CAZypedia - User contributions [en-ca]

Glycoside Hydrolase Family 16

2019-09-25T15:43:20Z

Mirjam Czjzek:

{{CuratorApproved}}
* [[Author]]: [[User:JensEklof|Jens Eklöf]] and ^^^Jan-Hendrik Hehemann^^^
* [[Responsible Curator]]: ^^^Harry Brumer^^^
----

<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family 16'''
|-
|'''Clan'''
|GH-B
|-
|'''Mechanism'''
|retaining
|-
|'''Active site residues'''
|known
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}GH16.html
|}
</div>

== Substrate specificities ==
The members of family 16 are active on β-1,4 or β-1,3 glycosidic bonds in various glucans and galactans. A wide diversity of [[glycoside hydrolases]] active on plant and marine polysaccharides are found in GH16, including:
* keratan-sulfate ''[[endo]]''-1,4-β-galactosidases (EC [{{EClink}}3.2.1.103 3.2.1.103]),
* ''[[endo]]''-1,3-β-galactanases (EC [{{EClink}}3.2.1.* 3.2.1.-]),
* ''[[endo]]''-1,3-β-glucanases (EC [{{EClink}}3.2.1.39 3.2.1.39]),
* ''[[endo]]''-1,3(4)-β-glucanases (EC [{{EClink}}3.2.1.6 3.2.1.6]),
* licheninases (EC [{{EClink}}3.2.1.73 3.2.1.73]),
* β-agarases (EC [{{EClink}}3.2.1.81 3.2.1.81]),
* β-porphyranases (EC [{{EClink}}3.2.1.178 3.2.1.178]) <cite>Hehemann2010</cite>,
* κ-carrageenases (EC [{{EClink}}3.2.1.83 3.2.1.83]), and
* endo-xyloglucanases (EC [{{EClink}}3.2.1.151 3.2.1.151], a.k.a. xyloglucan endo-hydrolases, XEHs, in plants <cite>Eklof2010</cite>).

Notably, some members of GH16 are predominant [[transglycosylases]]. These include the plant xyloglucan:xyloglucosyltransferases (EC [{{EClink}}2.4.1.207 2.4.1.207], a.k.a. xyloglucan endo-transglycosylases, XETs) <cite>Eklof2010</cite> and yeast chitin/beta-glucan crosslinking enzymes Crh1 and Crh2 <cite>Cabib2008 Mazan2013 Blanco2015</cite>. Some invertebrate GH16 proteins have lost their catalytic amino acids and are involved in immune response activation through the Toll pathway upon binding of β-1,3 glucan. The role of the GH16 domain in this immune response has not been fully elucidated <cite>Lee2009</cite>.

Several of the activities observed for GH16 members are delineated into individual sequence-based subfamilies, while other polyspecific subfamilies capture a range of activities <cite>Viborg2019</cite>.

<gallery widths=270px perrow=3 caption="Diverse polysaccharides cleaved by GH16 enzymes">

File:AgarIII.png|'''Agar''' <br> β-D-Gal''p''-(1,4)-α-L-3,6-anhydro-Gal''p''-1,3-β-D-Gal''p''-(1,4)-α-L-3,6-anhydro-Gal''p''

File:Kappa_carrageenan.png|'''κ-carrageenan''' <br> β-D-Gal''p''-(1,4)-α-D-3,6-anhydro-Gal''p''-1,3-β-D-Gal''p''-(1,4)-α-D-3,6-anhydro-Gal''p''

File:porphyran.png|'''Porphyran''' <br>

File:laminaritetraose.png|'''β-1,3-glucan''' <br> β-D-Glc''p''-(1,3)- β-D-Glc''p''-(1,3)- β-D-Glc''p''-(1,3)- β-D-Glc''p''

File:keratan_sulphate.png|'''Keratan sulphate''' <br> β-D-Gal''p''-(1,4)- β-D-Glc''p''NAc 6-sulphate-(1,3)- β-D-Gal''p''-(1,4)- β-D-Glc''p''NAc 6-sulphate

File:beta_13_galactan.png|'''β-1,3-galactan''' <br> β-D-Gal''p''-(1,3)- β-D-Gal''p''-(1,3)- β-D-Gal''p''-(1,3)- β-D-Gal''p''

File:MLG_pentaose.png|'''β-1,4/1,3-glucan''' <br> β-D-Glc''p''-(1,4)- β-D-Glc''p''-(1,4)- β-D-Glc''p''-(1,3)- β-D-Glc''p''-(1,4)- β-D-Glc''p''

