/2155-9821.1000171 DOI:10.4172/2155-9821.1000171]
# Tsuda2015 pmid=26632508
# Barbirz2008 pmid=18547389

</biblio>

[[Category:Definitions and explanations]]

Syn/anti lateral protonation

2018-01-06T11:48:43Z

Wim Nerinckx: cosmetic

{{CuratorApproved}}
* [[Author]]: ^^^Wim Nerinckx^^^
* [[Responsible Curator]]: ^^^Spencer Williams^^^

----

== Overview ==

This page provides a table that summarizes the spatial positioning of the catalytic [[general acid]] residue in the active sites of [[glycoside hydrolase]]s, relative to the substrate. The table below updates those found in the seminal paper on this concept by Heightman and Vasella <cite>HeightmanVasella1999</cite>, and a following paper by Nerinckx ''et al.'' <cite>Nerinckx2005</cite>.

== Background ==

The ''"not from above, but from the side"'' concept of semi-lateral glycosidic oxygen [[General_acid/base|protonation]] by [[glycoside hydrolase]]s was introduced by Heightman and Vasella <cite>HeightmanVasella1999</cite>. It was originally only described for [[Anomeric centre (alpha and beta)|beta]]-equatorial [[glycoside hydrolase]]s, but appears to be equally applicable to enzymes acting on an [[Anomeric centre (alpha and beta)|alpha]]-axial glycosidic bond <cite>Nerinckx2005</cite>. When dividing [[Sub-site nomenclature|subsite -1]] into half-spaces by a plane defined by the glycosidic oxygen and C1' and H1' of the –1 glycoside, many ligand-complexed structures reveal that the [[General_acid/base|proton donor]] is positioned either in the ''syn'' half-space (near the ring-oxygen of the –1 glycoside), or in the ''anti'' half-space (on the opposite side of the ring-oxygen). Members of the same GH [[Families|family]] appear to share a common ''syn'' or ''anti'' [[General_acid/base|protonator]] arrangement and further, this specificity appears to be preserved within [[Clans|Clans]] of [[Families|families]]. This page's compilation of [[Sub-site nomenclature|subsite -1]] occupied complexes shows that about 70% of all GH [[Families|families]] are ''anti'' [[General_acid/base|protonators]].

Closer inspection of crystal structures of [[Sub-site nomenclature|–1/+1 subsite]]-spanning substrates, or substrate-analogue ligands, in complex with enzymes reveals a further intriguing corollary <cite>Nerinckx2005 Wu2012</cite>. In substrate-bound complexes with ''anti'' [[General_acid/base|protonating]] GH enzymes, the scissile [[Anomeric centre (alpha and beta)|anomeric bond]] (often studied using the thio-analogue) shows a dihedral angle φ (O5'-C1'-[O,S]x-Cx) that is in the lowest-energy synclinal (gauche) conformation. The rationale for this is that a minus synclinal dihedral angle φ for an equatorial glycosidic bond, or plus synclinal for an axial glycosidic bond <cite>Perez1978</cite>, allows for hyperconjugative overlap of the C1'-O5' antibonding orbital with an antiperiplanar-oriented lone pair orbital lobe of the glycosidic oxygen, thereby creating partial double bond character and stabilization of the glycosidic bond by 4–5 kcal/mol; this ground-state stabilizing phenomenon is known as the ‘exo-anomeric effect’ <cite>Cramer1997 Johnson2009 Alonso2016</cite>. ''Anti'' [[General_acid/base|protonation]] occurs on the glycosidic oxygen’s antiperiplanar lone pair, thereby removing the stabilizing exo-anomeric effect. This suggests that ''anti'' [[General_acid/base|protonation]] is an enzymic approach for lowering the activation barrier leading to the [[Transition state|transition state]] (Figure 1 centre).

''Syn'' [[General_acid/base|protonating]] [[glycoside hydrolase]]s apparently make use of a different approach <cite>Nerinckx2005 Wu2012</cite>. In many [[Sub-site nomenclature|–1/+1 subsite]]-spanning ligand complexes, the dihedral angle φ of the scissile anomeric bond has been rotated away from its lowest-energy synclinal position: clockwise to minus-anticlinal or antiperiplanar for beta-equatorial; counterclockwise to plus-anticlinal or antiperiplanar for alpha-axial [[Anomeric centre (alpha and beta)|anomeric bonds]]. This removes the hyperconjugative overlap and thus also the stabilizing exo-anomeric effect. And because of this rotation, a lone pair of the glycosidic oxygen is directed into the ''syn'' half-space, allowing it to be protonated by the ''syn''-positioned [[General_acid/base|proton donor]] (Figure 1 right).

[[File:Syn_anti.jpg|800px|thumb|center|Figure 1. Newman projections, with the glycosidic oxygen as proximal atom and the anomeric carbon as distal atom, showing ''anti'' (centre) versus ''syn'' (right) semi-lateral [[General_acid/base|protonation]] in beta-equatorial (top) and alpha-axial (bottom) [[glycoside hydrolase]]s. The indicated φ is the dihedral angle for O5'-C1'-O4-C4.]]

== Table of ''syn/anti'' protonation examples ==

This table contains only one example per GH [[Families|family]] of a ligand-complexed protein structure where the ''syn'' or ''anti'' positioning of the [[General_acid/base|proton donor]] can be clearly observed; other examples may be available on a [[Families|family-by-family]] basis. The reader is thus advised to consult the [http://www.cazy.org/fam/acc_GH.html#table CAZy database] for a current, comprehensive list of CAZyme structures. Where available, the selected examples are Michaelis-type complexes with the ligand spanning the [[Sub-site nomenclature|-1/+1 subsites]], since these have an intact glycosidic or thioglycosidic bond, or are ''N''-analogs of the substrate (''e.g.'' acarbose). In some examples, the [[General_acid/base|proton donor]] has been mutated (''e.g.'', to the corresponding amide or to an alanine), and in those cases one may wish to look at a superposition of the given PDB example with the structure of the native enzyme. If a Michaelis-type complex is not yet available, the second and third example choices, respectively, are trapped glycosyl-enzyme [[intermediate]]s and product complexes where [[Sub-site nomenclature|subsite -1]] is occupied.

''Please also be aware that this is a large table with many data. Please contact the page Author or Responsible Curator with corrections.''

=== Table ===
This table can be re-sorted by clicking on the icons in the header (''javascript must be turned on in your browser''). To reset the page to be sorted by GH family, click the ''View'' tab at the very top of the page.

{| {{Prettytable}} class="sortable"
|- valign="top"
! '''Family'''
! '''Clan'''
! '''Structure fold '''
! '''Anomeric specificity'''
! '''Mechanism'''
! '''''Syn/anti'' protonator'''
! '''Example PDB ID'''
! '''Enzyme'''
! '''Organism'''
! '''Ligand'''
! '''General acid'''
! '''Nucleophile or General base'''
! '''Reference'''
|-
| [[GH1]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2cer 2cer]
| β-glycosidase S
| ''Sulfolobus solfataricus'' P2
| phenethyl glucoimidazole
| '''Glu206'''
| Glu387
| <cite>Gloster2006</cite>
|-
| [[GH2]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vzu 2vzu]
| exo-β-glucosaminidase
| ''Amicolatopsis orientalis''
| PNP-β-{{Smallcaps|d}}-glucosamine
| '''Glu469'''
| Glu541
| <cite>van_Bueren2009</cite>
|-
| [[GH3]]
| none
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1iex 1iex]
| exo-1,3-1,4-glucanase
| ''Hordeum vulgare''
| thiocellobiose
| '''Glu491'''
| Asp285
| <cite>Hrmova2001</cite>
|-
| [[GH5]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1h2j 1h2j]
| endo-β-1,4-glucanase
| ''Bacillus agaradhaerens''
| 2',4'-DNP-2-F-cellobioside
| '''Glu129'''
| Glu228
| <cite>Varrot2003</cite>
|-
| [[GH6]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1qjw 1qjw]
| cellobiohydrolase 2
| ''Hypocrea jecorina''
| (Glc)2-S-(Glc)2
| '''Asp221'''
| debated
| <cite>Zhou1999</cite>
|-
| [[GH7]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1ovw 1ovw]
| endo-1,4-glucanase
| ''Fusarium oxysporum''
| thio-(Glc)5
| '''Glu202'''
| Glu197
| <cite>Sulzenbacher1999</cite>
|-
| [[GH8]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1kwf 1kwf]
| endo-1,4-glucanase
| ''Clostridium thermocellum''
| cellopentaose
| '''Glu95'''
| Asp278
| <cite>Guerin2002</cite>
|-
| [[GH9]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1rq5 1rq5]
| cellobiohydrolase
| ''Clostridium thermocellum''
| cellotetraose
| '''Glu795'''
| Asp383
| <cite>Schubot2004</cite>
|-
| [[GH10]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2d24 2d24]
| β-1,4-xylanase
| ''Streptomyces olivaceoviridis'' E-86
| xylopentaose
| '''Glu128'''
| Glu236
| <cite>Suzuki2009</cite>
|-
| [[GH11]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}4hk8 4hk8]
| endo-β-1,4-xylanase
| ''Hypocrea jecorina''
| xylohexaose
| '''Glu177'''
| Glu86
| <cite>Wan2014</cite>
|-
| [[GH12]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1w2u 1w2u]
| endoglucanase
| ''Humicola grisea''
| thiocellotetraose
| '''Glu205'''
| Glu120
| <cite>Sandgren2004</cite>
|-
| [[GH13]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1cxk 1cxk]
| β-cyclodextrin glucanotransferase
| ''Bacillus circulans''
| maltononaose
| '''Glu257'''
| Asp229
| <cite>Uitdehaag1999</cite>
|-
| [[GH14]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1itc 1itc]
| β-amylase
| ''Bacillus cereus''
| maltopentaose
| '''Glu172'''
| Glu367
| <cite>Miyake2003</cite>
|-
| [[GH15]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1dog 1dog]
| glucoamylase
| ''Aspergillus awamori''
| 1-deoxynojirimycin
| '''Glu179'''
| Glu400
| <cite>Harris1993</cite>
|-
| [[GH16]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1urx 1urx]
| β-agarase A
| ''Zobellia galactanivorans''
| oligoagarose
| '''Glu152'''
| Glu147
| <cite>Allouch2004</cite>
|-
| [[GH17]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH1''
|
|
|
|
|
|
|-
| [[GH18]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1ffr 1ffr]
| chitinase A
| ''Serratia marcescens''
| (NAG)6
| '''Glu315'''
| internal
| <cite>Papanikolau2001</cite>
|-
| [[GH19]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}3wh1 3wh1]
| chitinase
| ''Bryum coronatum''
| (GlcNAc)4
| '''Glu61'''
| Glu70
| <cite>Ohnuma2014</cite>
|-
| [[GH20]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1c7s 1c7s]
| chitobiase
| ''Serratia marcescens''
| chitobiose
| '''Glu540'''
| internal
| <cite>Prag2000</cite>
|-
| [[GH22]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1h6m 1h6m]
| lysozyme C
| ''Gallus gallus''
| Chit-2-F-chitosyl
| '''Glu35'''
| Asp52
| <cite>Vocadlo2001</cite>
|-
| [[GH23]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1lsp 1lsp]
| lysozyme G
| ''Cygnus atratus''
| Bulgecin A
| '''Glu73'''
| internal
| <cite>Karlsen1996</cite>
|-
| [[GH24]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}148l 148l]
| lysozyme E
| Bacteriophage T4
| chitobiosyl
| '''Glu11'''
| Glu26
| <cite>Baldwin1993</cite>
|-
| [[GH26]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vx6 2vx6]
| exo-β-mannanase
| ''Cellvibrio japonicus'' Ueda107
| Gal1Man4
| '''Glu221'''
| Glu338
| <cite>Cartmell2008</cite>
|-
| [[GH27]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}} / beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3lrm 3lrm]
| α-galactosidase
| ''Saccharomyces cerevisiae''
| raffinose
| '''Asp209'''
| Asp141
| <cite>Fernandez-Leiro2010</cite>
|-
| [[GH28]]
| N
| β-helix
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}2uvf 2uvf]
| exo-polygalacturonosidase
| ''Yersinia enterocolitica'' ATCC9610D
| digalacturonic acid
| '''Asp402'''
| Asp381 Asp403
| <cite>Abbott2007</cite>
|-
| [[GH29]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| '''''syn'''''
| [{{PDBlink}}3uet 3uet]
| α-1,3/4-fucosidase
| ''Bifidobacterium longum'' subsp. infantis
| lacto-''N''-fucopentaose II
| '''Glu217'''
| Asp172
| <cite>Sakurama2012</cite>
|-
| [[GH30]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2y24 2y24]
| glucurono-xylanase
| ''Dickea chrysanthemi'' D1
| glucuronoxylan tetrasaccharide
| '''Glu163'''
| Glu253
| <cite>Urbanikova2011</cite>
|-
| [[GH31]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2qmj 2qmj]
| maltase-glucoamylase
| ''Homo sapiens''
| acarbose
| '''Asp542'''
| Asp443
| <cite>Sim2008</cite>
|-
| [[GH32]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2add 2add]
| fructan β-(2,1)-fructosidase
| ''Cichorium intybus''
| sucrose
| '''Glu201'''
| Asp22
| <cite>Verhaest2007</cite>
|-
| [[GH33]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1s0i 1s0i]
| transsialidase
| ''Trypanosoma cruzi''
| sialyllactose
| '''Asp59'''
| Tyr342
| <cite>Amaya2004</cite>
|-
| [[GH34]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4gzw 4gzw]
| N2 neuraminidase
| ''Influenza'' A Tanzania/205/2010 H3N2
| α-{{Smallcaps|d}}-Neup5Ac-(2,3)-β-{{Smallcaps|d}}-Galp-(1,4)-β-{{Smallcaps|d}}-GlcpNAc
| '''Asp151'''
| Tyr406
| <cite>Zhu2012</cite>
|-
| [[GH35]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3ogv 3ogv]
| β-galactosidase
| ''Hypocrea jecorina''
| 2-phenylethyl 1-thio-β-{{Smallcaps|d}}-galactopyranoside
| '''Glu200'''
| Glu298
| <cite>Maksimainen2011</cite>
|-
| [[GH36]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4fns 4fns]
| β-galactosidase
| ''Geobacillus stearothermophilus''
| 1-deoxy galactonojirimycin
| '''Asp584'''
| Asp478
| <cite>Merceron2012</cite>
|-
| [[GH37]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2jf4 2jf4]
| trehalase
| ''Escherechia coli''
| validoxylamine
| '''Asp312'''
| Glu496
| <cite>Gibson2007</cite>
|-
| [[GH38]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3czn 3czn]
| Golgi α-mannosidase II
| ''Drosophila melanogaster''
| GlcNAcMan(5)GlcNAc(2)
| '''Asp341'''
| Asp204
| <cite>Shah2008</cite>
|-
| [[GH39]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2bfg 2bfg]
| β-xylosidase
| ''Geobacillus stearothermophilus''
| 2,5-dinitrophenyl-β-{{Smallcaps|d}}-xyloside
| '''Glu160'''
| Glu278
| <cite>Czjzek2005</cite>
|-
| [[GH42]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ucf 4ucf]
| β-galactosidase
| ''Bifidobacterium bifidum''
| {{Smallcaps|d}}-galactose
| '''Glu161'''
| Glu320
| <cite>Godoy2016</cite>
|-
| [[GH43]]
| F
| 5-fold β-propeller
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3akh 3akh]
| exo-1,5-α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces avermitilis''
| α-1,5-arabinofuranotriose
| '''Glu196'''
| Asp220
| <cite>Fujimoto2010</cite>
|-
| [[GH44]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2eqd 2eqd]
| endoglucanase
| ''Clostridium thermocellum''
| cellooctaose
| '''Glu186'''
| Glu359
| <cite>Kitago2007</cite>
|-
| [[GH45]]
| none
| 6-stranded β-barrel
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4eng 4eng]
| endo-1,4-glucanase
| ''Humicola insolens''
| cellohexaose
| '''Asp121'''
| Asp10
| <cite>Davies1996</cite>
|-
| [[GH46]]
| I
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4olt 4olt]
| chitosanase
| ''Microbacterium sp.'' OU01
| hexa-glucosamine
| '''Glu25'''
| Asp43
| <cite>Lyu2014</cite>
|-
| [[GH47]]
| none
| (α/α)7
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}1x9d 1x9d]
| α-mannosidase I
| ''Homo sapiens''
| Me-2-S-(α-Man)-2-thio-α-Man
| '''Asp463'''
| Glu599
| <cite>Karaveg2005</cite>, <cite>Nerinckx2008</cite>
|-
| [[GH48]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH8''
|
|
|
|
|
|
|-
| [[GH49]]
| N
| β-helix
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH28''
|
|
|
|
|
|
|-
| [[GH50]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4bq5 4bq5]
| exo-β-agarase
| ''Saccharophagus degradans''
| neoagarotetraose
| '''Glu535'''
| Glu695
| <cite>Pluvinage2013</cite>
|-
| [[GH51]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1qw9 1qw9]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Geobacillus stearothermophilus''
| PNP-{{Smallcaps|l}}-arabinofuranoside
| '''Glu175'''
| Glu294
| <cite>Hoevel2003</cite>
|-
| [[GH52]]
| O
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4c1p 4c1p]
| β-xylosidase
| ''Geobacillus thermoglucosidasius''
| xylobiose
| '''Asp517'''
| Glu537
| <cite>Espina2014</cite>
|-
| [[GH53]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2ccr 2ccr]
| β-1,4-galactanase
| ''Bacillus licheniformis''
| galactotriose
| '''Glu165'''
| Glu263
| <cite>Le_Nours2009</cite>
|-
| [[GH54]]
| none
| β-sandwich
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1wd4 1wd4]
| α-{{Smallcaps|l}}-arabinofuranosidase B
| ''Aspergillus kawachii''
| {{Smallcaps|l}}-arabinofuranose
| '''Asp297'''
| Glu221
| <cite>Miyanaga2004</cite>
|-
| [[GH55]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4tz5 4tz5]
| exo-β-1,3-glucanase
| ''Streptomyces sp.'' SirexAA-E
| laminarihexaose
| '''Glu502'''
| unknown
| <cite>Bianchetti2015</cite>
|-
| [[GH56]]
| none
| (β/α)7
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1fcv 1fcv]
| hyaluronidase
| ''Apis mellifera''
| (hyaluron.)4
| '''Glu113'''
| internal
| <cite>Markovic-Housley2000</cite>
|-
| [[GH57]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1k1y 1k1y]
| glucanotransferase
| ''Thermococcus litoralis''
| acarbose
| '''Asp214'''
| Glu123
| <cite>Imamura2003</cite>
|-
| [[GH59]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ccc 4ccc]
| β-galactocerebrosidase
| ''Mus musculus''
| PNP-β-{{Smallcaps|d}}-galactoside
| '''Glu182'''
| Glu258
| <cite>Hill2013</cite>
|-
| [[GH62]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| unknown
| ''predicted anti by clan''
| ''see at GH43''
|
|
|
|
|
|
|-
| [[GH63]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5ca3 5ca3]
| α-glucosidase
| ''Escherechia coli''
| glucose and lactose
| '''Asp501'''
| Glu727
| <cite>Miyazaki2016</cite>
|-
| [[GH65]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| '''''anti'''''
| [{{PDBlink}}4ktr 4ktr]
| 2-O-α-glucosylglycerol phosphorylase
| ''Bacillus selenitireducens''
| isofagomine
| '''Glu475'''
| phosphate
| <cite>Touhara2014</cite>
|-
| [[GH66]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5axh 5axh]
| dextranase
| ''Thermoanaerobacter pseudethanolicus''
| isomaltohexaose
| '''Glu374'''
| Asp312
| <cite>Suzuki2016</cite>
|-
| [[GH67]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}1l8n 1l8n]
| α-glucuronidase
| ''Geobacillus stearothermophilus''
| 4-O-methyl-{{Smallcaps|d}}-glucuronic acid and xylotriose
| '''Glu286'''
| Asp364 Glu392
| <cite>Golan2004</cite>
|-
| [[GH68]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}1pt2 1pt2]
| levansucrase
| ''Bacillus subtilis''
| sucrose
| '''Glu342'''
| Asp86
| <cite>Meng2003</cite>
|-
| [[GH70]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3aic 3aic]
| glucansucrase
| ''Streptococcus mutans''
| α-acarbose
| '''Glu515'''
| Asp477
| <cite>Ito2011</cite>
|-
| [[GH72]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w62 2w62]
| β-1,3-glucanotransferase
| ''Saccharomyces cerevisiae'' S288C
| laminaripentaose
| '''Glu176'''
| Glu275
| <cite>Hurtado-Gerrero2009</cite>
|-
| [[GH74]]
| none
| 7-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}2ebs 2ebs]
| cellobiohydrolase (OXG-RCBH)
| ''Geotrichum sp.'' m128
| xyloglucan heptasaccharide
| '''Asp465'''
| Asp35
| <cite>Yaoi2007</cite>
|-
| [[GH76]]
| none
| (α/α)6
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5agd 5agd]
| endo-α-1,6-mannanase
| ''Bacillus circulans''
| α-1,6-mannopentaose
| '''Asp125'''
| Asp124
| <cite>Thompson2015</cite>
|-
| [[GH77]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2oww 2oww]
| 4-α-glucanotransferase
| ''Thermus thermofilus''
| acarbose + 4-deoxy-α-{{Smallcaps|d}}-glucose
| '''Glu340'''
| Asp293
| <cite>Barends2007</cite>
|-
| [[GH78]]
| H
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}3w5n 3w5n]
| α-{{Smallcaps|l}}-rhamnosidase
| ''Streptomyces avermitilis''
| {{Smallcaps|l}}-rhamnose
| '''Glu636'''
| Glu895
| <cite>Fujimoto2013</cite>
|-
| [[GH79]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5e9c 5e9c]
| heparanase
| ''Homo sapiens''
| heparin tetrasaccharide
| '''Glu225'''
| Glu343
| <cite>Wu2015</cite>
|-
| [[GH80]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH24''
|
|
|
|
|
|
|-
| [[GH81]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5t4g 5t4g]
| endo-β-1,3-glucanase
| ''Bacillus halodurans'' C-125
| laminarin
| '''Asp466'''
| Glu542
| <cite>Pluvinage2017</cite>
|-
| [[GH83]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH33''
|
|
|
|
|
|
|-
| [[GH84]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2chn 2chn]
| β-''N''-acetyl-glucosaminidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| NAG-thiazoline
| '''Glu242'''
| internal
| <cite>Dennis2006</cite>
|-
| [[GH85]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2w92 2w92]
| endo-β-''N''-acetyl-glucosaminidase D
| ''Streptococcus pneumoniae'' TIGR4
| NAG-thiazoline
| '''Glu337'''
| internal
| <cite>Abbott2009</cite>
|-
| [[GH86]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4aw7 4aw7]
| β-porphyranase
| ''Bacteroides plebeius''
| porphyran fragment
| '''Glu152'''
| Glu279
| <cite>Hehemann_1_2012</cite>
|-
| [[GH89]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}2vcb 2vcb]
| α-''N''-acetyl-glucosaminidase
| ''Clostridium perfringens''
| PUGNAc
| '''Glu483'''
| Glu601
| <cite>Ficko-Blean2008</cite>
|-
| [[GH92]]
| none
| (α/α)6 and β-sandw.
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ww1 2ww1]
| α-1,2-mannosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| thiomannobioside
| '''Glu533'''
| Asp644 Asp642
| <cite>Zhu2009</cite>
|-
| [[GH93]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3a72 3a72]
| exo-arabinanase
| ''Penicillium chrysogenum''
| arabinobiose
| '''Glu246'''
| Glu174
| <cite>Sogabe2011</cite>
|-
| [[GH94]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}4zli 4zli]
| cellobionic acid phosphorylase
| ''Saccharophagus degradans''
| 3-O-β-{{Smallcaps|d}}-glucopyranosyl-α-{{Smallcaps|d}}-glucopyranuronic acid
| '''Asp472'''
| phosphate
| <cite>Nam2015</cite>
|-
| [[GH95]]
| none
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2ead 2ead]
| α-1,2-{{Smallcaps|l}}-fucosidase
| ''Bifidobacterium bifidum''
| Fuc-α-1,2-Gal
| '''Glu566'''
| Asn423 Asp766
| <cite>Nagae2007</cite>
|-
| [[GH97]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining + inverting
| '''''anti'''''
| [{{PDBlink}}2zq0 2zq0]
| α-glucosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| acarbose
| '''Glu532'''
| Glu508
| <cite>Kitamura2008</cite>
|-
| [[GH98]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2wmg 2wmg]
| endo-β-1,4-galactosidase
| ''Streptococcus pneumoniae''
| A-LewisY pentasaccharide
| '''Glu158'''
| Asp251 Glu301
| <cite>Higgins2009</cite>
|-
| [[GH99]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4ad4 4ad4]
| endo-α-mannosidase
| ''Bacteroides xylanisolvens''
| glucose-1,3-isofagomine and α-1,2- mannobiose
| '''Glu336'''
| debated
| <cite>Thompson2012</cite>
|-
| [[GH100]]
| none
| (α/α)6 core
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5gop 5gop]
| invertase
| ''Anabaena (Nostoc) sp.'' pcc7120
| sucrose
| '''Asp188'''
| Glu414
| <cite>Xie2016</cite>
|-
| [[GH102]]
| none
| double-ψ β-barrel
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}2pi8 2pi8]
| lytic transglycosylase A
| ''Escherichia coli''
| chitohexaose
| '''Asp308'''
| none
| <cite>van_Straaten2007</cite>
|-
| [[GH103]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| '''''syn'''''
| [{{PDBlink}}1d0k 1d0k]
| lytic transglycosylase SLT35
| ''Escherichia coli''
| murodipeptides
| '''Glu162'''
| internal
| <cite>van_Asselt2000</cite>
|-
| [[GH106]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5mwk 5mwk]
| α-{{Smallcaps|l}}-rhamnosidase BT_0986
| ''Bacteroides thetaiotaomicron''
| pectin heptasaccharide
| '''Glu461'''
| Glu593 or Glu561
| <cite>Ndeh2017</cite>
|-
| [[GH113]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}4cd8 4cd8]
| β-mannanase
| ''Alicyclobacillus acidocaldarius''
| mannobioimidazole
| '''Glu151'''
| Glu231
| <cite>Williams2014</cite>
|-
| [[GH116]]
| O
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at GH52''
|
|
|
|
|
|
|-
| [[GH117]]
| none
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| '''''anti'''''
| [{{PDBlink}}4ak7 4ak7]
| α-1,3-3,6-anhydro-{{Smallcaps|l}}-galactosidase
| ''Bacteroides plebeius''
| neoagarobiose
| '''His302'''
| Asp90
| <cite>Hehemann_2_2012</cite>
|-
| [[GH120]]
| none
| parallel β-helix and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3vsv 3vsv]
| β-xylosidase XylC
| ''Thermoanaerobacterium saccharolyticum'' JW/SL-YS485
| {{Smallcaps|d}}-xylose
| '''Glu405'''
| Asp382
| <cite>Huang2012</cite>
|-
| [[GH123]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| '''''anti'''''
| [{{PDBlink}}5fr0 5fr0]
| exo-β-N-acetyl-galactosaminidase
| ''Clostridium perfringens''
| ''N''-difluoroacetyl-{{Smallcaps|d}}-galactosamine
| '''Glu345'''
| internal
| <cite>Noach2016</cite>
|-
| [[GH125]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5m7y 5m7y]
| exo-α-1,6-mannosidase
| ''Clostridium perfringens''
| 1,6-α-mannotriose
| '''Asp220'''
| Glu393
| <cite>Alonso-Gil2016</cite>
|-
| [[GH127]]
| none
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| '''''anti'''''
| [{{PDBlink}}3wrg 3wrg]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bifidobacterium longum''
| {{Smallcaps|l}}-arabinose
| '''Glu322'''
| Cys417
| <cite>Huang2014</cite>
|-
| [[GH128]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH1''
|
|
|
|
|
|
|-
| [[GH130]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}5b0s 5b0s]
| β-1,2-mannobiose phosphorylase
| ''Listeria innocua''
| β-1,2-mannotriose
| '''Asp141''' relay
| phosphate
| <cite>Tsuda2015</cite>
|-
| [[GH134]]
| none
| β + α
| beta-{{Smallcaps|d}}
| inverting
| '''''syn'''''
| [{{PDBlink}}5jug 5jug]
| β-mannanase
| ''Streptomyces sp.''
| mannopentaose
| '''Glu45'''
| Asp57
| <cite>Jin2016</cite>
|-
| [[GH137]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|l}}
| unknown
| '''''anti'''''
| [{{PDBlink}}5mui 5mui]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0996
| ''Bacteroides thetaiotaomicron''
| pectin oligosaccharide
| '''Glu240'''
| Glu159
| <cite>Ndeh2017</cite>
|-
| [[N. C.]]
| N. C.
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| '''''anti'''''
| [{{PDBlink}}2vjj 2vjj]
| endo-α-N-acetylglucosaminidase
| Bacteriophage HK620
| O18A1 O-antigen hexasaccharide
| '''Asp339'''
| Glu372
| <cite>Barbirz2008</cite>
|}

== References ==

<biblio>
# HeightmanVasella1999 Heightman TD and Vasella AT. ''Recent Insights into Inhibition, Structure, and Mechanism of Configuration-Retaining Glycosidases.'' Angew Chem Int Ed. 1999 38(6):750-770. [http://www3.interscience.wiley.com/journal/55000581/abstract Article online].
# Nerinckx2005 pmid=15642336
# Wu2012 pmid=23137336
# Perez1978 Pérez S and Marchessault RH. ''The exo-anomeric effect: experimental evidence from crystal structures.'' Carbohydr res. 1978 65:114-120. [http://dx.doi.org/10.1016/S0008-6215(00)84218-4 DOI:10.1016/S0008-6215(00)84218-4]
# Cramer1997 Cramer CJ, Truhlar DG, and French AD. ''Exo-anomeric effects on energies and geometries of different conformations of glucose and related systems in the gas phase and aqueous solution.'' Carbohydr res. 1997 298:1-14. [http://dx.doi.org/10.1016/S0008-6215(96)00297-2 DOI:10.1016/S0008-6215(96)00297-2]
# Johnson2009 pmid=19733839
# Alonso2016 pmid=26889578
# Gloster2006 pmid=17002288
# van_Bueren2009 pmid=18976664
# Hrmova2001 pmid=11709165
# Varrot2003 pmid=12595701
# Zhou1999 pmid=10508787
# Sulzenbacher1999 pmid=10200171
# Urbanikova2011 pmid=21501386
# Guerin2002 pmid=11884144
# Schubot2004 pmid=14756552
# Suzuki2009 pmid=19279191
# Wan2014 pmid=24419374
# Sandgren2004 pmid=15364577
# Uitdehaag1999 pmid=10331869
# Miyake2003 pmid=12741813
# Harris1993 pmid=8431441
# Allouch2004 pmid=15062085
# Papanikolau2001 pmid=11560481
# Prag2000 pmid=10884356
# Vocadlo2001 pmid=11518970
# Karlsen1996 pmid=15299731
# Baldwin1993 pmid=8259514
# Cartmell2008 pmid=18799462
# Fernandez-Leiro2010 pmid=20592022
# Abbott2007 pmid=17397864
# Sakurama2012 pmid=22451675
# Sim2008 pmid=18036614
# Verhaest2007 pmid=17335500
# Amaya2004 pmid=15130470
# Zhu2012 pmid=23015718
# Maksimainen2011 pmid=21130883
# Merceron2012 pmid=23012371
# Gibson2007 pmid=17455176
# Shah2008 pmid=18599462
# Czjzek2005 pmid=16212978
# Godoy2016 pmid=27685756
# Fujimoto2010 pmid=20739278
# Kitago2007 pmid=17905739
# Davies1996 pmid=15299721
# Lyu2014 pmid=24766439
# Karaveg2005 pmid=15713668
# Nerinckx2008 pmid=18619586
# Pluvinage2013 pmid=23921382
# Hoevel2003 pmid=14517232
# Espina2014 pmid=24816105
# Le_Nours2009 pmid=19089956
# Miyanaga2004 pmid=15292273
# Bianchetti2015 pmid=25752603
# Markovic-Housley2000 pmid=11080624
# Imamura2003 pmid=12618437
# Hill2013 pmid=24297913
# Miyazaki2016 pmid=27688023
# Touhara2014 pmid=24828502
# Suzuki2016 pmid=26494689
# Golan2004 pmid=14573597
# Meng2003 pmid=14517548
# Ito2011 pmid=21354427
# Hurtado-Gerrero2009 pmid=19097997
# Yaoi2007 pmid=17498741
# Thompson2015 pmid=25772148
# Barends2007 pmid=17420245
# Fujimoto2013 pmid=23486481
# Wu2015 pmid=26575439
# Pluvinage2017 pmid=28781080
# Dennis2006 pmid=16565725
# Abbott2009 pmid=19181667
# Hehemann_1_2012 pmid=23150581
# Ficko-Blean2008 pmid=18443291
# Zhu2009 pmid=20081828
# Sogabe2011 pmid=21543843
# Nam2015 pmid=26041776
# Nagae2007 pmid=17459873
# Kitamura2008 pmid=18981178
# Higgins2009 pmid=19608744
# van_Straaten2007 pmid=17502382
# van_Asselt2000 pmid=10684641
# Ndeh2017 pmid=28329766
# Jin2016 Jin Y, Petricevic M, John A, Raich L, Jenkins H, Portela De Souza L, Cuskin F, Gilbert HJ, Rovira C, Goddard-Borger ED, Williams SJ, and Davies GJ. ''A β-Mannanase with a Lysozyme-like Fold and a Novel Molecular Catalytic Mechanism.'' ACS Cent Sci. 2016 Nov [http://dx.doi.org/10.1021/acscentsci.6b00232 DOI:10.1021/acscentsci.6b00232]
# Ohnuma2014 pmid=24582745
# Thompson2012 pmid=22219371
# Xie2016 pmid=27777307
# Williams2014 pmid=24339341
# Hehemann_2_2012 pmid=22393053
# Huang2012 pmid=22992047
# Noach2016 pmid=27038508
# Alonso-Gil2016 pmid=28026180
# Huang2014 Huang CH, Zhu Z, Cheng YS, Chan HC, Ko TP, Chen CC, Wang I, Ho MR, Hsu ST, Zeng YF, Huang YN, Liu JR, Guo RT. ''Structure and Catalytic Mechanism of a Glycoside Hydrolase Family-127 β-L-Arabinofuranosidase (HypBA1).'' J Bioprocess Biotech. 2014 4:171 [http://dx.doi.org/10.4172/2155-9821.1000171 DOI:10.4172/2155-9821.1000171]
# Tsuda2015 pmid=26632508
# Barbirz2008 pmid=18547389

</biblio>

[[Category:Definitions and explanations]]

Syn/anti lateral protonation

2017-12-24T22:26:49Z

Wim Nerinckx:

{{CuratorApproved}}
* [[Author]]: ^^^Wim Nerinckx^^^
* [[Responsible Curator]]: ^^^Spencer Williams^^^

----

== Overview ==

This page provides a table that summarizes the spatial positioning of the catalytic [[general acid]] residue in the active sites of [[glycoside hydrolase]]s, relative to the substrate. The table below updates those found in the seminal paper on this concept by Heightman and Vasella <cite>HeightmanVasella1999</cite>, and a following paper by Nerinckx ''et al.'' <cite>Nerinckx2005</cite>.

== Background ==

The ''"not from above, but from the side"'' concept of semi-lateral glycosidic oxygen [[General_acid/base|protonation]] by [[glycoside hydrolase]]s was introduced by Heightman and Vasella <cite>HeightmanVasella1999</cite>. It was originally only described for [[Anomeric centre (alpha and beta)|beta]]-equatorial [[glycoside hydrolase]]s, but appears to be equally applicable to enzymes acting on an [[Anomeric centre (alpha and beta)|alpha]]-axial glycosidic bond <cite>Nerinckx2005</cite>. When dividing [[Sub-site nomenclature|subsite -1]] into half-spaces by a plane defined by the glycosidic oxygen and C1' and H1' of the –1 glycoside, many ligand-complexed structures reveal that the [[General_acid/base|proton donor]] is positioned either in the ''syn'' half-space (near the ring-oxygen of the –1 glycoside), or in the ''anti'' half-space (on the opposite side of the ring-oxygen). Members of the same GH [[Families|family]] appear to share a common ''syn'' or ''anti'' [[General_acid/base|protonator]] arrangement and further, this specificity appears to be preserved within [[Clans|Clans]] of [[Families|families]]. This page's compilation of [[Sub-site nomenclature|subsite -1]] occupied complexes shows that about 70% of all GH [[Families|families]] are ''anti'' [[General_acid/base|protonators]].

Closer inspection of crystal structures of [[Sub-site nomenclature|–1/+1 subsite]]-spanning substrates, or substrate-analogue ligands, in complex with enzymes reveals a further intriguing corollary <cite>Nerinckx2005 Wu2012</cite>. In substrate-bound complexes with ''anti'' [[General_acid/base|protonating]] GH enzymes, the scissile [[Anomeric centre (alpha and beta)|anomeric bond]] (often studied using the thio-analogue) shows a dihedral angle φ (O5'-C1'-[O,S]x-Cx) that is in the lowest-energy synclinal (gauche) conformation. The rationale for this is that a minus synclinal dihedral angle φ for an equatorial glycosidic bond, or plus synclinal for an axial glycosidic bond <cite>Perez1978</cite>, allows for hyperconjugative overlap of the C1'-O5' antibonding orbital with an antiperiplanar-oriented lone pair orbital lobe of the glycosidic oxygen, thereby creating partial double bond character and stabilization of the glycosidic bond by 4–5 kcal/mol; this ground-state stabilizing phenomenon is known as the ‘exo-anomeric effect’ <cite>Cramer1997 Johnson2009 Alonso2016</cite>. ''Anti'' [[General_acid/base|protonation]] occurs on the glycosidic oxygen’s antiperiplanar lone pair, thereby removing the stabilizing exo-anomeric effect. This suggests that ''anti'' [[General_acid/base|protonation]] is an enzymic approach for lowering the activation barrier leading to the [[Transition state|transition state]] (Figure 1 centre).

''Syn'' [[General_acid/base|protonating]] [[glycoside hydrolase]]s apparently make use of a different approach <cite>Nerinckx2005 Wu2012</cite>. In many [[Sub-site nomenclature|–1/+1 subsite]]-spanning ligand complexes, the dihedral angle φ of the scissile anomeric bond has been rotated away from its lowest-energy synclinal position: clockwise to minus-anticlinal or antiperiplanar for beta-equatorial; counterclockwise to plus-anticlinal or antiperiplanar for alpha-axial [[Anomeric centre (alpha and beta)|anomeric bonds]]. This removes the hyperconjugative overlap and thus also the stabilizing exo-anomeric effect. And because of this rotation, a lone pair of the glycosidic oxygen is directed into the ''syn'' half-space, allowing it to be protonated by the ''syn''-positioned [[General_acid/base|proton donor]] (Figure 1 right).

[[File:Syn_anti.jpg|800px|thumb|center|Figure 1. Newman projections, with the glycosidic oxygen as proximal atom and the anomeric carbon as distal atom, showing ''anti'' (centre) versus ''syn'' (right) semi-lateral [[General_acid/base|protonation]] in beta-equatorial (top) and alpha-axial (bottom) [[glycoside hydrolase]]s. The indicated φ is the dihedral angle for O5'-C1'-O4-C4.]]

== Table of ''syn/anti'' protonation examples ==

This table contains only one example per GH [[Families|family]] of a ligand-complexed protein structure where the ''syn'' or ''anti'' positioning of the [[General_acid/base|proton donor]] can be clearly observed; other examples may be available on a [[Families|family-by-family]] basis. The reader is thus advised to consult the [http://www.cazy.org/fam/acc_GH.html#table CAZy database] for a current, comprehensive list of CAZyme structures. Where available, the selected examples are Michaelis-type complexes with the ligand spanning the [[Sub-site nomenclature|-1/+1 subsites]], since these have an intact glycosidic or thioglycosidic bond, or are ''N''-analogs of the substrate (''e.g.'' acarbose). In some examples, the [[General_acid/base|proton donor]] has been mutated (''e.g.'', to the corresponding amide or to an alanine), and in those cases one may wish to look at a superposition of the given PDB example with the structure of the native enzyme. If a Michaelis-type complex is not yet available, the second and third example choices, respectively, are trapped glycosyl-enzyme [[intermediate]]s and product complexes where [[Sub-site nomenclature|subsite -1]] is occupied.

''Please also be aware that this is a large table with many data. Please contact the page Author or Responsible Curator with corrections.''