File:beta_14_galactan.png|'''β-1,4-galactan''' <br> β-D-Gal''p''-(1,4)- β-D-Gal''p''-(1,4)- β-D-Gal''p''-(1,4)- β-D-Gal''p''

File:Xyloglucan.png|'''Xyloglucan''' <br>

</gallery>

== Kinetics and Mechanism ==
Members of GH16 enzymes are [[retaining]] enzymes, as first shown by NMR <cite>Malet1993</cite> on an ''[[endo]]''-1,3-1,4-β-D-glucan 4-glucanohydrolase from ''Bacillus licheniformis''. As such, they utilize a covalent glycosyl-enzyme intermediate, which is broken-down by glycosyl transfer <cite>Sinnott1990 Bissaro2015</cite> to water or a carbohydrate acceptor substrate in [[glycoside hydrolases]] or [[transglycosylases]], respectively.

== Catalytic Residues ==
The [[catalytic nucleophile]] of GH16 enzymes was first proposed using a non-specific epoxyalkyl β-glycoside inhibitor and identification of the site of covalent labelling using ESI-MS and Edman degradation on an ''[[endo]]''-1,3-1,4-β-D-glucan 4-glucanohydrolase from ''Bacillus amyloliquefaciens'' <cite>Hoj1992</cite>. This was subsequently verified by azide rescue of the E134A mutant of a ''Bacillus licheniformis'' 1,3-1,4-β-D-glucan 4-glucanohydrolase resulting in an α-glycosyl azide from the β-glycoside substrate <cite>Viladot1998</cite>. The [[general acid/base]] residue was identified by making the E138A site-directed mutant of the ''Bacillus licheniformis'' 1,3-1,4-β-D-glucan 4-glucanohydrolase together with kinetic analysis and azide rescue, which resulted in a β-glycosyl azide product <cite>Viladot1998</cite>. These structurally conserved catalytic residues have been confirmed in a number of other GH16 members, including plant XETs and XEHs <cite>Gullfot2009 Piens2007</cite>, and yeast Crh1 and Crh2 <cite>Blanco2015</cite>.

The mechanistic analysis of bacterial mixed-linkage [[endo]]-glucanases has been expertly reviewed in the broader context of GH16 <cite>Planas2000</cite>.

== Three-dimensional structures ==
Proteins in GH16 share a β-jelly-roll fold in which two β-sheets align in a curved, sandwich-like manner and present a cleft-shaped active-site bounded by loops extending from the β-strands. The first solved 3D structure was a hybrid protein of licheninase M from ''Paenibacillus macerans'' and BglA from ''Bacillus amyloliquefaciens'' ([{{PDBlink}}1byh PDB 1byh]) in 1992 <cite>Keitel1993</cite>. Many three-dimensional structures have been solved of family 16 members of archeal, bacterial, and eukaryotic origin (see http://www.cazy.org/GH16_structure.html for an updated list). Of these, the first eukaryotic 3D structure was the xyloglucan ''endo''-transglycosylase ''Ptt''XET16-34 from ''Populus tremula×tremuloides'' ([{{PDBlink}}1umz PDB 1umz]) <cite>Johansson2004</cite> and the first archeal 3D structure was a ''[[endo]]''-1,3-β-glucanase Lam16 from ''Pyrococcus furiosus'' ([{{PDBlink}}2vy0 PDB 2vy0]) <cite>Ilari2009</cite>.

The structural diversity of GH16 members across sequence-related subfamilies has been reviewed in detail <cite>Viborg2019</cite>.
== Evolution of GH16 ==
[[Image:TreeGH16new.png|thumb|right|450px|'''Figure 1. Proposed evolution of GH16 (''click to enlarge'').''']]
GH16 is a member of [[clans|clan]] GH-B together with [[GH7]]; both families share the β-jellyroll fold. The different specificities of GH16 are proposed to have evolved from an ancestral β-1,3-glucanase <cite>Barbeyron1998</cite>. This proposal was first elaborated using a structure-based phylogeny approach, which suggested that an early branching event lead to the evolution of the bacterial κ-carrageenases and the β-agarases, while a later branching event lead to the bacterial licheninases and the plant XETs <cite>Michel2001</cite> (Figure 1). GH16 has more recently been divided into subfamilies within CAZy, the corresponding phylogenetic analysis of which supports this overall evolutionary trajectory <cite>Viborg2019</cite>.