=== Table ===
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{| {{Prettytable}} class="sortable"
|- valign="top"
! '''Family'''
! '''Clan'''
! '''Structure fold '''
! '''Anomeric specificity'''
! '''Mechanism'''
! '''''Syn/anti'' protonator'''
! '''Example PDB ID'''
! '''Enzyme'''
! '''Organism'''
! '''Ligand'''
! '''General acid'''
! '''Nucleophile or General base'''
! '''Reference'''
|-
| [[GH1]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2cer 2cer]
| β-glycosidase S
| ''Sulfolobus solfataricus'' P2
| phenethyl glucoimidazole
| Glu206
| Glu387
| <cite>Gloster2006</cite>
|-
| [[GH2]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| ''anti''
| [{{PDBlink}}2vzu 2vzu]
| exo-β-glucosaminidase
| ''Amicolatopsis orientalis''
| PNP-β-{{Smallcaps|d}}-glucosamine
| Glu469
| Glu541
| <cite>van_Bueren2009</cite>
|-
| [[GH3]]
| none
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| ''anti''
| [{{PDBlink}}1iex 1iex]
| exo-1,3-1,4-glucanase
| ''Hordeum vulgare''
| thiocellobiose
| Glu491
| Asp285
| <cite>Hrmova2001</cite>
|-
| [[GH5]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}1h2j 1h2j]
| endo-β-1,4-glucanase
| ''Bacillus agaradhaerens''
| 2',4'-DNP-2-F-cellobioside
| Glu129
| Glu228
| <cite>Varrot2003</cite>
|-
| [[GH6]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}1qjw 1qjw]
| cellobiohydrolase 2
| ''Hypocrea jecorina''
| (Glc)2-S-(Glc)2
| Asp221
| debated
| <cite>Zhou1999</cite>
|-
| [[GH7]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| ''syn''
| [{{PDBlink}}1ovw 1ovw]
| endo-1,4-glucanase
| ''Fusarium oxysporum''
| thio-(Glc)5
| Glu202
| Glu197
| <cite>Sulzenbacher1999</cite>
|-
| [[GH8]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}1kwf 1kwf]
| endo-1,4-glucanase
| ''Clostridium thermocellum''
| cellopentaose
| Glu95
| Asp278
| <cite>Guerin2002</cite>
|-
| [[GH9]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}1rq5 1rq5]
| cellobiohydrolase
| ''Clostridium thermocellum''
| cellotetraose
| Glu795
| Asp383
| <cite>Schubot2004</cite>
|-
| [[GH10]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2d24 2d24]
| β-1,4-xylanase
| ''Streptomyces olivaceoviridis'' E-86
| xylopentaose
| Glu128
| Glu236
| <cite>Suzuki2009</cite>
|-
| [[GH11]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| ''syn''
| [{{PDBlink}}4hk8 4hk8]
| endo-β-1,4-xylanase
| ''Hypocrea jecorina''
| xylohexaose
| Glu177
| Glu86
| <cite>Wan2014</cite>
|-
| [[GH12]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| ''syn''
| [{{PDBlink}}1w2u 1w2u]
| endoglucanase
| ''Humicola grisea''
| thiocellotetraose
| Glu205
| Glu120
| <cite>Sandgren2004</cite>
|-
| [[GH13]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}1cxk 1cxk]
| β-cyclodextrin glucanotransferase
| ''Bacillus circulans''
| maltononaose
| Glu257
| Asp229
| <cite>Uitdehaag1999</cite>
|-
| [[GH14]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}1itc 1itc]
| β-amylase
| ''Bacillus cereus''
| maltopentaose
| Glu172
| Glu367
| <cite>Miyake2003</cite>
|-
| [[GH15]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}1dog 1dog]
| glucoamylase
| ''Aspergillus awamori''
| 1-deoxynojirimycin
| Glu179
| Glu400
| <cite>Harris1993</cite>
|-
| [[GH16]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| ''syn''
| [{{PDBlink}}1urx 1urx]
| β-agarase A
| ''Zobellia galactanivorans''
| oligoagarose
| Glu152
| Glu147
| <cite>Allouch2004</cite>
|-
| [[GH17]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH1''
|
|
|
|
|
|
|-
| [[GH18]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}1ffr 1ffr]
| chitinase A
| ''Serratia marcescens''
| (NAG)6
| Glu315
| internal
| <cite>Papanikolau2001</cite>
|-
| [[GH19]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}3wh1 3wh1]
| chitinase
| ''Bryum coronatum''
| (GlcNAc)4
| Glu61
| Glu70
| <cite>Ohnuma2014</cite>
|-
| [[GH20]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}1c7s 1c7s]
| chitobiase
| ''Serratia marcescens''
| chitobiose
| Glu540
| internal
| <cite>Prag2000</cite>
|-
| [[GH22]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| ''syn''
| [{{PDBlink}}1h6m 1h6m]
| lysozyme C
| ''Gallus gallus''
| Chit-2-F-chitosyl
| Glu35
| Asp52
| <cite>Vocadlo2001</cite>
|-
| [[GH23]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}1lsp 1lsp]
| lysozyme G
| ''Cygnus atratus''
| Bulgecin A
| Glu73
| internal
| <cite>Karlsen1996</cite>
|-
| [[GH24]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}148l 148l]
| lysozyme E
| Bacteriophage T4
| chitobiosyl
| Glu11
| Glu26
| <cite>Baldwin1993</cite>
|-
| [[GH26]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2vx6 2vx6]
| exo-β-mannanase
| ''Cellvibrio japonicus'' Ueda107
| Gal1Man4
| Glu221
| Glu338
| <cite>Cartmell2008</cite>
|-
| [[GH27]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}} / beta-{{Smallcaps|l}}
| retaining
| ''anti''
| [{{PDBlink}}3lrm 3lrm]
| α-galactosidase
| ''Saccharomyces cerevisiae''
| raffinose
| Asp209
| Asp141
| <cite>Fernandez-Leiro2010</cite>
|-
| [[GH28]]
| N
| β-helix
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| ''anti''
| [{{PDBlink}}2uvf 2uvf]
| exo-polygalacturonosidase
| ''Yersinia enterocolitica'' ATCC9610D
| digalacturonic acid
| Asp402
| Asp381 Asp403
| <cite>Abbott2007</cite>
|-
| [[GH29]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| ''syn''
| [{{PDBlink}}3uet 3uet]
| α-1,3/4-fucosidase
| ''Bifidobacterium longum'' subsp. infantis
| lacto-''N''-fucopentaose II
| Glu217
| Asp172
| <cite>Sakurama2012</cite>
|-
| [[GH30]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2y24 2y24]
| glucurono-xylanase
| ''Dickea chrysanthemi'' D1
| glucuronoxylan tetrasaccharide
| Glu163
| Glu253
| <cite>Urbanikova2011</cite>
|-
| [[GH31]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2qmj 2qmj]
| maltase-glucoamylase
| ''Homo sapiens''
| acarbose
| Asp542
| Asp443
| <cite>Sim2008</cite>
|-
| [[GH32]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2add 2add]
| fructan β-(2,1)-fructosidase
| ''Cichorium intybus''
| sucrose
| Glu201
| Asp22
| <cite>Verhaest2007</cite>
|-
| [[GH33]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}1s0i 1s0i]
| transsialidase
| ''Trypanosoma cruzi''
| sialyllactose
| Asp59
| Tyr342
| <cite>Amaya2004</cite>
|-
| [[GH34]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}4gzw 4gzw]
| N2 neuraminidase
| ''Influenza'' A Tanzania/205/2010 H3N2
| α-{{Smallcaps|d}}-Neup5Ac-(2,3)-β-{{Smallcaps|d}}-Galp-(1,4)-β-{{Smallcaps|d}}-GlcpNAc
| Asp151
| Tyr406
| <cite>Zhu2012</cite>
|-
| [[GH35]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}3ogv 3ogv]
| β-galactosidase
| ''Hypocrea jecorina''
| 2-phenylethyl 1-thio-β-{{Smallcaps|d}}-galactopyranoside
| Glu200
| Glu298
| <cite>Maksimainen2011</cite>
|-
| [[GH36]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}4fns 4fns]
| β-galactosidase
| ''Geobacillus stearothermophilus''
| 1-deoxy galactonojirimycin
| Asp584
| Asp478
| <cite>Merceron2012</cite>
|-
| [[GH37]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}2jf4 2jf4]
| trehalase
| ''Escherechia coli''
| validoxylamine
| Asp312
| Glu496
| <cite>Gibson2007</cite>
|-
| [[GH38]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}3czn 3czn]
| Golgi α-mannosidase II
| ''Drosophila melanogaster''
| GlcNAcMan(5)GlcNAc(2)
| Asp341
| Asp204
| <cite>Shah2008</cite>
|-
| [[GH39]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| ''anti''
| [{{PDBlink}}2bfg 2bfg]
| β-xylosidase
| ''Geobacillus stearothermophilus''
| 2,5-dinitrophenyl-β-{{Smallcaps|d}}-xyloside
| Glu160
| Glu278
| <cite>Czjzek2005</cite>
|-
| [[GH42]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| ''anti''
| [{{PDBlink}}4ucf 4ucf]
| β-galactosidase
| ''Bifidobacterium bifidum''
| {{Smallcaps|d}}-galactose
| Glu161
| Glu320
| <cite>Godoy2016</cite>
|-
| [[GH43]]
| F
| 5-fold β-propeller
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| inverting
| ''anti''
| [{{PDBlink}}3akh 3akh]
| exo-1,5-α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces avermitilis''
| α-1,5-arabinofuranotriose
| Glu196
| Asp220
| <cite>Fujimoto2010</cite>
|-
| [[GH44]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2eqd 2eqd]
| endoglucanase
| ''Clostridium thermocellum''
| cellooctaose
| Glu186
| Glu359
| <cite>Kitago2007</cite>
|-
| [[GH45]]
| none
| 6-stranded β-barrel
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}4eng 4eng]
| endo-1,4-glucanase
| ''Humicola insolens''
| cellohexaose
| Asp121
| Asp10
| <cite>Davies1996</cite>
|-
| [[GH46]]
| I
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}4olt 4olt]
| chitosanase
| ''Microbacterium sp.'' OU01
| hexa-glucosamine
| Glu25
| Asp43
| <cite>Lyu2014</cite>
|-
| [[GH47]]
| none
| (α/α)7
| alpha-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}1x9d 1x9d]
| α-mannosidase I
| ''Homo sapiens''
| Me-2-S-(α-Man)-2-thio-α-Man
| Asp463
| Glu599
| <cite>Karaveg2005</cite>, <cite>Nerinckx2008</cite>
|-
| [[GH48]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH8''
|
|
|
|
|
|
|-
| [[GH49]]
| N
| β-helix
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH28''
|
|
|
|
|
|
|-
| [[GH50]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}4bq5 4bq5]
| exo-β-agarase
| ''Saccharophagus degradans''
| neoagarotetraose
| Glu535
| Glu695
| <cite>Pluvinage2013</cite>
|-
| [[GH51]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| ''anti''
| [{{PDBlink}}1qw9 1qw9]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Geobacillus stearothermophilus''
| PNP-{{Smallcaps|l}}-arabinofuranoside
| Glu175
| Glu294
| <cite>Hoevel2003</cite>
|-
| [[GH52]]
| O
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}4c1p 4c1p]
| β-xylosidase
| ''Geobacillus thermoglucosidasius''
| xylobiose
| Asp517
| Glu537
| <cite>Espina2014</cite>
|-
| [[GH53]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2ccr 2ccr]
| β-1,4-galactanase
| ''Bacillus licheniformis''
| galactotriose
| Glu165
| Glu263
| <cite>Le_Nours2009</cite>
|-
| [[GH54]]
| none
| β-sandwich
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| ''anti''
| [{{PDBlink}}1wd4 1wd4]
| α-{{Smallcaps|l}}-arabinofuranosidase B
| ''Aspergillus kawachii''
| {{Smallcaps|l}}-arabinofuranose
| Asp297
| Glu221
| <cite>Miyanaga2004</cite>
|-
| [[GH55]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}4tz5 4tz5]
| exo-β-1,3-glucanase
| ''Streptomyces sp.'' SirexAA-E
| laminarihexaose
| Glu502
| unknown
| <cite>Bianchetti2015</cite>
|-
| [[GH56]]
| none
| (β/α)7
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}1fcv 1fcv]
| hyaluronidase
| ''Apis mellifera''
| (hyaluron.)4
| Glu113
| internal
| <cite>Markovic-Housley2000</cite>
|-
| [[GH57]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}1k1y 1k1y]
| glucanotransferase
| ''Thermococcus litoralis''
| acarbose
| Asp214
| Glu123
| <cite>Imamura2003</cite>
|-
| [[GH59]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}4ccc 4ccc]
| β-galactocerebrosidase
| ''Mus musculus''
| PNP-β-{{Smallcaps|d}}-galactoside
| Glu182
| Glu258
| <cite>Hill2013</cite>
|-
| [[GH62]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| unknown
| ''predicted anti by clan''
| ''see at GH43''
|
|
|
|
|
|
|-
| [[GH63]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}5ca3 5ca3]
| α-glucosidase
| ''Escherechia coli''
| glucose and lactose
| Asp501
| Glu727
| <cite>Miyazaki2016</cite>
|-
| [[GH65]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| ''anti''
| [{{PDBlink}}4ktr 4ktr]
| 2-O-α-glucosylglycerol phosphorylase
| ''Bacillus selenitireducens''
| isofagomine
| Glu475
| phosphate
| <cite>Touhara2014</cite>
|-
| [[GH66]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}5axh 5axh]
| dextranase
| ''Thermoanaerobacter pseudethanolicus''
| isomaltohexaose
| Glu374
| Asp312
| <cite>Suzuki2016</cite>
|-
| [[GH67]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}1l8n 1l8n]
| α-glucuronidase
| ''Geobacillus stearothermophilus''
| 4-O-methyl-{{Smallcaps|d}}-glucuronic acid and xylotriose
| Glu286
| Asp364 Glu392
| <cite>Golan2004</cite>
|-
| [[GH68]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}1pt2 1pt2]
| levansucrase
| ''Bacillus subtilis''
| sucrose
| Glu342
| Asp86
| <cite>Meng2003</cite>
|-
| [[GH70]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}3aic 3aic]
| glucansucrase
| ''Streptococcus mutans''
| α-acarbose
| Glu515
| Asp477
| <cite>Ito2011</cite>
|-
| [[GH72]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2w62 2w62]
| β-1,3-glucanotransferase
| ''Saccharomyces cerevisiae'' S288C
| laminaripentaose
| Glu176
| Glu275
| <cite>Hurtado-Gerrero2009</cite>
|-
| [[GH74]]
| none
| 7-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}2ebs 2ebs]
| cellobiohydrolase (OXG-RCBH)
| ''Geotrichum sp.'' m128
| xyloglucan heptasaccharide
| Asp465
| Asp35
| <cite>Yaoi2007</cite>
|-
| [[GH76]]
| none
| (α/α)6
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}5agd 5agd]
| endo-α-1,6-mannanase
| ''Bacillus circulans''
| α-1,6-mannopentaose
| Asp125
| Asp124
| <cite>Thompson2015</cite>
|-
| [[GH77]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2oww 2oww]
| 4-α-glucanotransferase
| ''Thermus thermofilus''
| acarbose + 4-deoxy-α-{{Smallcaps|d}}-glucose
| Glu340
| Asp293
| <cite>Barends2007</cite>
|-
| [[GH78]]
| H
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| ''anti''
| [{{PDBlink}}3w5n 3w5n]
| α-{{Smallcaps|l}}-rhamnosidase
| ''Streptomyces avermitilis''
| {{Smallcaps|l}}-rhamnose
| Glu636
| Glu895
| <cite>Fujimoto2013</cite>
|-
| [[GH79]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}5e9c 5e9c]
| heparanase
| ''Homo sapiens''
| heparin tetrasaccharide
| Glu225
| Glu343
| <cite>Wu2015</cite>
|-
| [[GH80]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH24''
|
|
|
|
|
|
|-
| [[GH81]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}5t4g 5t4g]
| endo-β-1,3-glucanase
| ''Bacillus halodurans'' C-125
| laminarin
| Asp466
| Glu542
| <cite>Pluvinage2017</cite>
|-
| [[GH83]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH33''
|
|
|
|
|
|
|-
| [[GH84]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2chn 2chn]
| β-''N''-acetyl-glucosaminidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| NAG-thiazoline
| Glu242
| internal
| <cite>Dennis2006</cite>
|-
| [[GH85]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2w92 2w92]
| endo-β-''N''-acetyl-glucosaminidase D
| ''Streptococcus pneumoniae'' TIGR4
| NAG-thiazoline
| Glu337
| internal
| <cite>Abbott2009</cite>
|-
| [[GH86]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}4aw7 4aw7]
| β-porphyranase
| ''Bacteroides plebeius''
| porphyran fragment
| Glu152
| Glu279
| <cite>Hehemann_1_2012</cite>
|-
| [[GH89]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2vcb 2vcb]
| α-''N''-acetyl-glucosaminidase
| ''Clostridium perfringens''
| PUGNAc
| Glu483
| Glu601
| <cite>Ficko-Blean2008</cite>
|-
| [[GH92]]
| none
| (α/α)6 and β-sandw.
| alpha-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}2ww1 2ww1]
| α-1,2-mannosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| thiomannobioside
| Glu533
| Asp644 Asp642
| <cite>Zhu2009</cite>
|-
| [[GH93]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|l}}
| retaining
| ''anti''
| [{{PDBlink}}3a72 3a72]
| exo-arabinanase
| ''Penicillium chrysogenum''
| arabinobiose
| Glu246
| Glu174
| <cite>Sogabe2011</cite>
|-
| [[GH94]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}4zli 4zli]
| cellobionic acid phosphorylase
| ''Saccharophagus degradans''
| 3-O-β-{{Smallcaps|d}}-glucopyranosyl-α-{{Smallcaps|d}}-glucopyranuronic acid
| Asp472
| phosphate
| <cite>Nam2015</cite>
|-
| [[GH95]]
| none
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| ''anti''
| [{{PDBlink}}2ead 2ead]
| α-1,2-{{Smallcaps|l}}-fucosidase
| ''Bifidobacterium bifidum''
| Fuc-α-1,2-Gal
| Glu566
| Asn423 Asp766
| <cite>Nagae2007</cite>
|-
| [[GH97]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining + inverting
| ''anti''
| [{{PDBlink}}2zq0 2zq0]
| α-glucosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| acarbose
| Glu532
| Glu508
| <cite>Kitamura2008</cite>
|-
| [[GH98]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}2wmg 2wmg]
| endo-β-1,4-galactosidase
| ''Streptococcus pneumoniae''
| A-LewisY pentasaccharide
| Glu158
| Asp251 Glu301
| <cite>Higgins2009</cite>
|-
| [[GH99]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}4ad4 4ad4]
| endo-α-mannosidase
| ''Bacteroides xylanisolvens''
| glucose-1,3-isofagomine and α-1,2- mannobiose
| Glu336
| debated
| <cite>Thompson2012</cite>
|-
| [[GH100]]
| none
| (α/α)6 core
| beta-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}5gop 5gop]
| invertase
| ''Anabaena (Nostoc) sp.'' pcc7120
| sucrose
| Asp188
| Glu414
| <cite>Xie2016</cite>
|-
| [[GH102]]
| none
| double-ψ β-barrel
| beta-{{Smallcaps|d}}
| retaining
| ''syn''
| [{{PDBlink}}2pi8 2pi8]
| lytic transglycosylase A
| ''Escherichia coli''
| chitohexaose
| Asp308
| none
| <cite>van_Straaten2007</cite>
|-
| [[GH103]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| ''syn''
| [{{PDBlink}}1d0k 1d0k]
| lytic transglycosylase SLT35
| ''Escherichia coli''
| murodipeptides
| Glu162
| internal
| <cite>van_Asselt2000</cite>
|-
| [[GH106]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| inverting
| ''anti''
| [{{PDBlink}}5mwk 5mwk]
| α-{{Smallcaps|l}}-rhamnosidase BT_0986
| ''Bacteroides thetaiotaomicron''
| pectin heptasaccharide
| Glu461
| Glu593 or Glu561
| <cite>Ndeh2017</cite>
|-
| [[GH113]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}4cd8 4cd8]
| β-mannanase
| ''Alicyclobacillus acidocaldarius''
| mannobioimidazole
| Glu151
| Glu231
| <cite>Williams2014</cite>
|-
| [[GH116]]
| O
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at GH52''
|
|
|
|
|
|
|-
| [[GH117]]
| none
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| ''anti''
| [{{PDBlink}}4ak7 4ak7]
| α-1,3-3,6-anhydro-{{Smallcaps|l}}-galactosidase
| ''Bacteroides plebeius''
| neoagarobiose
| His302
| Asp90
| <cite>Hehemann_2_2012</cite>
|-
| [[GH120]]
| none
| parallel β-helix and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}3vsv 3vsv]
| β-xylosidase XylC
| ''Thermoanaerobacterium saccharolyticum'' JW/SL-YS485
| {{Smallcaps|d}}-xylose
| Glu405
| Asp382
| <cite>Huang2012</cite>
|-
| [[GH123]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}5fr0 5fr0]
| exo-β-N-acetyl-galactosaminidase
| ''Clostridium perfringens''
| ''N''-difluoroacetyl-{{Smallcaps|d}}-galactosamine
| Glu345
| internal
| <cite>Noach2016</cite>
|-
| [[GH125]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}5m7y 5m7y]
| exo-α-1,6-mannosidase
| ''Clostridium perfringens''
| 1,6-α-mannotriose
| Asp220
| Glu393
| <cite>Alonso-Gil2016</cite>
|-
| [[GH127]]
| none
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| ''anti''
| [{{PDBlink}}3wrg 3wrg]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bifidobacterium longum''
| {{Smallcaps|l}}-arabinose
| Glu322
| Cys417
| <cite>Huang2014</cite>
|-
| [[GH128]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH1''
|
|
|
|
|
|
|-
| [[GH130]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}5b0s 5b0s]
| β-1,2-mannobiose phosphorylase
| ''Listeria innocua''
| β-1,2-mannotriose
| Asp141-relay
| phosphate
| <cite>Tsuda2015</cite>
|-
| [[GH134]]
| none
| β + α
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}5jug 5jug]
| β-mannanase
| ''Streptomyces sp.''
| mannopentaose
| Glu45
| Asp57
| <cite>Jin2016</cite>
|-
| [[GH137]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|l}}
| unknown
| ''anti''
| [{{PDBlink}}5mui 5mui]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0996
| ''Bacteroides thetaiotaomicron''
| pectin oligosaccharide
| Glu240
| Glu159
| <cite>Ndeh2017</cite>
|-
| [[N. C.]]
| N. C.
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}2vjj 2vjj]
| endo-α-N-acetylglucosaminidase
| Bacteriophage HK620
| O18A1 O-antigen hexasaccharide
| Asp339
| Glu372
| <cite>Barbirz2008</cite>
|}

== References ==

<biblio>
# HeightmanVasella1999 Heightman TD and Vasella AT. ''Recent Insights into Inhibition, Structure, and Mechanism of Configuration-Retaining Glycosidases.'' Angew Chem Int Ed. 1999 38(6):750-770. [http://www3.interscience.wiley.com/journal/55000581/abstract Article online].
# Nerinckx2005 pmid=15642336
# Wu2012 pmid=23137336
# Perez1978 Pérez S and Marchessault RH. ''The exo-anomeric effect: experimental evidence from crystal structures.'' Carbohydr res. 1978 65:114-120. [http://dx.doi.org/10.1016/S0008-6215(00)84218-4 DOI:10.1016/S0008-6215(00)84218-4]
# Cramer1997 Cramer CJ, Truhlar DG, and French AD. ''Exo-anomeric effects on energies and geometries of different conformations of glucose and related systems in the gas phase and aqueous solution.'' Carbohydr res. 1997 298:1-14. [http://dx.doi.org/10.1016/S0008-6215(96)00297-2 DOI:10.1016/S0008-6215(96)00297-2]
# Johnson2009 pmid=19733839
# Alonso2016 pmid=26889578
# Gloster2006 pmid=17002288
# van_Bueren2009 pmid=18976664
# Hrmova2001 pmid=11709165
# Varrot2003 pmid=12595701
# Zhou1999 pmid=10508787
# Sulzenbacher1999 pmid=10200171
# Urbanikova2011 pmid=21501386
# Guerin2002 pmid=11884144
# Schubot2004 pmid=14756552
# Suzuki2009 pmid=19279191
# Wan2014 pmid=24419374
# Sandgren2004 pmid=15364577
# Uitdehaag1999 pmid=10331869
# Miyake2003 pmid=12741813
# Harris1993 pmid=8431441
# Allouch2004 pmid=15062085
# Papanikolau2001 pmid=11560481
# Prag2000 pmid=10884356
# Vocadlo2001 pmid=11518970
# Karlsen1996 pmid=15299731
# Baldwin1993 pmid=8259514
# Cartmell2008 pmid=18799462
# Fernandez-Leiro2010 pmid=20592022
# Abbott2007 pmid=17397864
# Sakurama2012 pmid=22451675
# Sim2008 pmid=18036614
# Verhaest2007 pmid=17335500
# Amaya2004 pmid=15130470
# Zhu2012 pmid=23015718
# Maksimainen2011 pmid=21130883
# Merceron2012 pmid=23012371
# Gibson2007 pmid=17455176
# Shah2008 pmid=18599462
# Czjzek2005 pmid=16212978
# Godoy2016 pmid=27685756
# Fujimoto2010 pmid=20739278
# Kitago2007 pmid=17905739
# Davies1996 pmid=15299721
# Lyu2014 pmid=24766439
# Karaveg2005 pmid=15713668
# Nerinckx2008 pmid=18619586
# Pluvinage2013 pmid=23921382
# Hoevel2003 pmid=14517232
# Espina2014 pmid=24816105
# Le_Nours2009 pmid=19089956
# Miyanaga2004 pmid=15292273
# Bianchetti2015 pmid=25752603
# Markovic-Housley2000 pmid=11080624
# Imamura2003 pmid=12618437
# Hill2013 pmid=24297913
# Miyazaki2016 pmid=27688023
# Touhara2014 pmid=24828502
# Suzuki2016 pmid=26494689
# Golan2004 pmid=14573597
# Meng2003 pmid=14517548
# Ito2011 pmid=21354427
# Hurtado-Gerrero2009 pmid=19097997
# Yaoi2007 pmid=17498741
# Thompson2015 pmid=25772148
# Barends2007 pmid=17420245
# Fujimoto2013 pmid=23486481
# Wu2015 pmid=26575439
# Pluvinage2017 pmid=28781080
# Dennis2006 pmid=16565725
# Abbott2009 pmid=19181667
# Hehemann_1_2012 pmid=23150581
# Ficko-Blean2008 pmid=18443291
# Zhu2009 pmid=20081828
# Sogabe2011 pmid=21543843
# Nam2015 pmid=26041776
# Nagae2007 pmid=17459873
# Kitamura2008 pmid=18981178
# Higgins2009 pmid=19608744
# van_Straaten2007 pmid=17502382
# van_Asselt2000 pmid=10684641
# Ndeh2017 pmid=28329766
# Jin2016 Jin Y, Petricevic M, John A, Raich L, Jenkins H, Portela De Souza L, Cuskin F, Gilbert HJ, Rovira C, Goddard-Borger ED, Williams SJ, and Davies GJ. ''A β-Mannanase with a Lysozyme-like Fold and a Novel Molecular Catalytic Mechanism.'' ACS Cent Sci. 2016 Nov [http://dx.doi.org/10.1021/acscentsci.6b00232 DOI:10.1021/acscentsci.6b00232]
# Ohnuma2014 pmid=24582745
# Thompson2012 pmid=22219371
# Xie2016 pmid=27777307
# Williams2014 pmid=24339341
# Hehemann_2_2012 pmid=22393053
# Huang2012 pmid=22992047
# Noach2016 pmid=27038508
# Alonso-Gil2016 pmid=28026180
# Huang2014 Huang CH, Zhu Z, Cheng YS, Chan HC, Ko TP, Chen CC, Wang I, Ho MR, Hsu ST, Zeng YF, Huang YN, Liu JR, Guo RT. ''Structure and Catalytic Mechanism of a Glycoside Hydrolase Family-127 β-L-Arabinofuranosidase (HypBA1).'' J Bioprocess Biotech. 2014 4:171 [http://dx.doi.org/10.4172/2155-9821.1000171 DOI:10.4172/2155-9821.1000171]
# Tsuda2015 pmid=26632508
# Barbirz2008 pmid=18547389

</biblio>

[[Category:Definitions and explanations]]

Syn/anti lateral protonation

2017-12-23T22:38:34Z

Wim Nerinckx: non-classified glycoside hydrolase pdb-2vjj is an anti protonator

{{CuratorApproved}}
* [[Author]]: ^^^Wim Nerinckx^^^
* [[Responsible Curator]]: ^^^Spencer Williams^^^

----

== Overview ==

This page provides a table that summarizes the spatial positioning of the catalytic [[general acid]] residue in the active sites of [[glycoside hydrolase]]s, relative to the substrate. The table below updates those found in the seminal paper on this concept by Heightman and Vasella <cite>HeightmanVasella1999</cite>, and a following paper by Nerinckx ''et al.'' <cite>Nerinckx2005</cite>.

== Background ==

The ''"not from above, but from the side"'' concept of semi-lateral glycosidic oxygen [[General_acid/base|protonation]] by [[glycoside hydrolase]]s was introduced by Heightman and Vasella <cite>HeightmanVasella1999</cite>. It was originally only described for [[Anomeric centre (alpha and beta)|beta]]-equatorial [[glycoside hydrolase]]s, but appears to be equally applicable to enzymes acting on an [[Anomeric centre (alpha and beta)|alpha]]-axial glycosidic bond <cite>Nerinckx2005</cite>. When dividing [[Sub-site nomenclature|subsite -1]] into half-spaces by a plane defined by the glycosidic oxygen and C1' and H1' of the –1 glycoside, many ligand-complexed structures reveal that the [[General_acid/base|proton donor]] is positioned either in the ''syn'' half-space (near the ring-oxygen of the –1 glycoside), or in the ''anti'' half-space (on the opposite side of the ring-oxygen). Members of the same GH [[Families|family]] appear to share a common ''syn'' or ''anti'' [[General_acid/base|protonator]] arrangement and further, this specificity appears to be preserved within [[Clans|Clans]] of [[Families|families]]. This page's compilation of [[Sub-site nomenclature|subsite -1]] occupied complexes shows that about 70% of all GH [[Families|families]] are ''anti'' [[General_acid/base|protonators]].

Closer inspection of crystal structures of [[Sub-site nomenclature|–1/+1 subsite]]-spanning substrates, or substrate-analogue ligands, in complex with enzymes reveals a further intriguing corollary <cite>Nerinckx2005 Wu2012</cite>. In substrate-bound complexes with ''anti'' [[General_acid/base|protonating]] GH enzymes, the scissile [[Anomeric centre (alpha and beta)|anomeric bond]] (often studied using the thio-analogue) shows a dihedral angle φ (O5'-C1'-[O,S]x-Cx) that is in the lowest-energy synclinal (gauche) conformation. The rationale for this is that a minus synclinal dihedral angle φ for an equatorial glycosidic bond, or plus synclinal for an axial glycosidic bond <cite>Perez1978</cite>, allows for hyperconjugative overlap of the C1'-O5' antibonding orbital with an antiperiplanar-oriented lone pair orbital lobe of the glycosidic oxygen, thereby creating partial double bond character and stabilization of the glycosidic bond by 4–5 kcal/mol; this ground-state stabilizing phenomenon is known as the ‘exo-anomeric effect’ <cite>Cramer1997 Johnson2009 Alonso2016</cite>. ''Anti'' [[General_acid/base|protonation]] occurs on the glycosidic oxygen’s antiperiplanar lone pair, thereby removing the stabilizing exo-anomeric effect. This suggests that ''anti'' [[General_acid/base|protonation]] is an enzymic approach for lowering the activation barrier leading to the [[Transition state|transition state]] (Figure 1 centre).

''Syn'' [[General_acid/base|protonating]] [[glycoside hydrolase]]s apparently make use of a different approach <cite>Nerinckx2005 Wu2012</cite>. In many [[Sub-site nomenclature|–1/+1 subsite]]-spanning ligand complexes, the dihedral angle φ of the scissile anomeric bond has been rotated away from its lowest-energy synclinal position: clockwise to minus-anticlinal or antiperiplanar for beta-equatorial; counterclockwise to plus-anticlinal or antiperiplanar for alpha-axial [[Anomeric centre (alpha and beta)|anomeric bonds]]. This removes the hyperconjugative overlap and thus also the stabilizing exo-anomeric effect. And because of this rotation, a lone pair of the glycosidic oxygen is directed into the ''syn'' half-space, allowing it to be protonated by the ''syn''-positioned [[General_acid/base|proton donor]] (Figure 1 right).

[[File:Syn_anti.jpg|800px|thumb|center|Figure 1. Newman projections, with the glycosidic oxygen as proximal atom and the anomeric carbon as distal atom, showing ''anti'' (centre) versus ''syn'' (right) semi-lateral [[General_acid/base|protonation]] in beta-equatorial (top) and alpha-axial (bottom) [[glycoside hydrolase]]s. The indicated φ is the dihedral angle for O5'-C1'-O4-C4.]]

== Table of ''syn/anti'' protonation examples ==

This table contains only one example per GH [[Families|family]] of a ligand-complexed protein structure where the ''syn'' or ''anti'' positioning of the [[General_acid/base|proton donor]] can be clearly observed; other examples may be available on a [[Families|family-by-family]] basis. The reader is thus advised to consult the [http://www.cazy.org/fam/acc_GH.html#table CAZy database] for a current, comprehensive list of CAZyme structures. Where available, the selected examples are Michaelis-type complexes with the ligand spanning the [[Sub-site nomenclature|-1/+1 subsites]], since these have an intact glycosidic or thioglycosidic bond, or are ''N''-analogs of the substrate (''e.g.'' acarbose). In some examples, the [[General_acid/base|proton donor]] has been mutated (''e.g.'', to the corresponding amide or to an alanine), and in those cases one may wish to look at a superposition of the given PDB example with the structure of the native enzyme. If a Michaelis-type complex is not yet available, the second and third example choices, respectively, are trapped glycosyl-enzyme [[intermediate]]s and product complexes where [[Sub-site nomenclature|subsite -1]] is occupied.

''Please also be aware that this is a large table with many data. Please contact the page Author or Responsible Curator with corrections.''

=== Table ===
This table can be re-sorted by clicking on the icons in the header (''javascript must be turned on in your browser''). To reset the page to be sorted by GH family, click the ''View'' tab at the very top of the page.