Particularly notable, the GH16 active-site residues are located in-train on one beta-strand at the center of the substrate binding cleft. Depending upon the phylogenetic clade, this beta-strand features one of two topologies. The beta-bulge motif, which has the consensus sequence EXDXXE, is more frequent in GH16 compared to the regular beta-strand with the consensus sequence EXDXE (the [[catalytic nucleophile]] is the first glutamate and the [[catalytic acid/base]] is the second, with a proposed "helper" asparate in-between <cite>Planas2000</cite>). Due to the predominance of the beta-bulge motif and its presence as the only motif in [[GH7]], Michel et al. proposed that the beta-bulge is the ancestral motif, which subsequently gave rise to the regular beta-strand of extant plant XETs and bacterial licheninases <cite>Michel2001</cite>.

Within plant lineages, similar structure-based phylogenetic approaches have suggested that XEHs evolved subsequently to XEHs within the ''xyloglucan endo-transglycosylase/hydrolase (XTH)'' gene family <cite>Baumann2007 Eklof2010</cite>. The identification of a group of bifunctional GH16 [[glycoside hydrolases]], which is active on both mixed-linkage beta-glucan and xyloglucan, provides additional support for the close evolutionary relationship of XETs and licheninases <cite>Eklof2013 McGregor2016 Behar2018</cite>.

== Family firsts ==
; First stereochemistry determination : ''Bacillus licheniformis'' 1,3-1,4-β-D-glucan 4-glucanohydrolase by NMR <cite>Malet1993</cite>.
; First [[catalytic nucleophile]] identification : Suggested in ''Bacillus amyloliquefaciens'' 1,3-1,4-β-D-glucan 4-glucanohydrolase via non-specific epoxyalkyl β-glycoside labeling <cite>Hoj1992</cite>. Later verified by azide rescue of inactivated mutants <cite>Viladot1998</cite>.
; First [[general acid/base]] residue identification : ''Bacillus licheniformis'' 1,3-1,4-β-D-glucan 4-glucanohydrolase, first suggested by sequence homology and mutational studies <cite>Juncosa1994</cite>. This was later verified by azide rescue of inactivated mutants <cite>Viladot1998</cite>.
; First 3-D structure : A hybrid licheninase (''Bacillus amyloliquefaciens'' and ''Paenibacillus macerans'') by X-ray crystallography ([{{PDBlink}}1byh PDB 1byh]) <cite>Keitel1993</cite>.

== Reference list ==
<biblio>
#Johansson2004 pmid=15020748
#Hoj1992 pmid=1360982
#Malet1993 pmid=8280073
#Keitel1993 pmid=8099449
#Juncosa1994 pmid=8182059
#Viladot1998 pmid=9698381
#Ilari2009 pmid=19154353
#Michel2001 pmid=11435116 tree GH16
#Barbeyron1998 pmid=9580981 first GH16 paper
#Baumann2007 pmid=17557806
#Planas2000 pmid=11150614
#Hehemann2010 pmid=20376150
#Kotake2011 pmid=21653698
#Lee2009 pmid=19712587
#Eklof2010 pmid=20421457
#Sinnott1990 Sinnott, M.L. (1990) Catalytic mechanisms of enzymic glycosyl transfer. Chem. Rev. 90, 1171-1202. [http://dx.doi.org/10.1021/cr00105a006 DOI: 10.1021/cr00105a006]
#Cabib2008 pmid=18694928
#Mazan2013 pmid=23919454
#Blanco2015 pmid=25495733
#Gullfot2009 pmid=19419143
#Piens2007 pmid=18043802
#Eklof2013 pmid=23572521
#Bissaro2015 pmid=25793417
#McGregor2016 pmid=27859885

#Viborg2019 pmid=31501245
#Behar2018 pmid=29932263</biblio>

[[Category:Glycoside Hydrolase Families|GH016]]

Carbohydrate Binding Module Family 6

2014-01-07T07:53:56Z

Mirjam Czjzek:

{{CuratorApproved}}
* [[Author]]: ^^^Mirjam Czjzek^^^
* [[Responsible Curator]]: ^^^Mirjam Czjzek^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}CBM6.html
|}
</div>


== Ligand specificities ==
The ligand specificity of the first characterized CBM6, originating from a multimodular xylanase from ''Clostridium thermocellum'', was determined to be xylan <cite>Fernandes1999</cite>, although the results showed that this CBM6 was also able to bind to avicel and acid-swollen cellulose. This was also the first CBM6 for which a 3D structure was determined <cite>Czjzek2001</cite>, and multiple sequence alignments, analyzed in the light of the first 3D structure, already gave clear indications that large diversity in specificity was to be expected among CBM6 modules <cite>Czjzek2001</cite>. The first ligand-bound complex of a xylanase CBM6 (CsCBM6-3) from ''Clostridium stercorarium'' was crystallized by Boraston et al. <cite>Boraston2003</cite>. Remarkably, the characterization and 3D structure of a CBM6 from ''Cellvibrio mixtus'' revealed two distinct binding sites that displayed differential binding specificities <cite>Henshaw2004;Pires2004</cite>. CBM6 modules are in general attached to bacterial or archeal polysaccharide degrading enzymes and can be found attached to xylanases, cellulases, agarases, laminarinases, etc <cite>Michel2009</cite>. Interestingly, modules assigned to the CBM6 family have also been found associated to fungal enzymes and to the α-subunit of the coagulation factor G in horseshoe crabs [http://www.cazy.org/CBM6_eukaryota.html (see the eukarotic CBM6 occurence]). In the latter case, the β-1,3-glucan binding of the C-terminal tandem CBM6s has been demonstrated <cite>Takaki2002</cite>. Those CBM6s having characterized binding specificities cover : both linear and branched/decorated xylan, β-1,4-glucan (or cellulose), mixed-linked β-1,3-1,4-glucan (or lichenan), agarose, β-1,3-glucan (or laminarin) and chitin. Based on phylogenetic analyses of all reported CBM6 sequences in 2009 (a total of 167), four subfamilies have been defined that coincide with classes of substrate binding specificity as follows : subfamily 6a, hemicellulose; subfamily 6b, xylan; subfamily 6c, β-glucans with a variety of linkages; and subfamily 6d, agarose <cite>Abbott2009</cite>.

== Structural Features ==
Likewise many other CBMs the CBM6 modules, roughly containing 120 amino acids, display the overall fold of a β-sandwich, predominantly consisting of five antiparallel β-strands on one face and four antiparallel β-strands on the other face, connected by loops with variable lengths. Within the hierarchal CATH classification the modules belong to the jelly-roll superfamily [http://www.cathdb.info/version/3.5/superfamily/2.60.120.260 2.60.120.260] called "galactose-binding domain-like" that contains 515 unique domains.
The first identified ligand binding site was not, as usual, located at a shallow cleft on the concave surface of the β-sheets (binding site II, formerly called cleft B in CBM6). Alternatively, a binding site was found located at the apex, within the connecting loops of the two β-sheets (binding site I, formerly cleft A in CBM6) ([{{PDBlink}}1gmm PDB 1gmm]). Due to the existance of the dual binding sites in CBM6s, both Type B and C binding properties have been observed for individual CBM6s. Interestingly, some CBM6s display binding affinities for both binding sites ([{{PDBlink}}1uyy PDB 1uyy]), either with distinct specificities for each site ([{{PDBlink}}1uy0 PDB 1uy0] and [{{PDBlink}}1uyz PDB 1uyz]) or synergistic binding involving both sites at the same time <cite>Pires2004</cite>, while binding properties of other CBM6s make use of only one binding site, which is in general site I at the apex (i.e. [{{PDBlink}}1uxx PDB 1uxx];[{{PDBlink}}1nae PDB 1nae];[{{PDBlink}}1w9w PDB 1w9w]). The apex site I is made up of two important, highly conserved aromatic residues (mostly W and Y) that "sandwich" a sugar monomer <cite>Czjzek2001;Abbott2009</cite>. These conserved residues are neighboured by a much more variable loop (defined as zone E in Abbott et al. <cite>Abbott2009</cite>) that make up the diversity in binding specificity. Consistantly, a variable number of sugar-binding subites have been observed for site I, ranging from one (end binder) up to five binding subsites. The precise structural and energetic contributions of four of the binding subsites have been dissected, for the first time, in detail by combining crystallography and ITC in the case of the ''Clostridium stercorarium ''CsCBM6-1 <cite>Lammerts2004</cite>. To date, only one CBM6 has been structurally and biochemically characterized that makes use of binding site II, which is the CBM6 from ''Cellvibrio mixtus'' <cite>Henshaw2004;Pires2004</cite> ([{{PDBlink}}1uxz PDB 1uxz]). An updated list of all available three-dimensional structures is accessible at the [http://www.cazy.org/CBM6_structure.html Cazy CBM6 structures page].