{| {{Prettytable}} class="sortable"
|- valign="top"
! '''Family'''
! '''Clan'''
! '''Structure fold '''
! '''Anomeric specificity'''
! '''Mechanism'''
! '''''Syn/anti'' protonator'''
! '''Example PDB ID'''
! '''Enzyme'''
! '''Organism'''
! '''Ligand'''
! '''General acid'''
! '''Nucleophile or General base'''
! '''Reference'''
|-
| [[GH1]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2cer 2cer]
| β-glycosidase S
| ''Sulfolobus solfataricus'' P2
| phenethyl glucoimidazole
| Glu206
| Glu387
| <cite>Gloster2006</cite>
|-
| [[GH2]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| ''anti''
| [{{PDBlink}}2vzu 2vzu]
| exo-β-glucosaminidase
| ''Amicolatopsis orientalis''
| PNP-β-{{Smallcaps|d}}-glucosamine
| Glu469
| Glu541
| <cite>van_Bueren2009</cite>
|-
| [[GH3]]
| none
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| ''anti''
| [{{PDBlink}}1iex 1iex]
| exo-1,3-1,4-glucanase
| ''Hordeum vulgare''
| thiocellobiose
| Glu491
| Asp285
| <cite>Hrmova2001</cite>
|-
| [[GH5]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}1h2j 1h2j]
| endo-β-1,4-glucanase
| ''Bacillus agaradhaerens''
| 2',4'-DNP-2-F-cellobioside
| Glu129
| Glu228
| <cite>Varrot2003</cite>
|-
| [[GH6]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}1qjw 1qjw]
| cellobiohydrolase 2
| ''Hypocrea jecorina''
| (Glc)2-S-(Glc)2
| Asp221
| debated
| <cite>Zhou1999</cite>
|-
| [[GH7]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| ''syn''
| [{{PDBlink}}1ovw 1ovw]
| endo-1,4-glucanase
| ''Fusarium oxysporum''
| thio-(Glc)5
| Glu202
| Glu197
| <cite>Sulzenbacher1999</cite>
|-
| [[GH8]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}1kwf 1kwf]
| endo-1,4-glucanase
| ''Clostridium thermocellum''
| cellopentaose
| Glu95
| Asp278
| <cite>Guerin2002</cite>
|-
| [[GH9]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}1rq5 1rq5]
| cellobiohydrolase
| ''Clostridium thermocellum''
| cellotetraose
| Glu795
| Asp383
| <cite>Schubot2004</cite>
|-
| [[GH10]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2d24 2d24]
| β-1,4-xylanase
| ''Streptomyces olivaceoviridis'' E-86
| xylopentaose
| Glu128
| Glu236
| <cite>Suzuki2009</cite>
|-
| [[GH11]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| ''syn''
| [{{PDBlink}}4hk8 4hk8]
| endo-β-1,4-xylanase
| ''Hypocrea jecorina''
| xylohexaose
| Glu177
| Glu86
| <cite>Wan2014</cite>
|-
| [[GH12]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| ''syn''
| [{{PDBlink}}1w2u 1w2u]
| endoglucanase
| ''Humicola grisea''
| thiocellotetraose
| Glu205
| Glu120
| <cite>Sandgren2004</cite>
|-
| [[GH13]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}1cxk 1cxk]
| β-cyclodextrin glucanotransferase
| ''Bacillus circulans''
| maltononaose
| Glu257
| Asp229
| <cite>Uitdehaag1999</cite>
|-
| [[GH14]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}1itc 1itc]
| β-amylase
| ''Bacillus cereus''
| maltopentaose
| Glu172
| Glu367
| <cite>Miyake2003</cite>
|-
| [[GH15]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}1dog 1dog]
| glucoamylase
| ''Aspergillus awamori''
| 1-deoxynojirimycin
| Glu179
| Glu400
| <cite>Harris1993</cite>
|-
| [[GH16]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| ''syn''
| [{{PDBlink}}1urx 1urx]
| β-agarase A
| ''Zobellia galactanivorans''
| oligoagarose
| Glu152
| Glu147
| <cite>Allouch2004</cite>
|-
| [[GH17]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH1''
|
|
|
|
|
|
|-
| [[GH18]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}1ffr 1ffr]
| chitinase A
| ''Serratia marcescens''
| (NAG)6
| Glu315
| internal
| <cite>Papanikolau2001</cite>
|-
| [[GH19]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}3wh1 3wh1]
| chitinase
| ''Bryum coronatum''
| (GlcNAc)4
| Glu61
| Glu70
| <cite>Ohnuma2014</cite>
|-
| [[GH20]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}1c7s 1c7s]
| chitobiase
| ''Serratia marcescens''
| chitobiose
| Glu540
| internal
| <cite>Prag2000</cite>
|-
| [[GH22]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| ''syn''
| [{{PDBlink}}1h6m 1h6m]
| lysozyme C
| ''Gallus gallus''
| Chit-2-F-chitosyl
| Glu35
| Asp52
| <cite>Vocadlo2001</cite>
|-
| [[GH23]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}1lsp 1lsp]
| lysozyme G
| ''Cygnus atratus''
| Bulgecin A
| Glu73
| internal
| <cite>Karlsen1996</cite>
|-
| [[GH24]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}148l 148l]
| lysozyme E
| Bacteriophage T4
| chitobiosyl
| Glu11
| Glu26
| <cite>Baldwin1993</cite>
|-
| [[GH26]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2vx6 2vx6]
| exo-β-mannanase
| ''Cellvibrio japonicus'' Ueda107
| Gal1Man4
| Glu221
| Glu338
| <cite>Cartmell2008</cite>
|-
| [[GH27]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}} / beta-{{Smallcaps|l}}
| retaining
| ''anti''
| [{{PDBlink}}3lrm 3lrm]
| α-galactosidase
| ''Saccharomyces cerevisiae''
| raffinose
| Asp209
| Asp141
| <cite>Fernandez-Leiro2010</cite>
|-
| [[GH28]]
| N
| β-helix
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| ''anti''
| [{{PDBlink}}2uvf 2uvf]
| exo-polygalacturonosidase
| ''Yersinia enterocolitica'' ATCC9610D
| digalacturonic acid
| Asp402
| Asp381 Asp403
| <cite>Abbott2007</cite>
|-
| [[GH29]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| ''syn''
| [{{PDBlink}}3uet 3uet]
| α-1,3/4-fucosidase
| ''Bifidobacterium longum'' subsp. infantis
| lacto-''N''-fucopentaose II
| Glu217
| Asp172
| <cite>Sakurama2012</cite>
|-
| [[GH30]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2y24 2y24]
| glucurono-xylanase
| ''Dickea chrysanthemi'' D1
| glucuronoxylan tetrasaccharide
| Glu163
| Glu253
| <cite>Urbanikova2011</cite>
|-
| [[GH31]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2qmj 2qmj]
| maltase-glucoamylase
| ''Homo sapiens''
| acarbose
| Asp542
| Asp443
| <cite>Sim2008</cite>
|-
| [[GH32]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2add 2add]
| fructan β-(2,1)-fructosidase
| ''Cichorium intybus''
| sucrose
| Glu201
| Asp22
| <cite>Verhaest2007</cite>
|-
| [[GH33]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}1s0i 1s0i]
| transsialidase
| ''Trypanosoma cruzi''
| sialyllactose
| Asp59
| Tyr342
| <cite>Amaya2004</cite>
|-
| [[GH34]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}4gzw 4gzw]
| N2 neuraminidase
| ''Influenza'' A Tanzania/205/2010 H3N2
| α-{{Smallcaps|d}}-Neup5Ac-(2,3)-β-{{Smallcaps|d}}-Galp-(1,4)-β-{{Smallcaps|d}}-GlcpNAc
| Asp151
| Tyr406
| <cite>Zhu2012</cite>
|-
| [[GH35]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}3ogv 3ogv]
| β-galactosidase
| ''Hypocrea jecorina''
| 2-phenylethyl 1-thio-β-{{Smallcaps|d}}-galactopyranoside
| Glu200
| Glu298
| <cite>Maksimainen2011</cite>
|-
| [[GH36]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}4fns 4fns]
| β-galactosidase
| ''Geobacillus stearothermophilus''
| 1-deoxy galactonojirimycin
| Asp584
| Asp478
| <cite>Merceron2012</cite>
|-
| [[GH37]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}2jf4 2jf4]
| trehalase
| ''Escherechia coli''
| validoxylamine
| Asp312
| Glu496
| <cite>Gibson2007</cite>
|-
| [[GH38]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}3czn 3czn]
| Golgi α-mannosidase II
| ''Drosophila melanogaster''
| GlcNAcMan(5)GlcNAc(2)
| Asp341
| Asp204
| <cite>Shah2008</cite>
|-
| [[GH39]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| ''anti''
| [{{PDBlink}}2bfg 2bfg]
| β-xylosidase
| ''Geobacillus stearothermophilus''
| 2,5-dinitrophenyl-β-{{Smallcaps|d}}-xyloside
| Glu160
| Glu278
| <cite>Czjzek2005</cite>
|-
| [[GH42]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| ''anti''
| [{{PDBlink}}4ucf 4ucf]
| β-galactosidase
| ''Bifidobacterium bifidum''
| {{Smallcaps|d}}-galactose
| Glu161
| Glu320
| <cite>Godoy2016</cite>
|-
| [[GH43]]
| F
| 5-fold β-propeller
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| inverting
| ''anti''
| [{{PDBlink}}3akh 3akh]
| exo-1,5-α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces avermitilis''
| α-1,5-arabinofuranotriose
| Glu196
| Asp220
| <cite>Fujimoto2010</cite>
|-
| [[GH44]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2eqd 2eqd]
| endoglucanase
| ''Clostridium thermocellum''
| cellooctaose
| Glu186
| Glu359
| <cite>Kitago2007</cite>
|-
| [[GH45]]
| none
| 6-stranded β-barrel
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}4eng 4eng]
| endo-1,4-glucanase
| ''Humicola insolens''
| cellohexaose
| Asp121
| Asp10
| <cite>Davies1996</cite>
|-
| [[GH46]]
| I
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}4olt 4olt]
| chitosanase
| ''Microbacterium sp.'' OU01
| hexa-glucosamine
| Glu25
| Asp43
| <cite>Lyu2014</cite>
|-
| [[GH47]]
| none
| (α/α)7
| alpha-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}1x9d 1x9d]
| α-mannosidase I
| ''Homo sapiens''
| Me-2-S-(α-Man)-2-thio-α-Man
| Asp463
| Glu599
| <cite>Karaveg2005</cite>, <cite>Nerinckx2008</cite>
|-
| [[GH48]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH8''
|
|
|
|
|
|
|-
| [[GH49]]
| N
| β-helix
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH28''
|
|
|
|
|
|
|-
| [[GH50]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}4bq5 4bq5]
| exo-β-agarase
| ''Saccharophagus degradans''
| neoagarotetraose
| Glu535
| Glu695
| <cite>Pluvinage2013</cite>
|-
| [[GH51]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| ''anti''
| [{{PDBlink}}1qw9 1qw9]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Geobacillus stearothermophilus''
| PNP-{{Smallcaps|l}}-arabinofuranoside
| Glu175
| Glu294
| <cite>Hoevel2003</cite>
|-
| [[GH52]]
| O
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}4c1p 4c1p]
| β-xylosidase
| ''Geobacillus thermoglucosidasius''
| xylobiose
| Asp517
| Glu537
| <cite>Espina2014</cite>
|-
| [[GH53]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2ccr 2ccr]
| β-1,4-galactanase
| ''Bacillus licheniformis''
| galactotriose
| Glu165
| Glu263
| <cite>Le_Nours2009</cite>
|-
| [[GH54]]
| none
| β-sandwich
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| ''anti''
| [{{PDBlink}}1wd4 1wd4]
| α-{{Smallcaps|l}}-arabinofuranosidase B
| ''Aspergillus kawachii''
| {{Smallcaps|l}}-arabinofuranose
| Asp297
| Glu221
| <cite>Miyanaga2004</cite>
|-
| [[GH55]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}4tz5 4tz5]
| exo-β-1,3-glucanase
| ''Streptomyces sp.'' SirexAA-E
| laminarihexaose
| Glu502
| unknown
| <cite>Bianchetti2015</cite>
|-
| [[GH56]]
| none
| (β/α)7
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}1fcv 1fcv]
| hyaluronidase
| ''Apis mellifera''
| (hyaluron.)4
| Glu113
| internal
| <cite>Markovic-Housley2000</cite>
|-
| [[GH57]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}1k1y 1k1y]
| glucanotransferase
| ''Thermococcus litoralis''
| acarbose
| Asp214
| Glu123
| <cite>Imamura2003</cite>
|-
| [[GH59]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}4ccc 4ccc]
| β-galactocerebrosidase
| ''Mus musculus''
| PNP-β-{{Smallcaps|d}}-galactoside
| Glu182
| Glu258
| <cite>Hill2013</cite>
|-
| [[GH62]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| unknown
| ''predicted anti by clan''
| ''see at GH43''
|
|
|
|
|
|
|-
| [[GH63]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}5ca3 5ca3]
| α-glucosidase
| ''Escherechia coli''
| glucose and lactose
| Asp501
| Glu727
| <cite>Miyazaki2016</cite>
|-
| [[GH65]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| ''anti''
| [{{PDBlink}}4ktr 4ktr]
| 2-O-α-glucosylglycerol phosphorylase
| ''Bacillus selenitireducens''
| isofagomine
| Glu475
| phosphate
| <cite>Touhara2014</cite>
|-
| [[GH66]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}5axh 5axh]
| dextranase
| ''Thermoanaerobacter pseudethanolicus''
| isomaltohexaose
| Glu374
| Asp312
| <cite>Suzuki2016</cite>
|-
| [[GH67]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}1l8n 1l8n]
| α-glucuronidase
| ''Geobacillus stearothermophilus''
| 4-O-methyl-{{Smallcaps|d}}-glucuronic acid and xylotriose
| Glu286
| Asp364 Glu392
| <cite>Golan2004</cite>
|-
| [[GH68]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}1pt2 1pt2]
| levansucrase
| ''Bacillus subtilis''
| sucrose
| Glu342
| Asp86
| <cite>Meng2003</cite>
|-
| [[GH70]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}3aic 3aic]
| glucansucrase
| ''Streptococcus mutans''
| α-acarbose
| Glu515
| Asp477
| <cite>Ito2011</cite>
|-
| [[GH72]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2w62 2w62]
| β-1,3-glucanotransferase
| ''Saccharomyces cerevisiae'' S288C
| laminaripentaose
| Glu176
| Glu275
| <cite>Hurtado-Gerrero2009</cite>
|-
| [[GH74]]
| none
| 7-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}2ebs 2ebs]
| cellobiohydrolase (OXG-RCBH)
| ''Geotrichum sp.'' m128
| xyloglucan heptasaccharide
| Asp465
| Asp35
| <cite>Yaoi2007</cite>
|-
| [[GH76]]
| none
| (α/α)6
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}5agd 5agd]
| endo-α-1,6-mannanase
| ''Bacillus circulans''
| α-1,6-mannopentaose
| Asp125
| Asp124
| <cite>Thompson2015</cite>
|-
| [[GH77]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2oww 2oww]
| 4-α-glucanotransferase
| ''Thermus thermofilus''
| acarbose + 4-deoxy-α-{{Smallcaps|d}}-glucose
| Glu340
| Asp293
| <cite>Barends2007</cite>
|-
| [[GH78]]
| H
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| ''anti''
| [{{PDBlink}}3w5n 3w5n]
| α-{{Smallcaps|l}}-rhamnosidase
| ''Streptomyces avermitilis''
| {{Smallcaps|l}}-rhamnose
| Glu636
| Glu895
| <cite>Fujimoto2013</cite>
|-
| [[GH79]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}5e9c 5e9c]
| heparanase
| ''Homo sapiens''
| heparin tetrasaccharide
| Glu225
| Glu343
| <cite>Wu2015</cite>
|-
| [[GH80]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH24''
|
|
|
|
|
|
|-
| [[GH81]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}5t4g 5t4g]
| endo-β-1,3-glucanase
| ''Bacillus halodurans'' C-125
| laminarin
| Asp466
| Glu542
| <cite>Pluvinage2017</cite>
|-
| [[GH83]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH33''
|
|
|
|
|
|
|-
| [[GH84]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2chn 2chn]
| β-''N''-acetyl-glucosaminidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| NAG-thiazoline
| Glu242
| internal
| <cite>Dennis2006</cite>
|-
| [[GH85]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2w92 2w92]
| endo-β-''N''-acetyl-glucosaminidase D
| ''Streptococcus pneumoniae'' TIGR4
| NAG-thiazoline
| Glu337
| internal
| <cite>Abbott2009</cite>
|-
| [[GH86]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}4aw7 4aw7]
| β-porphyranase
| ''Bacteroides plebeius''
| porphyran fragment
| Glu152
| Glu279
| <cite>Hehemann_1_2012</cite>
|-
| [[GH89]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2vcb 2vcb]
| α-''N''-acetyl-glucosaminidase
| ''Clostridium perfringens''
| PUGNAc
| Glu483
| Glu601
| <cite>Ficko-Blean2008</cite>
|-
| [[GH92]]
| none
| (α/α)6 and β-sandw.
| alpha-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}2ww1 2ww1]
| α-1,2-mannosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| thiomannobioside
| Glu533
| Asp644 Asp642
| <cite>Zhu2009</cite>
|-
| [[GH93]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|l}}
| retaining
| ''anti''
| [{{PDBlink}}3a72 3a72]
| exo-arabinanase
| ''Penicillium chrysogenum''
| arabinobiose
| Glu246
| Glu174
| <cite>Sogabe2011</cite>
|-
| [[GH94]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}4zli 4zli]
| cellobionic acid phosphorylase
| ''Saccharophagus degradans''
| 3-O-β-{{Smallcaps|d}}-glucopyranosyl-α-{{Smallcaps|d}}-glucopyranuronic acid
| Asp472
| phosphate
| <cite>Nam2015</cite>
|-
| [[GH95]]
| none
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| ''anti''
| [{{PDBlink}}2ead 2ead]
| α-1,2-{{Smallcaps|l}}-fucosidase
| ''Bifidobacterium bifidum''
| Fuc-α-1,2-Gal
| Glu566
| Asn423 Asp766
| <cite>Nagae2007</cite>
|-
| [[GH97]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining + inverting
| ''anti''
| [{{PDBlink}}2zq0 2zq0]
| α-glucosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| acarbose
| Glu532
| Glu508
| <cite>Kitamura2008</cite>
|-
| [[GH98]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}2wmg 2wmg]
| endo-β-1,4-galactosidase
| ''Streptococcus pneumoniae''
| A-LewisY pentasaccharide
| Glu158
| Asp251 Glu301
| <cite>Higgins2009</cite>
|-
| [[GH99]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}4ad4 4ad4]
| endo-α-mannosidase
| ''Bacteroides xylanisolvens''
| glucose-1,3-isofagomine and α-1,2- mannobiose
| Glu336
| debated
| <cite>Thompson2012</cite>
|-
| [[GH100]]
| none
| (α/α)6 core
| beta-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}5gop 5gop]
| invertase
| ''Anabaena (Nostoc) sp.'' pcc7120
| sucrose
| Asp188
| Glu414
| <cite>Xie2016</cite>
|-
| [[GH102]]
| none
| double-ψ β-barrel
| beta-{{Smallcaps|d}}
| retaining
| ''syn''
| [{{PDBlink}}2pi8 2pi8]
| lytic transglycosylase A
| ''Escherichia coli''
| chitohexaose
| Asp308
| none
| <cite>van_Straaten2007</cite>
|-
| [[GH103]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| ''syn''
| [{{PDBlink}}1d0k 1d0k]
| lytic transglycosylase SLT35
| ''Escherichia coli''
| murodipeptides
| Glu162
| internal
| <cite>van_Asselt2000</cite>
|-
| [[GH106]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| inverting
| ''anti''
| [{{PDBlink}}5mwk 5mwk]
| α-{{Smallcaps|l}}-rhamnosidase BT_0986
| ''Bacteroides thetaiotaomicron''
| pectin heptasaccharide
| Glu461
| Glu593 or Glu561
| <cite>Ndeh2017</cite>
|-
| [[GH113]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}4cd8 4cd8]
| β-mannanase
| ''Alicyclobacillus acidocaldarius''
| mannobioimidazole
| Glu151
| Glu231
| <cite>Williams2014</cite>
|-
| [[GH116]]
| O
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at GH52''
|
|
|
|
|
|
|-
| [[GH117]]
| none
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| ''anti''
| [{{PDBlink}}4ak7 4ak7]
| α-1,3-3,6-anhydro-{{Smallcaps|l}}-galactosidase
| ''Bacteroides plebeius''
| neoagarobiose
| His302
| Asp90
| <cite>Hehemann_2_2012</cite>
|-
| [[GH120]]
| none
| parallel β-helix and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}3vsv 3vsv]
| β-xylosidase XylC
| ''Thermoanaerobacterium saccharolyticum'' JW/SL-YS485
| {{Smallcaps|d}}-xylose
| Glu405
| Asp382
| <cite>Huang2012</cite>
|-
| [[GH123]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}5fr0 5fr0]
| exo-β-N-acetyl-galactosaminidase
| ''Clostridium perfringens''
| ''N''-difluoroacetyl-{{Smallcaps|d}}-galactosamine
| Glu345
| internal
| <cite>Noach2016</cite>
|-
| [[GH125]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}5m7y 5m7y]
| exo-α-1,6-mannosidase
| ''Clostridium perfringens''
| 1,6-α-mannotriose
| Asp220
| Glu393
| <cite>Alonso-Gil2016</cite>
|-
| [[GH127]]
| none
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| ''anti''
| [{{PDBlink}}3wrg 3wrg]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bifidobacterium longum''
| {{Smallcaps|l}}-arabinose
| Glu322
| Cys417
| <cite>Huang2014</cite>
|-
| [[GH128]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH1''
|
|
|
|
|
|
|-
| [[GH130]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}5b0s 5b0s]
| β-1,2-mannobiose phosphorylase
| ''Listeria innocua''
| β-1,2-mannotriose
| Asp141-relay
| phosphate
| <cite>Tsuda2015</cite>
|-
| [[GH134]]
| none
| β + α
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}5jug 5jug]
| β-mannanase
| ''Streptomyces sp.''
| mannopentaose
| Glu45
| Asp57
| <cite>Jin2016</cite>
|-
| [[GH137]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|l}}
| unknown
| ''anti''
| [{{PDBlink}}5mui 5mui]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0996
| ''Bacteroides thetaiotaomicron''
| pectin oligosaccharide
| Glu240
| Glu159
| <cite>Ndeh2017</cite>
|-
| [[N. C.]]
| N. C.
| parallel β-helix
| alpha-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}2vjj 2vjj]
| endo-α-N-acetylglucosaminidase
| Bacteriophage HK620
| O18A1 O-antigen hexasaccharide
| Asp339
| Glu372
| <cite>Barbirz2008</cite>
|
|}

== References ==

<biblio>
# HeightmanVasella1999 Heightman TD and Vasella AT. ''Recent Insights into Inhibition, Structure, and Mechanism of Configuration-Retaining Glycosidases.'' Angew Chem Int Ed. 1999 38(6):750-770. [http://www3.interscience.wiley.com/journal/55000581/abstract Article online].
# Nerinckx2005 pmid=15642336
# Wu2012 pmid=23137336
# Perez1978 Pérez S and Marchessault RH. ''The exo-anomeric effect: experimental evidence from crystal structures.'' Carbohydr res. 1978 65:114-120. [http://dx.doi.org/10.1016/S0008-6215(00)84218-4 DOI:10.1016/S0008-6215(00)84218-4]
# Cramer1997 Cramer CJ, Truhlar DG, and French AD. ''Exo-anomeric effects on energies and geometries of different conformations of glucose and related systems in the gas phase and aqueous solution.'' Carbohydr res. 1997 298:1-14. [http://dx.doi.org/10.1016/S0008-6215(96)00297-2 DOI:10.1016/S0008-6215(96)00297-2]
# Johnson2009 pmid=19733839
# Alonso2016 pmid=26889578
# Gloster2006 pmid=17002288
# van_Bueren2009 pmid=18976664
# Hrmova2001 pmid=11709165
# Varrot2003 pmid=12595701
# Zhou1999 pmid=10508787
# Sulzenbacher1999 pmid=10200171
# Urbanikova2011 pmid=21501386
# Guerin2002 pmid=11884144
# Schubot2004 pmid=14756552
# Suzuki2009 pmid=19279191
# Wan2014 pmid=24419374
# Sandgren2004 pmid=15364577
# Uitdehaag1999 pmid=10331869
# Miyake2003 pmid=12741813
# Harris1993 pmid=8431441
# Allouch2004 pmid=15062085
# Papanikolau2001 pmid=11560481
# Prag2000 pmid=10884356
# Vocadlo2001 pmid=11518970
# Karlsen1996 pmid=15299731
# Baldwin1993 pmid=8259514
# Cartmell2008 pmid=18799462
# Fernandez-Leiro2010 pmid=20592022
# Abbott2007 pmid=17397864
# Sakurama2012 pmid=22451675
# Sim2008 pmid=18036614
# Verhaest2007 pmid=17335500
# Amaya2004 pmid=15130470
# Zhu2012 pmid=23015718
# Maksimainen2011 pmid=21130883
# Merceron2012 pmid=23012371
# Gibson2007 pmid=17455176
# Shah2008 pmid=18599462
# Czjzek2005 pmid=16212978
# Godoy2016 pmid=27685756
# Fujimoto2010 pmid=20739278
# Kitago2007 pmid=17905739
# Davies1996 pmid=15299721
# Lyu2014 pmid=24766439
# Karaveg2005 pmid=15713668
# Nerinckx2008 pmid=18619586
# Pluvinage2013 pmid=23921382
# Hoevel2003 pmid=14517232
# Espina2014 pmid=24816105
# Le_Nours2009 pmid=19089956
# Miyanaga2004 pmid=15292273
# Bianchetti2015 pmid=25752603
# Markovic-Housley2000 pmid=11080624
# Imamura2003 pmid=12618437
# Hill2013 pmid=24297913
# Miyazaki2016 pmid=27688023
# Touhara2014 pmid=24828502
# Suzuki2016 pmid=26494689
# Golan2004 pmid=14573597
# Meng2003 pmid=14517548
# Ito2011 pmid=21354427
# Hurtado-Gerrero2009 pmid=19097997
# Yaoi2007 pmid=17498741
# Thompson2015 pmid=25772148
# Barends2007 pmid=17420245
# Fujimoto2013 pmid=23486481
# Wu2015 pmid=26575439
# Pluvinage2017 pmid=28781080
# Dennis2006 pmid=16565725
# Abbott2009 pmid=19181667
# Hehemann_1_2012 pmid=23150581
# Ficko-Blean2008 pmid=18443291
# Zhu2009 pmid=20081828
# Sogabe2011 pmid=21543843
# Nam2015 pmid=26041776
# Nagae2007 pmid=17459873
# Kitamura2008 pmid=18981178
# Higgins2009 pmid=19608744
# van_Straaten2007 pmid=17502382
# van_Asselt2000 pmid=10684641
# Ndeh2017 pmid=28329766
# Jin2016 Jin Y, Petricevic M, John A, Raich L, Jenkins H, Portela De Souza L, Cuskin F, Gilbert HJ, Rovira C, Goddard-Borger ED, Williams SJ, and Davies GJ. ''A β-Mannanase with a Lysozyme-like Fold and a Novel Molecular Catalytic Mechanism.'' ACS Cent Sci. 2016 Nov [http://dx.doi.org/10.1021/acscentsci.6b00232 DOI:10.1021/acscentsci.6b00232]
# Ohnuma2014 pmid=24582745
# Thompson2012 pmid=22219371
# Xie2016 pmid=27777307
# Williams2014 pmid=24339341
# Hehemann_2_2012 pmid=22393053
# Huang2012 pmid=22992047
# Noach2016 pmid=27038508
# Alonso-Gil2016 pmid=28026180
# Huang2014 Huang CH, Zhu Z, Cheng YS, Chan HC, Ko TP, Chen CC, Wang I, Ho MR, Hsu ST, Zeng YF, Huang YN, Liu JR, Guo RT. ''Structure and Catalytic Mechanism of a Glycoside Hydrolase Family-127 β-L-Arabinofuranosidase (HypBA1).'' J Bioprocess Biotech. 2014 4:171 [http://dx.doi.org/10.4172/2155-9821.1000171 DOI:10.4172/2155-9821.1000171]
# Tsuda2015 pmid=26632508
# Barbirz2008 pmid=18547389

</biblio>

[[Category:Definitions and explanations]]

Syn/anti lateral protonation

2017-12-16T21:15:09Z

Wim Nerinckx: GH81 is syn

{{CuratorApproved}}
* [[Author]]: ^^^Wim Nerinckx^^^
* [[Responsible Curator]]: ^^^Spencer Williams^^^

----

== Overview ==

This page provides a table that summarizes the spatial positioning of the catalytic [[general acid]] residue in the active sites of [[glycoside hydrolase]]s, relative to the substrate. The table below updates those found in the seminal paper on this concept by Heightman and Vasella <cite>HeightmanVasella1999</cite>, and a following paper by Nerinckx ''et al.'' <cite>Nerinckx2005</cite>.

== Background ==

The ''"not from above, but from the side"'' concept of semi-lateral glycosidic oxygen [[General_acid/base|protonation]] by [[glycoside hydrolase]]s was introduced by Heightman and Vasella <cite>HeightmanVasella1999</cite>. It was originally only described for [[Anomeric centre (alpha and beta)|beta]]-equatorial [[glycoside hydrolase]]s, but appears to be equally applicable to enzymes acting on an [[Anomeric centre (alpha and beta)|alpha]]-axial glycosidic bond <cite>Nerinckx2005</cite>. When dividing [[Sub-site nomenclature|subsite -1]] into half-spaces by a plane defined by the glycosidic oxygen and C1' and H1' of the –1 glycoside, many ligand-complexed structures reveal that the [[General_acid/base|proton donor]] is positioned either in the ''syn'' half-space (near the ring-oxygen of the –1 glycoside), or in the ''anti'' half-space (on the opposite side of the ring-oxygen). Members of the same GH [[Families|family]] appear to share a common ''syn'' or ''anti'' [[General_acid/base|protonator]] arrangement and further, this specificity appears to be preserved within [[Clans|Clans]] of [[Families|families]]. This page's compilation of [[Sub-site nomenclature|subsite -1]] occupied complexes shows that about 70% of all GH [[Families|families]] are ''anti'' [[General_acid/base|protonators]].

Closer inspection of crystal structures of [[Sub-site nomenclature|–1/+1 subsite]]-spanning substrates, or substrate-analogue ligands, in complex with enzymes reveals a further intriguing corollary <cite>Nerinckx2005 Wu2012</cite>. In substrate-bound complexes with ''anti'' [[General_acid/base|protonating]] GH enzymes, the scissile [[Anomeric centre (alpha and beta)|anomeric bond]] (often studied using the thio-analogue) shows a dihedral angle φ (O5'-C1'-[O,S]x-Cx) that is in the lowest-energy synclinal (gauche) conformation. The rationale for this is that a minus synclinal dihedral angle φ for an equatorial glycosidic bond, or plus synclinal for an axial glycosidic bond <cite>Perez1978</cite>, allows for hyperconjugative overlap of the C1'-O5' antibonding orbital with an antiperiplanar-oriented lone pair orbital lobe of the glycosidic oxygen, thereby creating partial double bond character and stabilization of the glycosidic bond by 4–5 kcal/mol; this ground-state stabilizing phenomenon is known as the ‘exo-anomeric effect’ <cite>Cramer1997 Johnson2009 Alonso2016</cite>. ''Anti'' [[General_acid/base|protonation]] occurs on the glycosidic oxygen’s antiperiplanar lone pair, thereby removing the stabilizing exo-anomeric effect. This suggests that ''anti'' [[General_acid/base|protonation]] is an enzymic approach for lowering the activation barrier leading to the [[Transition state|transition state]] (Figure 1 centre).

''Syn'' [[General_acid/base|protonating]] [[glycoside hydrolase]]s apparently make use of a different approach <cite>Nerinckx2005 Wu2012</cite>. In many [[Sub-site nomenclature|–1/+1 subsite]]-spanning ligand complexes, the dihedral angle φ of the scissile anomeric bond has been rotated away from its lowest-energy synclinal position: clockwise to minus-anticlinal or antiperiplanar for beta-equatorial; counterclockwise to plus-anticlinal or antiperiplanar for alpha-axial [[Anomeric centre (alpha and beta)|anomeric bonds]]. This removes the hyperconjugative overlap and thus also the stabilizing exo-anomeric effect. And because of this rotation, a lone pair of the glycosidic oxygen is directed into the ''syn'' half-space, allowing it to be protonated by the ''syn''-positioned [[General_acid/base|proton donor]] (Figure 1 right).

[[File:Syn_anti.jpg|800px|thumb|center|Figure 1. Newman projections, with the glycosidic oxygen as proximal atom and the anomeric carbon as distal atom, showing ''anti'' (centre) versus ''syn'' (right) semi-lateral [[General_acid/base|protonation]] in beta-equatorial (top) and alpha-axial (bottom) [[glycoside hydrolase]]s. The indicated φ is the dihedral angle for O5'-C1'-O4-C4.]]

== Table of ''syn/anti'' protonation examples ==

This table contains only one example per GH [[Families|family]] of a ligand-complexed protein structure where the ''syn'' or ''anti'' positioning of the [[General_acid/base|proton donor]] can be clearly observed; other examples may be available on a [[Families|family-by-family]] basis. The reader is thus advised to consult the [http://www.cazy.org/fam/acc_GH.html#table CAZy database] for a current, comprehensive list of CAZyme structures. Where available, the selected examples are Michaelis-type complexes with the ligand spanning the [[Sub-site nomenclature|-1/+1 subsites]], since these have an intact glycosidic or thioglycosidic bond, or are ''N''-analogs of the substrate (''e.g.'' acarbose). In some examples, the [[General_acid/base|proton donor]] has been mutated (''e.g.'', to the corresponding amide or to an alanine), and in those cases one may wish to look at a superposition of the given PDB example with the structure of the native enzyme. If a Michaelis-type complex is not yet available, the second and third example choices, respectively, are trapped glycosyl-enzyme [[intermediate]]s and product complexes where [[Sub-site nomenclature|subsite -1]] is occupied.

''Please also be aware that this is a large table with many data. Please contact the page Author or Responsible Curator with corrections.''

=== Table ===
This table can be re-sorted by clicking on the icons in the header (''javascript must be turned on in your browser''). To reset the page to be sorted by GH family, click the ''View'' tab at the very top of the page.

{| {{Prettytable}} class="sortable"
|- valign="top"
! '''Family'''
! '''Clan'''
! '''Structure fold '''
! '''Anomeric specificity'''
! '''Mechanism'''
! '''''Syn/anti'' protonator'''
! '''Example PDB ID'''
! '''Enzyme'''
! '''Organism'''
! '''Ligand'''
! '''General acid'''
! '''Nucleophile or General base'''
! '''Reference'''
|-
| [[GH1]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2cer 2cer]
| β-glycosidase S
| ''Sulfolobus solfataricus'' P2
| phenethyl glucoimidazole
| Glu206
| Glu387
| <cite>Gloster2006</cite>
|-
| [[GH2]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| ''anti''
| [{{PDBlink}}2vzu 2vzu]
| exo-β-glucosaminidase
| ''Amicolatopsis orientalis''
| PNP-β-{{Smallcaps|d}}-glucosamine
| Glu469
| Glu541
| <cite>van_Bueren2009</cite>
|-
| [[GH3]]
| none
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| ''anti''
| [{{PDBlink}}1iex 1iex]
| exo-1,3-1,4-glucanase
| ''Hordeum vulgare''
| thiocellobiose
| Glu491
| Asp285
| <cite>Hrmova2001</cite>
|-
| [[GH5]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}1h2j 1h2j]
| endo-β-1,4-glucanase
| ''Bacillus agaradhaerens''
| 2',4'-DNP-2-F-cellobioside
| Glu129
| Glu228
| <cite>Varrot2003</cite>
|-
| [[GH6]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}1qjw 1qjw]
| cellobiohydrolase 2
| ''Hypocrea jecorina''
| (Glc)2-S-(Glc)2
| Asp221
| debated
| <cite>Zhou1999</cite>
|-
| [[GH7]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| ''syn''
| [{{PDBlink}}1ovw 1ovw]
| endo-1,4-glucanase
| ''Fusarium oxysporum''
| thio-(Glc)5
| Glu202
| Glu197
| <cite>Sulzenbacher1999</cite>
|-
| [[GH8]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}1kwf 1kwf]
| endo-1,4-glucanase
| ''Clostridium thermocellum''
| cellopentaose
| Glu95
| Asp278
| <cite>Guerin2002</cite>
|-
| [[GH9]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}1rq5 1rq5]
| cellobiohydrolase
| ''Clostridium thermocellum''
| cellotetraose
| Glu795
| Asp383
| <cite>Schubot2004</cite>
|-
| [[GH10]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2d24 2d24]
| β-1,4-xylanase
| ''Streptomyces olivaceoviridis'' E-86
| xylopentaose
| Glu128
| Glu236
| <cite>Suzuki2009</cite>
|-
| [[GH11]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| ''syn''
| [{{PDBlink}}4hk8 4hk8]
| endo-β-1,4-xylanase
| ''Hypocrea jecorina''
| xylohexaose
| Glu177
| Glu86
| <cite>Wan2014</cite>
|-
| [[GH12]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| ''syn''
| [{{PDBlink}}1w2u 1w2u]
| endoglucanase
| ''Humicola grisea''
| thiocellotetraose
| Glu205
| Glu120
| <cite>Sandgren2004</cite>
|-
| [[GH13]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}1cxk 1cxk]
| β-cyclodextrin glucanotransferase
| ''Bacillus circulans''
| maltononaose
| Glu257
| Asp229
| <cite>Uitdehaag1999</cite>
|-
| [[GH14]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}1itc 1itc]
| β-amylase
| ''Bacillus cereus''
| maltopentaose
| Glu172
| Glu367
| <cite>Miyake2003</cite>
|-
| [[GH15]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}1dog 1dog]
| glucoamylase
| ''Aspergillus awamori''
| 1-deoxynojirimycin
| Glu179
| Glu400
| <cite>Harris1993</cite>
|-
| [[GH16]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| ''syn''
| [{{PDBlink}}1urx 1urx]
| β-agarase A
| ''Zobellia galactanivorans''
| oligoagarose
| Glu152
| Glu147
| <cite>Allouch2004</cite>
|-
| [[GH17]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH1''
|
|
|
|
|
|
|-
| [[GH18]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}1ffr 1ffr]
| chitinase A
| ''Serratia marcescens''
| (NAG)6
| Glu315
| internal
| <cite>Papanikolau2001</cite>
|-
| [[GH19]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}3wh1 3wh1]
| chitinase
| ''Bryum coronatum''
| (GlcNAc)4
| Glu61
| Glu70
| <cite>Ohnuma2014</cite>
|-
| [[GH20]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}1c7s 1c7s]
| chitobiase
| ''Serratia marcescens''
| chitobiose
| Glu540
| internal
| <cite>Prag2000</cite>
|-
| [[GH22]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| ''syn''
| [{{PDBlink}}1h6m 1h6m]
| lysozyme C
| ''Gallus gallus''
| Chit-2-F-chitosyl
| Glu35
| Asp52
| <cite>Vocadlo2001</cite>
|-
| [[GH23]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}1lsp 1lsp]
| lysozyme G
| ''Cygnus atratus''
| Bulgecin A
| Glu73
| internal
| <cite>Karlsen1996</cite>
|-
| [[GH24]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}148l 148l]
| lysozyme E
| Bacteriophage T4
| chitobiosyl
| Glu11
| Glu26
| <cite>Baldwin1993</cite>
|-
| [[GH26]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2vx6 2vx6]
| exo-β-mannanase
| ''Cellvibrio japonicus'' Ueda107
| Gal1Man4
| Glu221
| Glu338
| <cite>Cartmell2008</cite>
|-
| [[GH27]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}} / beta-{{Smallcaps|l}}
| retaining
| ''anti''
| [{{PDBlink}}3lrm 3lrm]
| α-galactosidase
| ''Saccharomyces cerevisiae''
| raffinose
| Asp209
| Asp141
| <cite>Fernandez-Leiro2010</cite>
|-
| [[GH28]]
| N
| β-helix
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| ''anti''
| [{{PDBlink}}2uvf 2uvf]
| exo-polygalacturonosidase
| ''Yersinia enterocolitica'' ATCC9610D
| digalacturonic acid
| Asp402
| Asp381 Asp403
| <cite>Abbott2007</cite>
|-
| [[GH29]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| ''syn''
| [{{PDBlink}}3uet 3uet]
| α-1,3/4-fucosidase
| ''Bifidobacterium longum'' subsp. infantis
| lacto-''N''-fucopentaose II
| Glu217
| Asp172
| <cite>Sakurama2012</cite>
|-
| [[GH30]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2y24 2y24]
| glucurono-xylanase
| ''Dickea chrysanthemi'' D1
| glucuronoxylan tetrasaccharide
| Glu163
| Glu253
| <cite>Urbanikova2011</cite>
|-
| [[GH31]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2qmj 2qmj]
| maltase-glucoamylase
| ''Homo sapiens''
| acarbose
| Asp542
| Asp443
| <cite>Sim2008</cite>
|-
| [[GH32]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2add 2add]
| fructan β-(2,1)-fructosidase
| ''Cichorium intybus''
| sucrose
| Glu201
| Asp22
| <cite>Verhaest2007</cite>
|-
| [[GH33]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}1s0i 1s0i]
| transsialidase
| ''Trypanosoma cruzi''
| sialyllactose
| Asp59
| Tyr342
| <cite>Amaya2004</cite>
|-
| [[GH34]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}4gzw 4gzw]
| N2 neuraminidase
| ''Influenza'' A Tanzania/205/2010 H3N2
| α-{{Smallcaps|d}}-Neup5Ac-(2,3)-β-{{Smallcaps|d}}-Galp-(1,4)-β-{{Smallcaps|d}}-GlcpNAc
| Asp151
| Tyr406
| <cite>Zhu2012</cite>
|-
| [[GH35]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}3ogv 3ogv]
| β-galactosidase
| ''Hypocrea jecorina''
| 2-phenylethyl 1-thio-β-{{Smallcaps|d}}-galactopyranoside
| Glu200
| Glu298
| <cite>Maksimainen2011</cite>
|-
| [[GH36]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}4fns 4fns]
| β-galactosidase
| ''Geobacillus stearothermophilus''
| 1-deoxy galactonojirimycin
| Asp584
| Asp478
| <cite>Merceron2012</cite>
|-
| [[GH37]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}2jf4 2jf4]
| trehalase
| ''Escherechia coli''
| validoxylamine
| Asp312
| Glu496
| <cite>Gibson2007</cite>
|-
| [[GH38]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}3czn 3czn]
| Golgi α-mannosidase II
| ''Drosophila melanogaster''
| GlcNAcMan(5)GlcNAc(2)
| Asp341
| Asp204
| <cite>Shah2008</cite>
|-
| [[GH39]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| ''anti''
| [{{PDBlink}}2bfg 2bfg]
| β-xylosidase
| ''Geobacillus stearothermophilus''
| 2,5-dinitrophenyl-β-{{Smallcaps|d}}-xyloside
| Glu160
| Glu278
| <cite>Czjzek2005</cite>
|-
| [[GH42]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| ''anti''
| [{{PDBlink}}4ucf 4ucf]
| β-galactosidase
| ''Bifidobacterium bifidum''
| {{Smallcaps|d}}-galactose
| Glu161
| Glu320
| <cite>Godoy2016</cite>
|-
| [[GH43]]
| F
| 5-fold β-propeller
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| inverting
| ''anti''
| [{{PDBlink}}3akh 3akh]
| exo-1,5-α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces avermitilis''
| α-1,5-arabinofuranotriose
| Glu196
| Asp220
| <cite>Fujimoto2010</cite>
|-
| [[GH44]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2eqd 2eqd]
| endoglucanase
| ''Clostridium thermocellum''
| cellooctaose
| Glu186
| Glu359
| <cite>Kitago2007</cite>
|-
| [[GH45]]
| none
| 6-stranded β-barrel
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}4eng 4eng]
| endo-1,4-glucanase
| ''Humicola insolens''
| cellohexaose
| Asp121
| Asp10
| <cite>Davies1996</cite>
|-
| [[GH46]]
| I
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}4olt 4olt]
| chitosanase
| ''Microbacterium sp.'' OU01
| hexa-glucosamine
| Glu25
| Asp43
| <cite>Lyu2014</cite>
|-
| [[GH47]]
| none
| (α/α)7
| alpha-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}1x9d 1x9d]
| α-mannosidase I
| ''Homo sapiens''
| Me-2-S-(α-Man)-2-thio-α-Man
| Asp463
| Glu599
| <cite>Karaveg2005</cite>, <cite>Nerinckx2008</cite>
|-
| [[GH48]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH8''
|
|
|
|
|
|
|-
| [[GH49]]
| N
| β-helix
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH28''
|
|
|
|
|
|
|-
| [[GH50]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}4bq5 4bq5]
| exo-β-agarase
| ''Saccharophagus degradans''
| neoagarotetraose
| Glu535
| Glu695
| <cite>Pluvinage2013</cite>
|-
| [[GH51]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| ''anti''
| [{{PDBlink}}1qw9 1qw9]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Geobacillus stearothermophilus''
| PNP-{{Smallcaps|l}}-arabinofuranoside
| Glu175
| Glu294
| <cite>Hoevel2003</cite>
|-
| [[GH52]]
| O
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}4c1p 4c1p]
| β-xylosidase
| ''Geobacillus thermoglucosidasius''
| xylobiose
| Asp517
| Glu537
| <cite>Espina2014</cite>
|-
| [[GH53]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2ccr 2ccr]
| β-1,4-galactanase
| ''Bacillus licheniformis''
| galactotriose
| Glu165
| Glu263
| <cite>Le_Nours2009</cite>
|-
| [[GH54]]
| none
| β-sandwich
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| ''anti''
| [{{PDBlink}}1wd4 1wd4]
| α-{{Smallcaps|l}}-arabinofuranosidase B
| ''Aspergillus kawachii''
| {{Smallcaps|l}}-arabinofuranose
| Asp297
| Glu221
| <cite>Miyanaga2004</cite>
|-
| [[GH55]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}4tz5 4tz5]
| exo-β-1,3-glucanase
| ''Streptomyces sp.'' SirexAA-E
| laminarihexaose
| Glu502
| unknown
| <cite>Bianchetti2015</cite>
|-
| [[GH56]]
| none
| (β/α)7
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}1fcv 1fcv]
| hyaluronidase
| ''Apis mellifera''
| (hyaluron.)4
| Glu113
| internal
| <cite>Markovic-Housley2000</cite>
|-
| [[GH57]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}1k1y 1k1y]
| glucanotransferase
| ''Thermococcus litoralis''
| acarbose
| Asp214
| Glu123
| <cite>Imamura2003</cite>
|-
| [[GH59]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}4ccc 4ccc]
| β-galactocerebrosidase
| ''Mus musculus''
| PNP-β-{{Smallcaps|d}}-galactoside
| Glu182
| Glu258
| <cite>Hill2013</cite>
|-
| [[GH62]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| unknown
| ''predicted anti by clan''
| ''see at GH43''
|
|
|
|
|
|
|-
| [[GH63]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}5ca3 5ca3]
| α-glucosidase
| ''Escherechia coli''
| glucose and lactose
| Asp501
| Glu727
| <cite>Miyazaki2016</cite>
|-
| [[GH65]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| ''anti''
| [{{PDBlink}}4ktr 4ktr]
| 2-O-α-glucosylglycerol phosphorylase
| ''Bacillus selenitireducens''
| isofagomine
| Glu475
| phosphate
| <cite>Touhara2014</cite>
|-
| [[GH66]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}5axh 5axh]
| dextranase
| ''Thermoanaerobacter pseudethanolicus''
| isomaltohexaose
| Glu374
| Asp312
| <cite>Suzuki2016</cite>
|-
| [[GH67]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}1l8n 1l8n]
| α-glucuronidase
| ''Geobacillus stearothermophilus''
| 4-O-methyl-{{Smallcaps|d}}-glucuronic acid and xylotriose
| Glu286
| Asp364 Glu392
| <cite>Golan2004</cite>
|-
| [[GH68]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}1pt2 1pt2]
| levansucrase
| ''Bacillus subtilis''
| sucrose
| Glu342
| Asp86
| <cite>Meng2003</cite>
|-
| [[GH70]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}3aic 3aic]
| glucansucrase
| ''Streptococcus mutans''
| α-acarbose
| Glu515
| Asp477
| <cite>Ito2011</cite>
|-
| [[GH72]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2w62 2w62]
| β-1,3-glucanotransferase
| ''Saccharomyces cerevisiae'' S288C
| laminaripentaose
| Glu176
| Glu275
| <cite>Hurtado-Gerrero2009</cite>
|-
| [[GH74]]
| none
| 7-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}2ebs 2ebs]
| cellobiohydrolase (OXG-RCBH)
| ''Geotrichum sp.'' m128
| xyloglucan heptasaccharide
| Asp465
| Asp35
| <cite>Yaoi2007</cite>
|-
| [[GH76]]
| none
| (α/α)6
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}5agd 5agd]
| endo-α-1,6-mannanase
| ''Bacillus circulans''
| α-1,6-mannopentaose
| Asp125
| Asp124
| <cite>Thompson2015</cite>
|-
| [[GH77]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2oww 2oww]
| 4-α-glucanotransferase
| ''Thermus thermofilus''
| acarbose + 4-deoxy-α-{{Smallcaps|d}}-glucose
| Glu340
| Asp293
| <cite>Barends2007</cite>
|-
| [[GH78]]
| H
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| ''anti''
| [{{PDBlink}}3w5n 3w5n]
| α-{{Smallcaps|l}}-rhamnosidase
| ''Streptomyces avermitilis''
| {{Smallcaps|l}}-rhamnose
| Glu636
| Glu895
| <cite>Fujimoto2013</cite>
|-
| [[GH79]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}5e9c 5e9c]
| heparanase
| ''Homo sapiens''
| heparin tetrasaccharide
| Glu225
| Glu343
| <cite>Wu2015</cite>
|-
| [[GH80]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH24''
|
|
|
|
|
|
|-
| [[GH81]]
| none
| β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}5t4g 5t4g]
| endo-β-1,3-glucanase
| ''Bacillus halodurans'' C-125
| laminarin
| Asp466
| Glu542
| <cite>Pluvinage2017</cite>
|-
| [[GH83]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH33''
|
|
|
|
|
|
|-
| [[GH84]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2chn 2chn]
| β-''N''-acetyl-glucosaminidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| NAG-thiazoline
| Glu242
| internal
| <cite>Dennis2006</cite>
|-
| [[GH85]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2w92 2w92]
| endo-β-''N''-acetyl-glucosaminidase D
| ''Streptococcus pneumoniae'' TIGR4
| NAG-thiazoline
| Glu337
| internal
| <cite>Abbott2009</cite>
|-
| [[GH86]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}4aw7 4aw7]
| β-porphyranase
| ''Bacteroides plebeius''
| porphyran fragment
| Glu152
| Glu279
| <cite>Hehemann_1_2012</cite>
|-
| [[GH89]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2vcb 2vcb]
| α-''N''-acetyl-glucosaminidase
| ''Clostridium perfringens''
| PUGNAc
| Glu483
| Glu601
| <cite>Ficko-Blean2008</cite>
|-
| [[GH92]]
| none
| (α/α)6 and β-sandw.
| alpha-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}2ww1 2ww1]
| α-1,2-mannosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| thiomannobioside
| Glu533
| Asp644 Asp642
| <cite>Zhu2009</cite>
|-
| [[GH93]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|l}}
| retaining
| ''anti''
| [{{PDBlink}}3a72 3a72]
| exo-arabinanase
| ''Penicillium chrysogenum''
| arabinobiose
| Glu246
| Glu174
| <cite>Sogabe2011</cite>
|-
| [[GH94]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}4zli 4zli]
| cellobionic acid phosphorylase
| ''Saccharophagus degradans''
| 3-O-β-{{Smallcaps|d}}-glucopyranosyl-α-{{Smallcaps|d}}-glucopyranuronic acid
| Asp472
| phosphate
| <cite>Nam2015</cite>
|-
| [[GH95]]
| none
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| ''anti''
| [{{PDBlink}}2ead 2ead]
| α-1,2-{{Smallcaps|l}}-fucosidase
| ''Bifidobacterium bifidum''
| Fuc-α-1,2-Gal
| Glu566
| Asn423 Asp766
| <cite>Nagae2007</cite>
|-
| [[GH97]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining + inverting
| ''anti''
| [{{PDBlink}}2zq0 2zq0]
| α-glucosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| acarbose
| Glu532
| Glu508
| <cite>Kitamura2008</cite>
|-
| [[GH98]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}2wmg 2wmg]
| endo-β-1,4-galactosidase
| ''Streptococcus pneumoniae''
| A-LewisY pentasaccharide
| Glu158
| Asp251 Glu301
| <cite>Higgins2009</cite>
|-
| [[GH99]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}4ad4 4ad4]
| endo-α-mannosidase
| ''Bacteroides xylanisolvens''
| glucose-1,3-isofagomine and α-1,2- mannobiose
| Glu336
| debated
| <cite>Thompson2012</cite>
|-
| [[GH100]]
| none
| (α/α)6 core
| beta-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}5gop 5gop]
| invertase
| ''Anabaena (Nostoc) sp.'' pcc7120
| sucrose
| Asp188
| Glu414
| <cite>Xie2016</cite>
|-
| [[GH102]]
| none
| double-ψ β-barrel
| beta-{{Smallcaps|d}}
| retaining
| ''syn''
| [{{PDBlink}}2pi8 2pi8]
| lytic transglycosylase A
| ''Escherichia coli''
| chitohexaose
| Asp308
| none
| <cite>van_Straaten2007</cite>
|-
| [[GH103]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| ''syn''
| [{{PDBlink}}1d0k 1d0k]
| lytic transglycosylase SLT35
| ''Escherichia coli''
| murodipeptides
| Glu162
| internal
| <cite>van_Asselt2000</cite>
|-
| [[GH106]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| inverting
| ''anti''
| [{{PDBlink}}5mwk 5mwk]
| α-{{Smallcaps|l}}-rhamnosidase BT_0986
| ''Bacteroides thetaiotaomicron''
| pectin heptasaccharide
| Glu461
| Glu593 or Glu561
| <cite>Ndeh2017</cite>
|-
| [[GH113]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}4cd8 4cd8]
| β-mannanase
| ''Alicyclobacillus acidocaldarius''
| mannobioimidazole
| Glu151
| Glu231
| <cite>Williams2014</cite>
|-
| [[GH116]]
| O
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at GH52''
|
|
|
|
|
|
|-
| [[GH117]]
| none
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| ''anti''
| [{{PDBlink}}4ak7 4ak7]
| α-1,3-3,6-anhydro-{{Smallcaps|l}}-galactosidase
| ''Bacteroides plebeius''
| neoagarobiose
| His302
| Asp90
| <cite>Hehemann_2_2012</cite>
|-
| [[GH120]]
| none
| parallel β-helix and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}3vsv 3vsv]
| β-xylosidase XylC
| ''Thermoanaerobacterium saccharolyticum'' JW/SL-YS485
| {{Smallcaps|d}}-xylose
| Glu405
| Asp382
| <cite>Huang2012</cite>
|-
| [[GH123]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}5fr0 5fr0]
| exo-β-N-acetyl-galactosaminidase
| ''Clostridium perfringens''
| ''N''-difluoroacetyl-{{Smallcaps|d}}-galactosamine
| Glu345
| internal
| <cite>Noach2016</cite>
|-
| [[GH125]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}5m7y 5m7y]
| exo-α-1,6-mannosidase
| ''Clostridium perfringens''
| 1,6-α-mannotriose
| Asp220
| Glu393
| <cite>Alonso-Gil2016</cite>
|-
| [[GH127]]
| none
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| ''anti''
| [{{PDBlink}}3wrg 3wrg]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bifidobacterium longum''
| {{Smallcaps|l}}-arabinose
| Glu322
| Cys417
| <cite>Huang2014</cite>
|-
| [[GH128]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH1''
|
|
|
|
|
|
|-
| [[GH130]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}5b0s 5b0s]
| β-1,2-mannobiose phosphorylase
| ''Listeria innocua''
| β-1,2-mannotriose
| Asp141-relay
| phosphate
| <cite>Tsuda2015</cite>
|-
| [[GH134]]
| none
| β + α
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}5jug 5jug]
| β-mannanase
| ''Streptomyces sp.''
| mannopentaose
| Glu45
| Asp57
| <cite>Jin2016</cite>
|-
| [[GH137]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|l}}
| unknown
| ''anti''
| [{{PDBlink}}5mui 5mui]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0996
| ''Bacteroides thetaiotaomicron''
| pectin oligosaccharide
| Glu240
| Glu159
| <cite>Ndeh2017</cite>
|
|}

== References ==

<biblio>
# HeightmanVasella1999 Heightman TD and Vasella AT. ''Recent Insights into Inhibition, Structure, and Mechanism of Configuration-Retaining Glycosidases.'' Angew Chem Int Ed. 1999 38(6):750-770. [http://www3.interscience.wiley.com/journal/55000581/abstract Article online].
# Nerinckx2005 pmid=15642336
# Wu2012 pmid=23137336
# Perez1978 Pérez S and Marchessault RH. ''The exo-anomeric effect: experimental evidence from crystal structures.'' Carbohydr res. 1978 65:114-120. [http://dx.doi.org/10.1016/S0008-6215(00)84218-4 DOI:10.1016/S0008-6215(00)84218-4]
# Cramer1997 Cramer CJ, Truhlar DG, and French AD. ''Exo-anomeric effects on energies and geometries of different conformations of glucose and related systems in the gas phase and aqueous solution.'' Carbohydr res. 1997 298:1-14. [http://dx.doi.org/10.1016/S0008-6215(96)00297-2 DOI:10.1016/S0008-6215(96)00297-2]
# Johnson2009 pmid=19733839
# Alonso2016 pmid=26889578
# Gloster2006 pmid=17002288
# van_Bueren2009 pmid=18976664
# Hrmova2001 pmid=11709165
# Varrot2003 pmid=12595701
# Zhou1999 pmid=10508787
# Sulzenbacher1999 pmid=10200171
# Urbanikova2011 pmid=21501386
# Guerin2002 pmid=11884144
# Schubot2004 pmid=14756552
# Suzuki2009 pmid=19279191
# Wan2014 pmid=24419374
# Sandgren2004 pmid=15364577
# Uitdehaag1999 pmid=10331869
# Miyake2003 pmid=12741813
# Harris1993 pmid=8431441
# Allouch2004 pmid=15062085
# Papanikolau2001 pmid=11560481
# Prag2000 pmid=10884356
# Vocadlo2001 pmid=11518970
# Karlsen1996 pmid=15299731
# Baldwin1993 pmid=8259514
# Cartmell2008 pmid=18799462
# Fernandez-Leiro2010 pmid=20592022
# Abbott2007 pmid=17397864
# Sakurama2012 pmid=22451675
# Sim2008 pmid=18036614
# Verhaest2007 pmid=17335500
# Amaya2004 pmid=15130470
# Zhu2012 pmid=23015718
# Maksimainen2011 pmid=21130883
# Merceron2012 pmid=23012371
# Gibson2007 pmid=17455176
# Shah2008 pmid=18599462
# Czjzek2005 pmid=16212978
# Godoy2016 pmid=27685756
# Fujimoto2010 pmid=20739278
# Kitago2007 pmid=17905739
# Davies1996 pmid=15299721
# Lyu2014 pmid=24766439
# Karaveg2005 pmid=15713668
# Nerinckx2008 pmid=18619586
# Pluvinage2013 pmid=23921382
# Hoevel2003 pmid=14517232
# Espina2014 pmid=24816105
# Le_Nours2009 pmid=19089956
# Miyanaga2004 pmid=15292273
# Bianchetti2015 pmid=25752603
# Markovic-Housley2000 pmid=11080624
# Imamura2003 pmid=12618437
# Hill2013 pmid=24297913
# Miyazaki2016 pmid=27688023
# Touhara2014 pmid=24828502
# Suzuki2016 pmid=26494689
# Golan2004 pmid=14573597
# Meng2003 pmid=14517548
# Ito2011 pmid=21354427
# Hurtado-Gerrero2009 pmid=19097997
# Yaoi2007 pmid=17498741
# Thompson2015 pmid=25772148
# Barends2007 pmid=17420245
# Fujimoto2013 pmid=23486481
# Wu2015 pmid=26575439
# Pluvinage2017 pmid=28781080
# Dennis2006 pmid=16565725
# Abbott2009 pmid=19181667
# Hehemann_1_2012 pmid=23150581
# Ficko-Blean2008 pmid=18443291
# Zhu2009 pmid=20081828
# Sogabe2011 pmid=21543843
# Nam2015 pmid=26041776
# Nagae2007 pmid=17459873
# Kitamura2008 pmid=18981178
# Higgins2009 pmid=19608744
# van_Straaten2007 pmid=17502382
# van_Asselt2000 pmid=10684641
# Ndeh2017 pmid=28329766
# Jin2016 Jin Y, Petricevic M, John A, Raich L, Jenkins H, Portela De Souza L, Cuskin F, Gilbert HJ, Rovira C, Goddard-Borger ED, Williams SJ, and Davies GJ. ''A β-Mannanase with a Lysozyme-like Fold and a Novel Molecular Catalytic Mechanism.'' ACS Cent Sci. 2016 Nov [http://dx.doi.org/10.1021/acscentsci.6b00232 DOI:10.1021/acscentsci.6b00232]
# Ohnuma2014 pmid=24582745
# Thompson2012 pmid=22219371
# Xie2016 pmid=27777307
# Williams2014 pmid=24339341
# Hehemann_2_2012 pmid=22393053
# Huang2012 pmid=22992047
# Noach2016 pmid=27038508
# Alonso-Gil2016 pmid=28026180
# Huang2014 Huang CH, Zhu Z, Cheng YS, Chan HC, Ko TP, Chen CC, Wang I, Ho MR, Hsu ST, Zeng YF, Huang YN, Liu JR, Guo RT. ''Structure and Catalytic Mechanism of a Glycoside Hydrolase Family-127 β-L-Arabinofuranosidase (HypBA1).'' J Bioprocess Biotech. 2014 4:171 [http://dx.doi.org/10.4172/2155-9821.1000171 DOI:10.4172/2155-9821.1000171]
# Tsuda2015 pmid=26632508

</biblio>

[[Category:Definitions and explanations]]

Syn/anti lateral protonation

2017-12-16T21:07:10Z

Wim Nerinckx: GH77 better anti example

{{CuratorApproved}}
* [[Author]]: ^^^Wim Nerinckx^^^
* [[Responsible Curator]]: ^^^Spencer Williams^^^

----

== Overview ==

This page provides a table that summarizes the spatial positioning of the catalytic [[general acid]] residue in the active sites of [[glycoside hydrolase]]s, relative to the substrate. The table below updates those found in the seminal paper on this concept by Heightman and Vasella <cite>HeightmanVasella1999</cite>, and a following paper by Nerinckx ''et al.'' <cite>Nerinckx2005</cite>.

== Background ==

The ''"not from above, but from the side"'' concept of semi-lateral glycosidic oxygen [[General_acid/base|protonation]] by [[glycoside hydrolase]]s was introduced by Heightman and Vasella <cite>HeightmanVasella1999</cite>. It was originally only described for [[Anomeric centre (alpha and beta)|beta]]-equatorial [[glycoside hydrolase]]s, but appears to be equally applicable to enzymes acting on an [[Anomeric centre (alpha and beta)|alpha]]-axial glycosidic bond <cite>Nerinckx2005</cite>. When dividing [[Sub-site nomenclature|subsite -1]] into half-spaces by a plane defined by the glycosidic oxygen and C1' and H1' of the –1 glycoside, many ligand-complexed structures reveal that the [[General_acid/base|proton donor]] is positioned either in the ''syn'' half-space (near the ring-oxygen of the –1 glycoside), or in the ''anti'' half-space (on the opposite side of the ring-oxygen). Members of the same GH [[Families|family]] appear to share a common ''syn'' or ''anti'' [[General_acid/base|protonator]] arrangement and further, this specificity appears to be preserved within [[Clans|Clans]] of [[Families|families]]. This page's compilation of [[Sub-site nomenclature|subsite -1]] occupied complexes shows that about 70% of all GH [[Families|families]] are ''anti'' [[General_acid/base|protonators]].

Closer inspection of crystal structures of [[Sub-site nomenclature|–1/+1 subsite]]-spanning substrates, or substrate-analogue ligands, in complex with enzymes reveals a further intriguing corollary <cite>Nerinckx2005 Wu2012</cite>. In substrate-bound complexes with ''anti'' [[General_acid/base|protonating]] GH enzymes, the scissile [[Anomeric centre (alpha and beta)|anomeric bond]] (often studied using the thio-analogue) shows a dihedral angle φ (O5'-C1'-[O,S]x-Cx) that is in the lowest-energy synclinal (gauche) conformation. The rationale for this is that a minus synclinal dihedral angle φ for an equatorial glycosidic bond, or plus synclinal for an axial glycosidic bond <cite>Perez1978</cite>, allows for hyperconjugative overlap of the C1'-O5' antibonding orbital with an antiperiplanar-oriented lone pair orbital lobe of the glycosidic oxygen, thereby creating partial double bond character and stabilization of the glycosidic bond by 4–5 kcal/mol; this ground-state stabilizing phenomenon is known as the ‘exo-anomeric effect’ <cite>Cramer1997 Johnson2009 Alonso2016</cite>. ''Anti'' [[General_acid/base|protonation]] occurs on the glycosidic oxygen’s antiperiplanar lone pair, thereby removing the stabilizing exo-anomeric effect. This suggests that ''anti'' [[General_acid/base|protonation]] is an enzymic approach for lowering the activation barrier leading to the [[Transition state|transition state]] (Figure 1 centre).

''Syn'' [[General_acid/base|protonating]] [[glycoside hydrolase]]s apparently make use of a different approach <cite>Nerinckx2005 Wu2012</cite>. In many [[Sub-site nomenclature|–1/+1 subsite]]-spanning ligand complexes, the dihedral angle φ of the scissile anomeric bond has been rotated away from its lowest-energy synclinal position: clockwise to minus-anticlinal or antiperiplanar for beta-equatorial; counterclockwise to plus-anticlinal or antiperiplanar for alpha-axial [[Anomeric centre (alpha and beta)|anomeric bonds]]. This removes the hyperconjugative overlap and thus also the stabilizing exo-anomeric effect. And because of this rotation, a lone pair of the glycosidic oxygen is directed into the ''syn'' half-space, allowing it to be protonated by the ''syn''-positioned [[General_acid/base|proton donor]] (Figure 1 right).

[[File:Syn_anti.jpg|800px|thumb|center|Figure 1. Newman projections, with the glycosidic oxygen as proximal atom and the anomeric carbon as distal atom, showing ''anti'' (centre) versus ''syn'' (right) semi-lateral [[General_acid/base|protonation]] in beta-equatorial (top) and alpha-axial (bottom) [[glycoside hydrolase]]s. The indicated φ is the dihedral angle for O5'-C1'-O4-C4.]]

== Table of ''syn/anti'' protonation examples ==

This table contains only one example per GH [[Families|family]] of a ligand-complexed protein structure where the ''syn'' or ''anti'' positioning of the [[General_acid/base|proton donor]] can be clearly observed; other examples may be available on a [[Families|family-by-family]] basis. The reader is thus advised to consult the [http://www.cazy.org/fam/acc_GH.html#table CAZy database] for a current, comprehensive list of CAZyme structures. Where available, the selected examples are Michaelis-type complexes with the ligand spanning the [[Sub-site nomenclature|-1/+1 subsites]], since these have an intact glycosidic or thioglycosidic bond, or are ''N''-analogs of the substrate (''e.g.'' acarbose). In some examples, the [[General_acid/base|proton donor]] has been mutated (''e.g.'', to the corresponding amide or to an alanine), and in those cases one may wish to look at a superposition of the given PDB example with the structure of the native enzyme. If a Michaelis-type complex is not yet available, the second and third example choices, respectively, are trapped glycosyl-enzyme [[intermediate]]s and product complexes where [[Sub-site nomenclature|subsite -1]] is occupied.

''Please also be aware that this is a large table with many data. Please contact the page Author or Responsible Curator with corrections.''

=== Table ===
This table can be re-sorted by clicking on the icons in the header (''javascript must be turned on in your browser''). To reset the page to be sorted by GH family, click the ''View'' tab at the very top of the page.

{| {{Prettytable}} class="sortable"
|- valign="top"
! '''Family'''
! '''Clan'''
! '''Structure fold '''
! '''Anomeric specificity'''
! '''Mechanism'''
! '''''Syn/anti'' protonator'''
! '''Example PDB ID'''
! '''Enzyme'''
! '''Organism'''
! '''Ligand'''
! '''General acid'''
! '''Nucleophile or General base'''
! '''Reference'''
|-
| [[GH1]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2cer 2cer]
| β-glycosidase S
| ''Sulfolobus solfataricus'' P2
| phenethyl glucoimidazole
| Glu206
| Glu387
| <cite>Gloster2006</cite>
|-
| [[GH2]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| ''anti''
| [{{PDBlink}}2vzu 2vzu]
| exo-β-glucosaminidase
| ''Amicolatopsis orientalis''
| PNP-β-{{Smallcaps|d}}-glucosamine
| Glu469
| Glu541
| <cite>van_Bueren2009</cite>
|-
| [[GH3]]
| none
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| ''anti''
| [{{PDBlink}}1iex 1iex]
| exo-1,3-1,4-glucanase
| ''Hordeum vulgare''
| thiocellobiose
| Glu491
| Asp285
| <cite>Hrmova2001</cite>
|-
| [[GH5]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}1h2j 1h2j]
| endo-β-1,4-glucanase
| ''Bacillus agaradhaerens''
| 2',4'-DNP-2-F-cellobioside
| Glu129
| Glu228
| <cite>Varrot2003</cite>
|-
| [[GH6]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}1qjw 1qjw]
| cellobiohydrolase 2
| ''Hypocrea jecorina''
| (Glc)2-S-(Glc)2
| Asp221
| debated
| <cite>Zhou1999</cite>
|-
| [[GH7]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| ''syn''
| [{{PDBlink}}1ovw 1ovw]
| endo-1,4-glucanase
| ''Fusarium oxysporum''
| thio-(Glc)5
| Glu202
| Glu197
| <cite>Sulzenbacher1999</cite>
|-
| [[GH8]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}1kwf 1kwf]
| endo-1,4-glucanase
| ''Clostridium thermocellum''
| cellopentaose
| Glu95
| Asp278
| <cite>Guerin2002</cite>
|-
| [[GH9]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}1rq5 1rq5]
| cellobiohydrolase
| ''Clostridium thermocellum''
| cellotetraose
| Glu795
| Asp383
| <cite>Schubot2004</cite>
|-
| [[GH10]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2d24 2d24]
| β-1,4-xylanase
| ''Streptomyces olivaceoviridis'' E-86
| xylopentaose
| Glu128
| Glu236
| <cite>Suzuki2009</cite>
|-
| [[GH11]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| ''syn''
| [{{PDBlink}}4hk8 4hk8]
| endo-β-1,4-xylanase
| ''Hypocrea jecorina''
| xylohexaose
| Glu177
| Glu86
| <cite>Wan2014</cite>
|-
| [[GH12]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| ''syn''
| [{{PDBlink}}1w2u 1w2u]
| endoglucanase
| ''Humicola grisea''
| thiocellotetraose
| Glu205
| Glu120
| <cite>Sandgren2004</cite>
|-
| [[GH13]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}1cxk 1cxk]
| β-cyclodextrin glucanotransferase
| ''Bacillus circulans''
| maltononaose
| Glu257
| Asp229
| <cite>Uitdehaag1999</cite>
|-
| [[GH14]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}1itc 1itc]
| β-amylase
| ''Bacillus cereus''
| maltopentaose
| Glu172
| Glu367
| <cite>Miyake2003</cite>
|-
| [[GH15]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}1dog 1dog]
| glucoamylase
| ''Aspergillus awamori''
| 1-deoxynojirimycin
| Glu179
| Glu400
| <cite>Harris1993</cite>
|-
| [[GH16]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| ''syn''
| [{{PDBlink}}1urx 1urx]
| β-agarase A
| ''Zobellia galactanivorans''
| oligoagarose
| Glu152
| Glu147
| <cite>Allouch2004</cite>
|-
| [[GH17]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH1''
|
|
|
|
|
|
|-
| [[GH18]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}1ffr 1ffr]
| chitinase A
| ''Serratia marcescens''
| (NAG)6
| Glu315
| internal
| <cite>Papanikolau2001</cite>
|-
| [[GH19]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}3wh1 3wh1]
| chitinase
| ''Bryum coronatum''
| (GlcNAc)4
| Glu61
| Glu70
| <cite>Ohnuma2014</cite>
|-
| [[GH20]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}1c7s 1c7s]
| chitobiase
| ''Serratia marcescens''
| chitobiose
| Glu540
| internal
| <cite>Prag2000</cite>
|-
| [[GH22]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| ''syn''
| [{{PDBlink}}1h6m 1h6m]
| lysozyme C
| ''Gallus gallus''
| Chit-2-F-chitosyl
| Glu35
| Asp52
| <cite>Vocadlo2001</cite>
|-
| [[GH23]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}1lsp 1lsp]
| lysozyme G
| ''Cygnus atratus''
| Bulgecin A
| Glu73
| internal
| <cite>Karlsen1996</cite>
|-
| [[GH24]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}148l 148l]
| lysozyme E
| Bacteriophage T4
| chitobiosyl
| Glu11
| Glu26
| <cite>Baldwin1993</cite>
|-
| [[GH26]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2vx6 2vx6]
| exo-β-mannanase
| ''Cellvibrio japonicus'' Ueda107
| Gal1Man4
| Glu221
| Glu338
| <cite>Cartmell2008</cite>
|-
| [[GH27]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}} / beta-{{Smallcaps|l}}
| retaining
| ''anti''
| [{{PDBlink}}3lrm 3lrm]
| α-galactosidase
| ''Saccharomyces cerevisiae''
| raffinose
| Asp209
| Asp141
| <cite>Fernandez-Leiro2010</cite>
|-
| [[GH28]]
| N
| β-helix
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| ''anti''
| [{{PDBlink}}2uvf 2uvf]
| exo-polygalacturonosidase
| ''Yersinia enterocolitica'' ATCC9610D
| digalacturonic acid
| Asp402
| Asp381 Asp403
| <cite>Abbott2007</cite>
|-
| [[GH29]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| ''syn''
| [{{PDBlink}}3uet 3uet]
| α-1,3/4-fucosidase
| ''Bifidobacterium longum'' subsp. infantis
| lacto-''N''-fucopentaose II
| Glu217
| Asp172
| <cite>Sakurama2012</cite>
|-
| [[GH30]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2y24 2y24]
| glucurono-xylanase
| ''Dickea chrysanthemi'' D1
| glucuronoxylan tetrasaccharide
| Glu163
| Glu253
| <cite>Urbanikova2011</cite>
|-
| [[GH31]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2qmj 2qmj]
| maltase-glucoamylase
| ''Homo sapiens''
| acarbose
| Asp542
| Asp443
| <cite>Sim2008</cite>
|-
| [[GH32]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2add 2add]
| fructan β-(2,1)-fructosidase
| ''Cichorium intybus''
| sucrose
| Glu201
| Asp22
| <cite>Verhaest2007</cite>
|-
| [[GH33]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}1s0i 1s0i]
| transsialidase
| ''Trypanosoma cruzi''
| sialyllactose
| Asp59
| Tyr342
| <cite>Amaya2004</cite>
|-
| [[GH34]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}4gzw 4gzw]
| N2 neuraminidase
| ''Influenza'' A Tanzania/205/2010 H3N2
| α-{{Smallcaps|d}}-Neup5Ac-(2,3)-β-{{Smallcaps|d}}-Galp-(1,4)-β-{{Smallcaps|d}}-GlcpNAc
| Asp151
| Tyr406
| <cite>Zhu2012</cite>
|-
| [[GH35]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}3ogv 3ogv]
| β-galactosidase
| ''Hypocrea jecorina''
| 2-phenylethyl 1-thio-β-{{Smallcaps|d}}-galactopyranoside
| Glu200
| Glu298
| <cite>Maksimainen2011</cite>
|-
| [[GH36]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}4fns 4fns]
| β-galactosidase
| ''Geobacillus stearothermophilus''
| 1-deoxy galactonojirimycin
| Asp584
| Asp478
| <cite>Merceron2012</cite>
|-
| [[GH37]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}2jf4 2jf4]
| trehalase
| ''Escherechia coli''
| validoxylamine
| Asp312
| Glu496
| <cite>Gibson2007</cite>
|-
| [[GH38]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}3czn 3czn]
| Golgi α-mannosidase II
| ''Drosophila melanogaster''
| GlcNAcMan(5)GlcNAc(2)
| Asp341
| Asp204
| <cite>Shah2008</cite>
|-
| [[GH39]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| ''anti''
| [{{PDBlink}}2bfg 2bfg]
| β-xylosidase
| ''Geobacillus stearothermophilus''
| 2,5-dinitrophenyl-β-{{Smallcaps|d}}-xyloside
| Glu160
| Glu278
| <cite>Czjzek2005</cite>
|-
| [[GH42]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| ''anti''
| [{{PDBlink}}4ucf 4ucf]
| β-galactosidase
| ''Bifidobacterium bifidum''
| {{Smallcaps|d}}-galactose
| Glu161
| Glu320
| <cite>Godoy2016</cite>
|-
| [[GH43]]
| F
| 5-fold β-propeller
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| inverting
| ''anti''
| [{{PDBlink}}3akh 3akh]
| exo-1,5-α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces avermitilis''
| α-1,5-arabinofuranotriose
| Glu196
| Asp220
| <cite>Fujimoto2010</cite>
|-
| [[GH44]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2eqd 2eqd]
| endoglucanase
| ''Clostridium thermocellum''
| cellooctaose
| Glu186
| Glu359
| <cite>Kitago2007</cite>
|-
| [[GH45]]
| none
| 6-stranded β-barrel
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}4eng 4eng]
| endo-1,4-glucanase
| ''Humicola insolens''
| cellohexaose
| Asp121
| Asp10
| <cite>Davies1996</cite>
|-
| [[GH46]]
| I
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}4olt 4olt]
| chitosanase
| ''Microbacterium sp.'' OU01
| hexa-glucosamine
| Glu25
| Asp43
| <cite>Lyu2014</cite>
|-
| [[GH47]]
| none
| (α/α)7
| alpha-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}1x9d 1x9d]
| α-mannosidase I
| ''Homo sapiens''
| Me-2-S-(α-Man)-2-thio-α-Man
| Asp463
| Glu599
| <cite>Karaveg2005</cite>, <cite>Nerinckx2008</cite>
|-
| [[GH48]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH8''
|
|
|
|
|
|
|-
| [[GH49]]
| N
| β-helix
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH28''
|
|
|
|
|
|
|-
| [[GH50]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}4bq5 4bq5]
| exo-β-agarase
| ''Saccharophagus degradans''
| neoagarotetraose
| Glu535
| Glu695
| <cite>Pluvinage2013</cite>
|-
| [[GH51]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| ''anti''
| [{{PDBlink}}1qw9 1qw9]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Geobacillus stearothermophilus''
| PNP-{{Smallcaps|l}}-arabinofuranoside
| Glu175
| Glu294
| <cite>Hoevel2003</cite>
|-
| [[GH52]]
| O
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}4c1p 4c1p]
| β-xylosidase
| ''Geobacillus thermoglucosidasius''
| xylobiose
| Asp517
| Glu537
| <cite>Espina2014</cite>
|-
| [[GH53]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2ccr 2ccr]
| β-1,4-galactanase
| ''Bacillus licheniformis''
| galactotriose
| Glu165
| Glu263
| <cite>Le_Nours2009</cite>
|-
| [[GH54]]
| none
| β-sandwich
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| ''anti''
| [{{PDBlink}}1wd4 1wd4]
| α-{{Smallcaps|l}}-arabinofuranosidase B
| ''Aspergillus kawachii''
| {{Smallcaps|l}}-arabinofuranose
| Asp297
| Glu221
| <cite>Miyanaga2004</cite>
|-
| [[GH55]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}4tz5 4tz5]
| exo-β-1,3-glucanase
| ''Streptomyces sp.'' SirexAA-E
| laminarihexaose
| Glu502
| unknown
| <cite>Bianchetti2015</cite>
|-
| [[GH56]]
| none
| (β/α)7
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}1fcv 1fcv]
| hyaluronidase
| ''Apis mellifera''
| (hyaluron.)4
| Glu113
| internal
| <cite>Markovic-Housley2000</cite>
|-
| [[GH57]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}1k1y 1k1y]
| glucanotransferase
| ''Thermococcus litoralis''
| acarbose
| Asp214
| Glu123
| <cite>Imamura2003</cite>
|-
| [[GH59]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}4ccc 4ccc]
| β-galactocerebrosidase
| ''Mus musculus''
| PNP-β-{{Smallcaps|d}}-galactoside
| Glu182
| Glu258
| <cite>Hill2013</cite>
|-
| [[GH62]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| unknown
| ''predicted anti by clan''
| ''see at GH43''
|
|
|
|
|
|
|-
| [[GH63]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}5ca3 5ca3]
| α-glucosidase
| ''Escherechia coli''
| glucose and lactose
| Asp501
| Glu727
| <cite>Miyazaki2016</cite>
|-
| [[GH65]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| ''anti''
| [{{PDBlink}}4ktr 4ktr]
| 2-O-α-glucosylglycerol phosphorylase
| ''Bacillus selenitireducens''
| isofagomine
| Glu475
| phosphate
| <cite>Touhara2014</cite>
|-
| [[GH66]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}5axh 5axh]
| dextranase
| ''Thermoanaerobacter pseudethanolicus''
| isomaltohexaose
| Glu374
| Asp312
| <cite>Suzuki2016</cite>
|-
| [[GH67]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}1l8n 1l8n]
| α-glucuronidase
| ''Geobacillus stearothermophilus''
| 4-O-methyl-{{Smallcaps|d}}-glucuronic acid and xylotriose
| Glu286
| Asp364 Glu392
| <cite>Golan2004</cite>
|-
| [[GH68]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}1pt2 1pt2]
| levansucrase
| ''Bacillus subtilis''
| sucrose
| Glu342
| Asp86
| <cite>Meng2003</cite>
|-
| [[GH70]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}3aic 3aic]
| glucansucrase
| ''Streptococcus mutans''
| α-acarbose
| Glu515
| Asp477
| <cite>Ito2011</cite>
|-
| [[GH72]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2w62 2w62]
| β-1,3-glucanotransferase
| ''Saccharomyces cerevisiae'' S288C
| laminaripentaose
| Glu176
| Glu275
| <cite>Hurtado-Gerrero2009</cite>
|-
| [[GH74]]
| none
| 7-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}2ebs 2ebs]
| cellobiohydrolase (OXG-RCBH)
| ''Geotrichum sp.'' m128
| xyloglucan heptasaccharide
| Asp465
| Asp35
| <cite>Yaoi2007</cite>
|-
| [[GH76]]
| none
| (α/α)6
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}5agd 5agd]
| endo-α-1,6-mannanase
| ''Bacillus circulans''
| α-1,6-mannopentaose
| Asp125
| Asp124
| <cite>Thompson2015</cite>
|-
| [[GH77]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2oww 2oww]
| 4-α-glucanotransferase
| ''Thermus thermofilus''
| acarbose + 4-deoxy-α-{{Smallcaps|d}}-glucose
| Glu340
| Asp293
| <cite>Barends2007</cite>
|-
| [[GH78]]
| H
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| ''anti''
| [{{PDBlink}}3w5n 3w5n]
| α-{{Smallcaps|l}}-rhamnosidase
| ''Streptomyces avermitilis''
| {{Smallcaps|l}}-rhamnose
| Glu636
| Glu895
| <cite>Fujimoto2013</cite>
|-
| [[GH79]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}5e9c 5e9c]
| heparanase
| ''Homo sapiens''
| heparin tetrasaccharide
| Glu225
| Glu343
| <cite>Wu2015</cite>
|-
| [[GH80]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH24''
|
|
|
|
|
|
|-
| [[GH83]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH33''
|
|
|
|
|
|
|-
| [[GH84]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2chn 2chn]
| β-''N''-acetyl-glucosaminidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| NAG-thiazoline
| Glu242
| internal
| <cite>Dennis2006</cite>
|-
| [[GH85]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2w92 2w92]
| endo-β-''N''-acetyl-glucosaminidase D
| ''Streptococcus pneumoniae'' TIGR4
| NAG-thiazoline
| Glu337
| internal
| <cite>Abbott2009</cite>
|-
| [[GH86]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}4aw7 4aw7]
| β-porphyranase
| ''Bacteroides plebeius''
| porphyran fragment
| Glu152
| Glu279
| <cite>Hehemann_1_2012</cite>
|-
| [[GH89]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2vcb 2vcb]
| α-''N''-acetyl-glucosaminidase
| ''Clostridium perfringens''
| PUGNAc
| Glu483
| Glu601
| <cite>Ficko-Blean2008</cite>
|-
| [[GH92]]
| none
| (α/α)6 and β-sandw.
| alpha-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}2ww1 2ww1]
| α-1,2-mannosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| thiomannobioside
| Glu533
| Asp644 Asp642
| <cite>Zhu2009</cite>
|-
| [[GH93]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|l}}
| retaining
| ''anti''
| [{{PDBlink}}3a72 3a72]
| exo-arabinanase
| ''Penicillium chrysogenum''
| arabinobiose
| Glu246
| Glu174
| <cite>Sogabe2011</cite>
|-
| [[GH94]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}4zli 4zli]
| cellobionic acid phosphorylase
| ''Saccharophagus degradans''
| 3-O-β-{{Smallcaps|d}}-glucopyranosyl-α-{{Smallcaps|d}}-glucopyranuronic acid
| Asp472
| phosphate
| <cite>Nam2015</cite>
|-
| [[GH95]]
| none
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| ''anti''
| [{{PDBlink}}2ead 2ead]
| α-1,2-{{Smallcaps|l}}-fucosidase
| ''Bifidobacterium bifidum''
| Fuc-α-1,2-Gal
| Glu566
| Asn423 Asp766
| <cite>Nagae2007</cite>
|-
| [[GH97]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining + inverting
| ''anti''
| [{{PDBlink}}2zq0 2zq0]
| α-glucosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| acarbose
| Glu532
| Glu508
| <cite>Kitamura2008</cite>
|-
| [[GH98]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}2wmg 2wmg]
| endo-β-1,4-galactosidase
| ''Streptococcus pneumoniae''
| A-LewisY pentasaccharide
| Glu158
| Asp251 Glu301
| <cite>Higgins2009</cite>
|-
| [[GH99]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}4ad4 4ad4]
| endo-α-mannosidase
| ''Bacteroides xylanisolvens''
| glucose-1,3-isofagomine and α-1,2- mannobiose
| Glu336
| debated
| <cite>Thompson2012</cite>
|-
| [[GH100]]
| none
| (α/α)6 core
| beta-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}5gop 5gop]
| invertase
| ''Anabaena (Nostoc) sp.'' pcc7120
| sucrose
| Asp188
| Glu414
| <cite>Xie2016</cite>
|-
| [[GH102]]
| none
| double-ψ β-barrel
| beta-{{Smallcaps|d}}
| retaining
| ''syn''
| [{{PDBlink}}2pi8 2pi8]
| lytic transglycosylase A
| ''Escherichia coli''
| chitohexaose
| Asp308
| none
| <cite>van_Straaten2007</cite>
|-
| [[GH103]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| ''syn''
| [{{PDBlink}}1d0k 1d0k]
| lytic transglycosylase SLT35
| ''Escherichia coli''
| murodipeptides
| Glu162
| internal
| <cite>van_Asselt2000</cite>
|-
| [[GH106]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| inverting
| ''anti''
| [{{PDBlink}}5mwk 5mwk]
| α-{{Smallcaps|l}}-rhamnosidase BT_0986
| ''Bacteroides thetaiotaomicron''
| pectin heptasaccharide
| Glu461
| Glu593 or Glu561
| <cite>Ndeh2017</cite>
|-
| [[GH113]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}4cd8 4cd8]
| β-mannanase
| ''Alicyclobacillus acidocaldarius''
| mannobioimidazole
| Glu151
| Glu231
| <cite>Williams2014</cite>
|-
| [[GH116]]
| O
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at GH52''
|
|
|
|
|
|
|-
| [[GH117]]
| none
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| ''anti''
| [{{PDBlink}}4ak7 4ak7]
| α-1,3-3,6-anhydro-{{Smallcaps|l}}-galactosidase
| ''Bacteroides plebeius''
| neoagarobiose
| His302
| Asp90
| <cite>Hehemann_2_2012</cite>
|-
| [[GH120]]
| none
| parallel β-helix and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}3vsv 3vsv]
| β-xylosidase XylC
| ''Thermoanaerobacterium saccharolyticum'' JW/SL-YS485
| {{Smallcaps|d}}-xylose
| Glu405
| Asp382
| <cite>Huang2012</cite>
|-
| [[GH123]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}5fr0 5fr0]
| exo-β-N-acetyl-galactosaminidase
| ''Clostridium perfringens''
| ''N''-difluoroacetyl-{{Smallcaps|d}}-galactosamine
| Glu345
| internal
| <cite>Noach2016</cite>
|-
| [[GH125]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}5m7y 5m7y]
| exo-α-1,6-mannosidase
| ''Clostridium perfringens''
| 1,6-α-mannotriose
| Asp220
| Glu393
| <cite>Alonso-Gil2016</cite>
|-
| [[GH127]]
| none
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| ''anti''
| [{{PDBlink}}3wrg 3wrg]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bifidobacterium longum''
| {{Smallcaps|l}}-arabinose
| Glu322
| Cys417
| <cite>Huang2014</cite>
|-
| [[GH128]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH1''
|
|
|
|
|
|
|-
| [[GH130]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}5b0s 5b0s]
| β-1,2-mannobiose phosphorylase
| ''Listeria innocua''
| β-1,2-mannotriose
| Asp141-relay
| phosphate
| <cite>Tsuda2015</cite>
|-
| [[GH134]]
| none
| β + α
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}5jug 5jug]
| β-mannanase
| ''Streptomyces sp.''
| mannopentaose
| Glu45
| Asp57
| <cite>Jin2016</cite>
|-
| [[GH137]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|l}}
| unknown
| ''anti''
| [{{PDBlink}}5mui 5mui]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0996
| ''Bacteroides thetaiotaomicron''
| pectin oligosaccharide
| Glu240
| Glu159
| <cite>Ndeh2017</cite>
|
|}

== References ==

<biblio>
# HeightmanVasella1999 Heightman TD and Vasella AT. ''Recent Insights into Inhibition, Structure, and Mechanism of Configuration-Retaining Glycosidases.'' Angew Chem Int Ed. 1999 38(6):750-770. [http://www3.interscience.wiley.com/journal/55000581/abstract Article online].
# Nerinckx2005 pmid=15642336
# Wu2012 pmid=23137336
# Perez1978 Pérez S and Marchessault RH. ''The exo-anomeric effect: experimental evidence from crystal structures.'' Carbohydr res. 1978 65:114-120. [http://dx.doi.org/10.1016/S0008-6215(00)84218-4 DOI:10.1016/S0008-6215(00)84218-4]
# Cramer1997 Cramer CJ, Truhlar DG, and French AD. ''Exo-anomeric effects on energies and geometries of different conformations of glucose and related systems in the gas phase and aqueous solution.'' Carbohydr res. 1997 298:1-14. [http://dx.doi.org/10.1016/S0008-6215(96)00297-2 DOI:10.1016/S0008-6215(96)00297-2]
# Johnson2009 pmid=19733839
# Alonso2016 pmid=26889578
# Gloster2006 pmid=17002288
# van_Bueren2009 pmid=18976664
# Hrmova2001 pmid=11709165
# Varrot2003 pmid=12595701
# Zhou1999 pmid=10508787
# Sulzenbacher1999 pmid=10200171
# Urbanikova2011 pmid=21501386
# Guerin2002 pmid=11884144
# Schubot2004 pmid=14756552
# Suzuki2009 pmid=19279191
# Wan2014 pmid=24419374
# Sandgren2004 pmid=15364577
# Uitdehaag1999 pmid=10331869
# Miyake2003 pmid=12741813
# Harris1993 pmid=8431441
# Allouch2004 pmid=15062085
# Papanikolau2001 pmid=11560481
# Prag2000 pmid=10884356
# Vocadlo2001 pmid=11518970
# Karlsen1996 pmid=15299731
# Baldwin1993 pmid=8259514
# Cartmell2008 pmid=18799462
# Fernandez-Leiro2010 pmid=20592022
# Abbott2007 pmid=17397864
# Sakurama2012 pmid=22451675
# Sim2008 pmid=18036614
# Verhaest2007 pmid=17335500
# Amaya2004 pmid=15130470
# Zhu2012 pmid=23015718
# Maksimainen2011 pmid=21130883
# Merceron2012 pmid=23012371
# Gibson2007 pmid=17455176
# Shah2008 pmid=18599462
# Czjzek2005 pmid=16212978
# Godoy2016 pmid=27685756
# Fujimoto2010 pmid=20739278
# Kitago2007 pmid=17905739
# Davies1996 pmid=15299721
# Lyu2014 pmid=24766439
# Karaveg2005 pmid=15713668
# Nerinckx2008 pmid=18619586
# Pluvinage2013 pmid=23921382
# Hoevel2003 pmid=14517232
# Espina2014 pmid=24816105
# Le_Nours2009 pmid=19089956
# Miyanaga2004 pmid=15292273
# Bianchetti2015 pmid=25752603
# Markovic-Housley2000 pmid=11080624
# Imamura2003 pmid=12618437
# Hill2013 pmid=24297913
# Miyazaki2016 pmid=27688023
# Touhara2014 pmid=24828502
# Suzuki2016 pmid=26494689
# Golan2004 pmid=14573597
# Meng2003 pmid=14517548
# Ito2011 pmid=21354427
# Hurtado-Gerrero2009 pmid=19097997
# Yaoi2007 pmid=17498741
# Thompson2015 pmid=25772148
# Barends2007 pmid=17420245
# Fujimoto2013 pmid=23486481
# Wu2015 pmid=26575439
# Dennis2006 pmid=16565725
# Abbott2009 pmid=19181667
# Hehemann_1_2012 pmid=23150581
# Ficko-Blean2008 pmid=18443291
# Zhu2009 pmid=20081828
# Sogabe2011 pmid=21543843
# Nam2015 pmid=26041776
# Nagae2007 pmid=17459873
# Kitamura2008 pmid=18981178
# Higgins2009 pmid=19608744
# van_Straaten2007 pmid=17502382
# van_Asselt2000 pmid=10684641
# Ndeh2017 pmid=28329766
# Jin2016 Jin Y, Petricevic M, John A, Raich L, Jenkins H, Portela De Souza L, Cuskin F, Gilbert HJ, Rovira C, Goddard-Borger ED, Williams SJ, and Davies GJ. ''A β-Mannanase with a Lysozyme-like Fold and a Novel Molecular Catalytic Mechanism.'' ACS Cent Sci. 2016 Nov [http://dx.doi.org/10.1021/acscentsci.6b00232 DOI:10.1021/acscentsci.6b00232]
# Ohnuma2014 pmid=24582745
# Thompson2012 pmid=22219371
# Xie2016 pmid=27777307
# Williams2014 pmid=24339341
# Hehemann_2_2012 pmid=22393053
# Huang2012 pmid=22992047
# Noach2016 pmid=27038508
# Alonso-Gil2016 pmid=28026180
# Huang2014 Huang CH, Zhu Z, Cheng YS, Chan HC, Ko TP, Chen CC, Wang I, Ho MR, Hsu ST, Zeng YF, Huang YN, Liu JR, Guo RT. ''Structure and Catalytic Mechanism of a Glycoside Hydrolase Family-127 β-L-Arabinofuranosidase (HypBA1).'' J Bioprocess Biotech. 2014 4:171 [http://dx.doi.org/10.4172/2155-9821.1000171 DOI:10.4172/2155-9821.1000171]
# Tsuda2015 pmid=26632508

</biblio>

[[Category:Definitions and explanations]]

Syn/anti lateral protonation

2017-09-18T11:52:52Z

Wim Nerinckx: GH120 is anti

{{CuratorApproved}}
* [[Author]]: ^^^Wim Nerinckx^^^
* [[Responsible Curator]]: ^^^Spencer Williams^^^

----

== Overview ==

This page provides a table that summarizes the spatial positioning of the catalytic [[general acid]] residue in the active sites of [[glycoside hydrolase]]s, relative to the substrate. The table below updates those found in the seminal paper on this concept by Heightman and Vasella <cite>HeightmanVasella1999</cite>, and a following paper by Nerinckx ''et al.'' <cite>Nerinckx2005</cite>.

== Background ==

The ''"not from above, but from the side"'' concept of semi-lateral glycosidic oxygen [[General_acid/base|protonation]] by [[glycoside hydrolase]]s was introduced by Heightman and Vasella <cite>HeightmanVasella1999</cite>. It was originally only described for [[Anomeric centre (alpha and beta)|beta]]-equatorial [[glycoside hydrolase]]s, but appears to be equally applicable to enzymes acting on an [[Anomeric centre (alpha and beta)|alpha]]-axial glycosidic bond <cite>Nerinckx2005</cite>. When dividing [[Sub-site nomenclature|subsite -1]] into half-spaces by a plane defined by the glycosidic oxygen and C1' and H1' of the –1 glycoside, many ligand-complexed structures reveal that the [[General_acid/base|proton donor]] is positioned either in the ''syn'' half-space (near the ring-oxygen of the –1 glycoside), or in the ''anti'' half-space (on the opposite side of the ring-oxygen). Members of the same GH [[Families|family]] appear to share a common ''syn'' or ''anti'' [[General_acid/base|protonator]] arrangement and further, this specificity appears to be preserved within [[Clans|Clans]] of [[Families|families]]. This page's compilation of [[Sub-site nomenclature|subsite -1]] occupied complexes shows that about 70% of all GH [[Families|families]] are ''anti'' [[General_acid/base|protonators]].

Closer inspection of crystal structures of [[Sub-site nomenclature|–1/+1 subsite]]-spanning substrates, or substrate-analogue ligands, in complex with enzymes reveals a further intriguing corollary <cite>Nerinckx2005 Wu2012</cite>. In substrate-bound complexes with ''anti'' [[General_acid/base|protonating]] GH enzymes, the scissile [[Anomeric centre (alpha and beta)|anomeric bond]] (often studied using the thio-analogue) shows a dihedral angle φ (O5'-C1'-[O,S]x-Cx) that is in the lowest-energy synclinal (gauche) conformation. The rationale for this is that a minus synclinal dihedral angle φ for an equatorial glycosidic bond, or plus synclinal for an axial glycosidic bond <cite>Perez1978</cite>, allows for hyperconjugative overlap of the C1'-O5' antibonding orbital with an antiperiplanar-oriented lone pair orbital lobe of the glycosidic oxygen, thereby creating partial double bond character and stabilization of the glycosidic bond by 4–5 kcal/mol; this ground-state stabilizing phenomenon is known as the ‘exo-anomeric effect’ <cite>Cramer1997 Johnson2009 Alonso2016</cite>. ''Anti'' [[General_acid/base|protonation]] occurs on the glycosidic oxygen’s antiperiplanar lone pair, thereby removing the stabilizing exo-anomeric effect. This suggests that ''anti'' [[General_acid/base|protonation]] is an enzymic approach for lowering the activation barrier leading to the [[Transition state|transition state]] (Figure 1 centre).

''Syn'' [[General_acid/base|protonating]] [[glycoside hydrolase]]s apparently make use of a different approach <cite>Nerinckx2005 Wu2012</cite>. In many [[Sub-site nomenclature|–1/+1 subsite]]-spanning ligand complexes, the dihedral angle φ of the scissile anomeric bond has been rotated away from its lowest-energy synclinal position: clockwise to minus-anticlinal or antiperiplanar for beta-equatorial; counterclockwise to plus-anticlinal or antiperiplanar for alpha-axial [[Anomeric centre (alpha and beta)|anomeric bonds]]. This removes the hyperconjugative overlap and thus also the stabilizing exo-anomeric effect. And because of this rotation, a lone pair of the glycosidic oxygen is directed into the ''syn'' half-space, allowing it to be protonated by the ''syn''-positioned [[General_acid/base|proton donor]] (Figure 1 right).

[[File:Syn_anti.jpg|800px|thumb|center|Figure 1. Newman projections, with the glycosidic oxygen as proximal atom and the anomeric carbon as distal atom, showing ''anti'' (centre) versus ''syn'' (right) semi-lateral [[General_acid/base|protonation]] in beta-equatorial (top) and alpha-axial (bottom) [[glycoside hydrolase]]s. The indicated φ is the dihedral angle for O5'-C1'-O4-C4.]]

== Table of ''syn/anti'' protonation examples ==

This table contains only one example per GH [[Families|family]] of a ligand-complexed protein structure where the ''syn'' or ''anti'' positioning of the [[General_acid/base|proton donor]] can be clearly observed; other examples may be available on a [[Families|family-by-family]] basis. The reader is thus advised to consult the [http://www.cazy.org/fam/acc_GH.html#table CAZy database] for a current, comprehensive list of CAZyme structures. Where available, the selected examples are Michaelis-type complexes with the ligand spanning the [[Sub-site nomenclature|-1/+1 subsites]], since these have an intact glycosidic or thioglycosidic bond, or are ''N''-analogs of the substrate (''e.g.'' acarbose). In some examples, the [[General_acid/base|proton donor]] has been mutated (''e.g.'', to the corresponding amide or to an alanine), and in those cases one may wish to look at a superposition of the given PDB example with the structure of the native enzyme. If a Michaelis-type complex is not yet available, the second and third example choices, respectively, are trapped glycosyl-enzyme [[intermediate]]s and product complexes where [[Sub-site nomenclature|subsite -1]] is occupied.

''Please also be aware that this is a large table with many data. Please contact the page Author or Responsible Curator with corrections.''

=== Table ===
This table can be re-sorted by clicking on the icons in the header (''javascript must be turned on in your browser''). To reset the page to be sorted by GH family, click the ''View'' tab at the very top of the page.

{| {{Prettytable}} class="sortable"
|- valign="top"
! '''Family'''
! '''Clan'''
! '''Structure fold '''
! '''Anomeric specificity'''
! '''Mechanism'''
! '''''Syn/anti'' protonator'''
! '''Example PDB ID'''
! '''Enzyme'''
! '''Organism'''
! '''Ligand'''
! '''General acid'''
! '''Nucleophile or General base'''
! '''Reference'''
|-
| [[GH1]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2cer 2cer]
| β-glycosidase S
| ''Sulfolobus solfataricus'' P2
| phenethyl glucoimidazole
| Glu206
| Glu387
| <cite>Gloster2006</cite>
|-
| [[GH2]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| ''anti''
| [{{PDBlink}}2vzu 2vzu]
| exo-β-glucosaminidase
| ''Amicolatopsis orientalis''
| PNP-β-{{Smallcaps|d}}-glucosamine
| Glu469
| Glu541
| <cite>van_Bueren2009</cite>
|-
| [[GH3]]
| none
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| ''anti''
| [{{PDBlink}}1iex 1iex]
| exo-1,3-1,4-glucanase
| ''Hordeum vulgare''
| thiocellobiose
| Glu491
| Asp285
| <cite>Hrmova2001</cite>
|-
| [[GH5]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}1h2j 1h2j]
| endo-β-1,4-glucanase
| ''Bacillus agaradhaerens''
| 2',4'-DNP-2-F-cellobioside
| Glu129
| Glu228
| <cite>Varrot2003</cite>
|-
| [[GH6]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}1qjw 1qjw]
| cellobiohydrolase 2
| ''Hypocrea jecorina''
| (Glc)2-S-(Glc)2
| Asp221
| debated
| <cite>Zhou1999</cite>
|-
| [[GH7]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| ''syn''
| [{{PDBlink}}1ovw 1ovw]
| endo-1,4-glucanase
| ''Fusarium oxysporum''
| thio-(Glc)5
| Glu202
| Glu197
| <cite>Sulzenbacher1999</cite>
|-
| [[GH8]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}1kwf 1kwf]
| endo-1,4-glucanase
| ''Clostridium thermocellum''
| cellopentaose
| Glu95
| Asp278
| <cite>Guerin2002</cite>
|-
| [[GH9]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}1rq5 1rq5]
| cellobiohydrolase
| ''Clostridium thermocellum''
| cellotetraose
| Glu795
| Asp383
| <cite>Schubot2004</cite>
|-
| [[GH10]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2d24 2d24]
| β-1,4-xylanase
| ''Streptomyces olivaceoviridis'' E-86
| xylopentaose
| Glu128
| Glu236
| <cite>Suzuki2009</cite>
|-
| [[GH11]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| ''syn''
| [{{PDBlink}}4hk8 4hk8]
| endo-β-1,4-xylanase
| ''Hypocrea jecorina''
| xylohexaose
| Glu177
| Glu86
| <cite>Wan2014</cite>
|-
| [[GH12]]
| C
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| ''syn''
| [{{PDBlink}}1w2u 1w2u]
| endoglucanase
| ''Humicola grisea''
| thiocellotetraose
| Glu205
| Glu120
| <cite>Sandgren2004</cite>
|-
| [[GH13]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}1cxk 1cxk]
| β-cyclodextrin glucanotransferase
| ''Bacillus circulans''
| maltononaose
| Glu257
| Asp229
| <cite>Uitdehaag1999</cite>
|-
| [[GH14]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}1itc 1itc]
| β-amylase
| ''Bacillus cereus''
| maltopentaose
| Glu172
| Glu367
| <cite>Miyake2003</cite>
|-
| [[GH15]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}1dog 1dog]
| glucoamylase
| ''Aspergillus awamori''
| 1-deoxynojirimycin
| Glu179
| Glu400
| <cite>Harris1993</cite>
|-
| [[GH16]]
| B
| β-jelly roll
| beta-{{Smallcaps|d}}
| retaining
| ''syn''
| [{{PDBlink}}1urx 1urx]
| β-agarase A
| ''Zobellia galactanivorans''
| oligoagarose
| Glu152
| Glu147
| <cite>Allouch2004</cite>
|-
| [[GH17]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH1''
|
|
|
|
|
|
|-
| [[GH18]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}1ffr 1ffr]
| chitinase A
| ''Serratia marcescens''
| (NAG)6
| Glu315
| internal
| <cite>Papanikolau2001</cite>
|-
| [[GH19]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}3wh1 3wh1]
| chitinase
| ''Bryum coronatum''
| (GlcNAc)4
| Glu61
| Glu70
| <cite>Ohnuma2014</cite>
|-
| [[GH20]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}1c7s 1c7s]
| chitobiase
| ''Serratia marcescens''
| chitobiose
| Glu540
| internal
| <cite>Prag2000</cite>
|-
| [[GH22]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| ''syn''
| [{{PDBlink}}1h6m 1h6m]
| lysozyme C
| ''Gallus gallus''
| Chit-2-F-chitosyl
| Glu35
| Asp52
| <cite>Vocadlo2001</cite>
|-
| [[GH23]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}1lsp 1lsp]
| lysozyme G
| ''Cygnus atratus''
| Bulgecin A
| Glu73
| internal
| <cite>Karlsen1996</cite>
|-
| [[GH24]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}148l 148l]
| lysozyme E
| Bacteriophage T4
| chitobiosyl
| Glu11
| Glu26
| <cite>Baldwin1993</cite>
|-
| [[GH26]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2vx6 2vx6]
| exo-β-mannanase
| ''Cellvibrio japonicus'' Ueda107
| Gal1Man4
| Glu221
| Glu338
| <cite>Cartmell2008</cite>
|-
| [[GH27]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}} / beta-{{Smallcaps|l}}
| retaining
| ''anti''
| [{{PDBlink}}3lrm 3lrm]
| α-galactosidase
| ''Saccharomyces cerevisiae''
| raffinose
| Asp209
| Asp141
| <cite>Fernandez-Leiro2010</cite>
|-
| [[GH28]]
| N
| β-helix
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| ''anti''
| [{{PDBlink}}2uvf 2uvf]
| exo-polygalacturonosidase
| ''Yersinia enterocolitica'' ATCC9610D
| digalacturonic acid
| Asp402
| Asp381 Asp403
| <cite>Abbott2007</cite>
|-
| [[GH29]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| retaining
| ''syn''
| [{{PDBlink}}3uet 3uet]
| α-1,3/4-fucosidase
| ''Bifidobacterium longum'' subsp. infantis
| lacto-''N''-fucopentaose II
| Glu217
| Asp172
| <cite>Sakurama2012</cite>
|-
| [[GH30]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2y24 2y24]
| glucurono-xylanase
| ''Dickea chrysanthemi'' D1
| glucuronoxylan tetrasaccharide
| Glu163
| Glu253
| <cite>Urbanikova2011</cite>
|-
| [[GH31]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2qmj 2qmj]
| maltase-glucoamylase
| ''Homo sapiens''
| acarbose
| Asp542
| Asp443
| <cite>Sim2008</cite>
|-
| [[GH32]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2add 2add]
| fructan β-(2,1)-fructosidase
| ''Cichorium intybus''
| sucrose
| Glu201
| Asp22
| <cite>Verhaest2007</cite>
|-
| [[GH33]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}1s0i 1s0i]
| transsialidase
| ''Trypanosoma cruzi''
| sialyllactose
| Asp59
| Tyr342
| <cite>Amaya2004</cite>
|-
| [[GH34]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}4gzw 4gzw]
| N2 neuraminidase
| ''Influenza'' A Tanzania/205/2010 H3N2
| α-{{Smallcaps|d}}-Neup5Ac-(2,3)-β-{{Smallcaps|d}}-Galp-(1,4)-β-{{Smallcaps|d}}-GlcpNAc
| Asp151
| Tyr406
| <cite>Zhu2012</cite>
|-
| [[GH35]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}3ogv 3ogv]
| β-galactosidase
| ''Hypocrea jecorina''
| 2-phenylethyl 1-thio-β-{{Smallcaps|d}}-galactopyranoside
| Glu200
| Glu298
| <cite>Maksimainen2011</cite>
|-
| [[GH36]]
| D
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}4fns 4fns]
| β-galactosidase
| ''Geobacillus stearothermophilus''
| 1-deoxy galactonojirimycin
| Asp584
| Asp478
| <cite>Merceron2012</cite>
|-
| [[GH37]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}2jf4 2jf4]
| trehalase
| ''Escherechia coli''
| validoxylamine
| Asp312
| Glu496
| <cite>Gibson2007</cite>
|-
| [[GH38]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}3czn 3czn]
| Golgi α-mannosidase II
| ''Drosophila melanogaster''
| GlcNAcMan(5)GlcNAc(2)
| Asp341
| Asp204
| <cite>Shah2008</cite>
|-
| [[GH39]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| ''anti''
| [{{PDBlink}}2bfg 2bfg]
| β-xylosidase
| ''Geobacillus stearothermophilus''
| 2,5-dinitrophenyl-β-{{Smallcaps|d}}-xyloside
| Glu160
| Glu278
| <cite>Czjzek2005</cite>
|-
| [[GH42]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| ''anti''
| [{{PDBlink}}4ucf 4ucf]
| β-galactosidase
| ''Bifidobacterium bifidum''
| {{Smallcaps|d}}-galactose
| Glu161
| Glu320
| <cite>Godoy2016</cite>
|-
| [[GH43]]
| F
| 5-fold β-propeller
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| inverting
| ''anti''
| [{{PDBlink}}3akh 3akh]
| exo-1,5-α-{{Smallcaps|l}}-arabinofuranosidase
| ''Streptomyces avermitilis''
| α-1,5-arabinofuranotriose
| Glu196
| Asp220
| <cite>Fujimoto2010</cite>
|-
| [[GH44]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2eqd 2eqd]
| endoglucanase
| ''Clostridium thermocellum''
| cellooctaose
| Glu186
| Glu359
| <cite>Kitago2007</cite>
|-
| [[GH45]]
| none
| 6-stranded β-barrel
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}4eng 4eng]
| endo-1,4-glucanase
| ''Humicola insolens''
| cellohexaose
| Asp121
| Asp10
| <cite>Davies1996</cite>
|-
| [[GH46]]
| I
| lysozyme type
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}4olt 4olt]
| chitosanase
| ''Microbacterium sp.'' OU01
| hexa-glucosamine
| Glu25
| Asp43
| <cite>Lyu2014</cite>
|-
| [[GH47]]
| none
| (α/α)7
| alpha-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}1x9d 1x9d]
| α-mannosidase I
| ''Homo sapiens''
| Me-2-S-(α-Man)-2-thio-α-Man
| Asp463
| Glu599
| <cite>Karaveg2005</cite>, <cite>Nerinckx2008</cite>
|-
| [[GH48]]
| M
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH8''
|
|
|
|
|
|
|-
| [[GH49]]
| N
| β-helix
| alpha-{{Smallcaps|d}}
| inverting
| ''predicted anti by clan''
| ''see at GH28''
|
|
|
|
|
|
|-
| [[GH50]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}4bq5 4bq5]
| exo-β-agarase
| ''Saccharophagus degradans''
| neoagarotetraose
| Glu535
| Glu695
| <cite>Pluvinage2013</cite>
|-
| [[GH51]]
| A
| (β/α)8
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| ''anti''
| [{{PDBlink}}1qw9 1qw9]
| α-{{Smallcaps|l}}-arabinofuranosidase
| ''Geobacillus stearothermophilus''
| PNP-{{Smallcaps|l}}-arabinofuranoside
| Glu175
| Glu294
| <cite>Hoevel2003</cite>
|-
| [[GH52]]
| O
| (α/α)6
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}4c1p 4c1p]
| β-xylosidase
| ''Geobacillus thermoglucosidasius''
| xylobiose
| Asp517
| Glu537
| <cite>Espina2014</cite>
|-
| [[GH53]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2ccr 2ccr]
| β-1,4-galactanase
| ''Bacillus licheniformis''
| galactotriose
| Glu165
| Glu263
| <cite>Le_Nours2009</cite>
|-
| [[GH54]]
| none
| β-sandwich
| beta-{{Smallcaps|d}} / alpha-{{Smallcaps|l}}
| retaining
| ''anti''
| [{{PDBlink}}1wd4 1wd4]
| α-{{Smallcaps|l}}-arabinofuranosidase B
| ''Aspergillus kawachii''
| {{Smallcaps|l}}-arabinofuranose
| Asp297
| Glu221
| <cite>Miyanaga2004</cite>
|-
| [[GH55]]
| none
| β-helix
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}4tz5 4tz5]
| exo-β-1,3-glucanase
| ''Streptomyces sp.'' SirexAA-E
| laminarihexaose
| Glu502
| unknown
| <cite>Bianchetti2015</cite>
|-
| [[GH56]]
| none
| (β/α)7
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}1fcv 1fcv]
| hyaluronidase
| ''Apis mellifera''
| (hyaluron.)4
| Glu113
| internal
| <cite>Markovic-Housley2000</cite>
|-
| [[GH57]]
| none
| (β/α)7
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}1k1y 1k1y]
| glucanotransferase
| ''Thermococcus litoralis''
| acarbose
| Asp214
| Glu123
| <cite>Imamura2003</cite>
|-
| [[GH59]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}4ccc 4ccc]
| β-galactocerebrosidase
| ''Mus musculus''
| PNP-β-{{Smallcaps|d}}-galactoside
| Glu182
| Glu258
| <cite>Hill2013</cite>
|-
| [[GH62]]
| F
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| unknown
| ''predicted anti by clan''
| ''see at GH43''
|
|
|
|
|
|
|-
| [[GH63]]
| G
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}5ca3 5ca3]
| α-glucosidase
| ''Escherechia coli''
| glucose and lactose
| Asp501
| Glu727
| <cite>Miyazaki2016</cite>
|-
| [[GH65]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}} (and α-{{Smallcaps|l}}-rham)
| inverting
| ''anti''
| [{{PDBlink}}4ktr 4ktr]
| 2-O-α-glucosylglycerol phosphorylase
| ''Bacillus selenitireducens''
| isofagomine
| Glu475
| phosphate
| <cite>Touhara2014</cite>
|-
| [[GH66]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}5axh 5axh]
| dextranase
| ''Thermoanaerobacter pseudethanolicus''
| isomaltohexaose
| Glu374
| Asp312
| <cite>Suzuki2016</cite>
|-
| [[GH67]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}1l8n 1l8n]
| α-glucuronidase
| ''Geobacillus stearothermophilus''
| 4-O-methyl-{{Smallcaps|d}}-glucuronic acid and xylotriose
| Glu286
| Asp364 Glu392
| <cite>Golan2004</cite>
|-
| [[GH68]]
| J
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}1pt2 1pt2]
| levansucrase
| ''Bacillus subtilis''
| sucrose
| Glu342
| Asp86
| <cite>Meng2003</cite>
|-
| [[GH70]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}3aic 3aic]
| glucansucrase
| ''Streptococcus mutans''
| α-acarbose
| Glu515
| Asp477
| <cite>Ito2011</cite>
|-
| [[GH72]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2w62 2w62]
| β-1,3-glucanotransferase
| ''Saccharomyces cerevisiae'' S288C
| laminaripentaose
| Glu176
| Glu275
| <cite>Hurtado-Gerrero2009</cite>
|-
| [[GH74]]
| none
| 7-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}2ebs 2ebs]
| cellobiohydrolase (OXG-RCBH)
| ''Geotrichum sp.'' m128
| xyloglucan heptasaccharide
| Asp465
| Asp35
| <cite>Yaoi2007</cite>
|-
| [[GH76]]
| none
| (α/α)6
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}5agd 5agd]
| endo-α-1,6-mannanase
| ''Bacillus circulans''
| α-1,6-mannopentaose
| Asp125
| Asp124
| <cite>Thompson2015</cite>
|-
| [[GH77]]
| H
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}1esw 1esw]
| amylomaltase
| ''Thermus aquaticus''
| acarbose
| Asp395
| Asp293
| <cite>Przylas2000</cite>
|-
| [[GH78]]
| H
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| ''anti''
| [{{PDBlink}}3w5n 3w5n]
| α-{{Smallcaps|l}}-rhamnosidase
| ''Streptomyces avermitilis''
| {{Smallcaps|l}}-rhamnose
| Glu636
| Glu895
| <cite>Fujimoto2013</cite>
|-
| [[GH79]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}5e9c 5e9c]
| heparanase
| ''Homo sapiens''
| heparin tetrasaccharide
| Glu225
| Glu343
| <cite>Wu2015</cite>
|-
| [[GH80]]
| I
| α + β
| beta-{{Smallcaps|d}}
| inverting
| ''predicted syn by clan''
| ''see at GH24''
|
|
|
|
|
|
|-
| [[GH83]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH33''
|
|
|
|
|
|
|-
| [[GH84]]
| none
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2chn 2chn]
| β-''N''-acetyl-glucosaminidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| NAG-thiazoline
| Glu242
| internal
| <cite>Dennis2006</cite>
|-
| [[GH85]]
| K
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2w92 2w92]
| endo-β-''N''-acetyl-glucosaminidase D
| ''Streptococcus pneumoniae'' TIGR4
| NAG-thiazoline
| Glu337
| internal
| <cite>Abbott2009</cite>
|-
| [[GH86]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}4aw7 4aw7]
| β-porphyranase
| ''Bacteroides plebeius''
| porphyran fragment
| Glu152
| Glu279
| <cite>Hehemann_1_2012</cite>
|-
| [[GH89]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}2vcb 2vcb]
| α-''N''-acetyl-glucosaminidase
| ''Clostridium perfringens''
| PUGNAc
| Glu483
| Glu601
| <cite>Ficko-Blean2008</cite>
|-
| [[GH92]]
| none
| (α/α)6 and β-sandw.
| alpha-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}2ww1 2ww1]
| α-1,2-mannosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| thiomannobioside
| Glu533
| Asp644 Asp642
| <cite>Zhu2009</cite>
|-
| [[GH93]]
| E
| 6-fold β-propeller
| alpha-{{Smallcaps|l}}
| retaining
| ''anti''
| [{{PDBlink}}3a72 3a72]
| exo-arabinanase
| ''Penicillium chrysogenum''
| arabinobiose
| Glu246
| Glu174
| <cite>Sogabe2011</cite>
|-
| [[GH94]]
| none
| (α/α)6
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}4zli 4zli]
| cellobionic acid phosphorylase
| ''Saccharophagus degradans''
| 3-O-β-{{Smallcaps|d}}-glucopyranosyl-α-{{Smallcaps|d}}-glucopyranuronic acid
| Asp472
| phosphate
| <cite>Nam2015</cite>
|-
| [[GH95]]
| none
| (α/α)6
| alpha-{{Smallcaps|l}}
| inverting
| ''anti''
| [{{PDBlink}}2ead 2ead]
| α-1,2-{{Smallcaps|l}}-fucosidase
| ''Bifidobacterium bifidum''
| Fuc-α-1,2-Gal
| Glu566
| Asn423 Asp766
| <cite>Nagae2007</cite>
|-
| [[GH97]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining + inverting
| ''anti''
| [{{PDBlink}}2zq0 2zq0]
| α-glucosidase
| ''Bacteroides thetaiotaomicron'' VPI-5482
| acarbose
| Glu532
| Glu508
| <cite>Kitamura2008</cite>
|-
| [[GH98]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}2wmg 2wmg]
| endo-β-1,4-galactosidase
| ''Streptococcus pneumoniae''
| A-LewisY pentasaccharide
| Glu158
| Asp251 Glu301
| <cite>Higgins2009</cite>
|-
| [[GH99]]
| none
| (β/α)8
| alpha-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}4ad4 4ad4]
| endo-α-mannosidase
| ''Bacteroides xylanisolvens''
| glucose-1,3-isofagomine and α-1,2- mannobiose
| Glu336
| debated
| <cite>Thompson2012</cite>
|-
| [[GH100]]
| none
| (α/α)6 core
| beta-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}5gop 5gop]
| invertase
| ''Anabaena (Nostoc) sp.'' pcc7120
| sucrose
| Asp188
| Glu414
| <cite>Xie2016</cite>
|-
| [[GH102]]
| none
| double-ψ β-barrel
| beta-{{Smallcaps|d}}
| retaining
| ''syn''
| [{{PDBlink}}2pi8 2pi8]
| lytic transglycosylase A
| ''Escherichia coli''
| chitohexaose
| Asp308
| none
| <cite>van_Straaten2007</cite>
|-
| [[GH103]]
| none
| lysozyme type
| beta-{{Smallcaps|d}}
| retaining
| ''syn''
| [{{PDBlink}}1d0k 1d0k]
| lytic transglycosylase SLT35
| ''Escherichia coli''
| murodipeptides
| Glu162
| internal
| <cite>van_Asselt2000</cite>
|-
| [[GH106]]
| none
| (β/α)8
| alpha-{{Smallcaps|l}}
| inverting
| ''anti''
| [{{PDBlink}}5mwk 5mwk]
| α-{{Smallcaps|l}}-rhamnosidase BT_0986
| ''Bacteroides thetaiotaomicron''
| pectin heptasaccharide
| Glu461
| Glu593 or Glu561
| <cite>Ndeh2017</cite>
|-
| [[GH113]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}4cd8 4cd8]
| β-mannanase
| ''Alicyclobacillus acidocaldarius''
| mannobioimidazole
| Glu151
| Glu231
| <cite>Williams2014</cite>
|-
| [[GH116]]
| O
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see at GH52''
|
|
|
|
|
|
|-
| [[GH117]]
| none
| 5-fold β-propeller
| alpha-{{Smallcaps|l}}
| inverting
| ''anti''
| [{{PDBlink}}4ak7 4ak7]
| α-1,3-3,6-anhydro-{{Smallcaps|l}}-galactosidase
| ''Bacteroides plebeius''
| neoagarobiose
| His302
| Asp90
| <cite>Hehemann_2_2012</cite>
|-
| [[GH120]]
| none
| parallel β-helix and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}3vsv 3vsv]
| β-xylosidase XylC
| ''Thermoanaerobacterium saccharolyticum'' JW/SL-YS485
| {{Smallcaps|d}}-xylose
| Glu405
| Asp382
| <cite>Huang2012</cite>
|-
| [[GH123]]
| none
| (β/α)8 and β-sandwich
| beta-{{Smallcaps|d}}
| retaining
| ''anti''
| [{{PDBlink}}5fr0 5fr0]
| exo-β-N-acetyl-galactosaminidase
| ''Clostridium perfringens''
| ''N''-difluoroacetyl-{{Smallcaps|d}}-galactosamine
| Glu345
| internal
| <cite>Noach2016</cite>
|-
| [[GH125]]
| L
| (α/α)6
| alpha-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}5m7y 5m7y]
| exo-α-1,6-mannosidase
| ''Clostridium perfringens''
| 1,6-α-mannotriose
| Asp220
| Glu393
| <cite>Alonso-Gil2016</cite>
|-
| [[GH127]]
| none
| (α/α)6 and β-sandwich
| beta-{{Smallcaps|l}}
| retaining
| ''anti''
| [{{PDBlink}}3wrg 3wrg]
| β-{{Smallcaps|l}}-arabinofuranosidase
| ''Bifidobacterium longum''
| {{Smallcaps|l}}-arabinose
| Glu322
| Cys417
| <cite>Huang2014</cite>
|-
| [[GH128]]
| A
| (β/α)8
| beta-{{Smallcaps|d}}
| retaining
| ''predicted anti by clan''
| ''see e.g. at GH1''
|
|
|
|
|
|
|-
| [[GH130]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|d}}
| inverting
| ''anti''
| [{{PDBlink}}5b0s 5b0s]
| β-1,2-mannobiose phosphorylase
| ''Listeria innocua''
| β-1,2-mannotriose
| Asp141-relay
| phosphate
| <cite>Tsuda2015</cite>
|-
| [[GH134]]
| none
| β + α
| beta-{{Smallcaps|d}}
| inverting
| ''syn''
| [{{PDBlink}}5jug 5jug]
| β-mannanase
| ''Streptomyces sp.''
| mannopentaose
| Glu45
| Asp57
| <cite>Jin2016</cite>
|-
| [[GH137]]
| none
| 5-fold β-propeller
| beta-{{Smallcaps|l}}
| unknown
| ''anti''
| [{{PDBlink}}5mui 5mui]
| β-{{Smallcaps|l}}-arabinofuranosidase BT_0996
| ''Bacteroides thetaiotaomicron''
| pectin oligosaccharide
| Glu240
| Glu159
| <cite>Ndeh2017</cite>
|
|}

== References ==

<biblio>
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# Nerinckx2005 pmid=15642336
# Wu2012 pmid=23137336
# Perez1978 Pérez S and Marchessault RH. ''The exo-anomeric effect: experimental evidence from crystal structures.'' Carbohydr res. 1978 65:114-120. [http://dx.doi.org/10.1016/S0008-6215(00)84218-4 DOI:10.1016/S0008-6215(00)84218-4]
# Cramer1997 Cramer CJ, Truhlar DG, and French AD. ''Exo-anomeric effects on energies and geometries of different conformations of glucose and related systems in the gas phase and aqueous solution.'' Carbohydr res. 1997 298:1-14. [http://dx.doi.org/10.1016/S0008-6215(96)00297-2 DOI:10.1016/S0008-6215(96)00297-2]
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# Meng2003 pmid=14517548
# Ito2011 pmid=21354427
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# Thompson2015 pmid=25772148
# Przylas2000 pmid=11082203
# Fujimoto2013 pmid=23486481
# Wu2015 pmid=26575439
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# Abbott2009 pmid=19181667
# Hehemann_1_2012 pmid=23150581
# Ficko-Blean2008 pmid=18443291
# Zhu2009 pmid=20081828
# Sogabe2011 pmid=21543843
# Nam2015 pmid=26041776
# Nagae2007 pmid=17459873
# Kitamura2008 pmid=18981178
# Higgins2009 pmid=19608744
# van_Straaten2007 pmid=17502382
# van_Asselt2000 pmid=10684641
# Ndeh2017 pmid=28329766
# Jin2016 Jin Y, Petricevic M, John A, Raich L, Jenkins H, Portela De Souza L, Cuskin F, Gilbert HJ, Rovira C, Goddard-Borger ED, Williams SJ, and Davies GJ. ''A β-Mannanase with a Lysozyme-like Fold and a Novel Molecular Catalytic Mechanism.'' ACS Cent Sci. 2016 Nov [http://dx.doi.org/10.1021/acscentsci.6b00232 DOI:10.1021/acscentsci.6b00232]
# Ohnuma2014 pmid=24582745
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# Noach2016 pmid=27038508
# Alonso-Gil2016 pmid=28026180
# Huang2014 Huang CH, Zhu Z, Cheng YS, Chan HC, Ko TP, Chen CC, Wang I, Ho MR, Hsu ST, Zeng YF, Huang YN, Liu JR, Guo RT. ''Structure and Catalytic Mechanism of a Glycoside Hydrolase Family-127 β-L-Arabinofuranosidase (HypBA1).'' J Bioprocess Biotech. 2014 4:171 [http://dx.doi.org/10.4172/2155-9821.1000171 DOI:10.4172/2155-9821.1000171]
# Tsuda2015 pmid=26632508

</biblio>

[[Category:Definitions and explanations]]