== Functionalities ==
The predominant functional role to date described for CBM6 modules is carbohydrate binding and targeting. It has been shown that this type of module synergistically enhances the activity of the adjacent catalytic domain on insoluble substrates.
The most common associated modules are enzymes such as xylanases, lichenases, β-agarases, laminarinases, deacetylases; other modules that have been found associated to CBM6 are dockerins and in eukaryotic organisms coagulation factors.
The CBM6 from ''Clostridium thermocellum'' has been used to label plant tissues <cite>McCartney2004</cite>.

== Family Firsts ==
;First Identified
:The xylose binding CBM6 from a multi-modular xylanase/actetyl-esterase from ''Clostridium thermocellum'' (CtCBM6) was the first to be identified and biochemically characterized. To a lesser extent the module was also able to bind to avicel and acid-swollen cellulose <cite>Fernandes1999</cite>.
;First Structural Characterization
:The same xylose binding CBM6 from ''Clostridium thermocellum'' ([{{PDBlink}}1gmm PDB 1gmm]) was also the first structurally characterized CBM6. The 3D structure revealed that the location of the ligand-binding site of carbohydrate-binding modules that have evolved from a common sequence was not conserved <cite>Czjzek2001</cite>. The first CBM6 in complex with its ligand was determined for the CsCBM6-3 from ''Clostridium stercorarium'' ([{{PDBlink}}1o8p PDB 1o8p])<cite>Boraston2003</cite>.
== References ==
<biblio>
#Fernandes1999 pmid=10432306
#Czjzek2001 pmid=11673472
#Boraston2003 pmid=12634060
#Henshaw2004 pmid=15004011
#Pires2004 pmid=15010454
#Michel2009 pmid=19240276
#Takaki2002 pmid=11830593
#Abbott2009 pmid=19788273
#Lammerts2004 pmid=15223327
#McCartney2004 pmid=14769335

</biblio>

[[Category:Carbohydrate Binding Module Families|CBM006]]

Glycoside Hydrolase Family 86

2014-01-06T08:27:02Z

Mirjam Czjzek: /* Substrate specificities */

{{CuratorApproved}}
* [[Author]]: ^^^Mirjam Czjzek^^^
* [[Responsible Curator]]: ^^^Mirjam Czjzek^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH86'''
|-
|'''Clan'''
|GH-A
|-
|'''Mechanism'''
|probably retaining
|-
|'''Active site residues'''
|inferred from clan GH-A as two Glu
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}GH86.html
|}
</div>


== Substrate specificities ==
[[Glycoside hydrolases]] of family 86 have first been identified to be β-agarases (EC [{{EClink}}3.2.1.81 3.2.1.81]) that cleave β-1,4 glycosidic bonds of agarose. This polysaccharide chain is ideally made of alternating 1,3-linked β-D-galactose (G) and 1,4-linked 3,6-anhydro-α-L-galactose (LA) residues forming a parallel double helix. Four agarolytic enzymes have been characterized: AgrA from ''Pseudoalteromonas atlantica'', AgaO from ''Microbulbifer thermotolerans JAMB-A94'', Aga86E from ''Saccharophagus degradans 2-40'' <cite>Belas1989,Ohta2004,Ekborg2006</cite> and more recently a GH86 β-agarase from a non marine ''Vibrio'' species (sp. OA-2007)<cite>Ariga2012</cite>. AgaO from ''M. thermotolerans'' was reported to be an endo-hydrolytic enzyme, releasing neoagaro-hexaose as main product <cite>Ohta2004</cite>, while the recombinant Aga86E from ''S. degradans'' released only neoagarobiose in an exo-acting manner <cite>Ekborg2006</cite>. In june 2012, a first GH86 enzyme was identified in the human gut Bacteroidetes ''B. plebeius'' that was active on porphyran, an agarocolloïd in which the 3,6-anhydro-L-galactose unit (LA) of neutral agarose is replaced by L-galactose-6-sulfate (L6S). The endo-acting enzyme, BpGH86A, is inactive on agarose and the main products released by cleavage of β-1,4 glycosidic bonds of porphyran, are tetrasaccharides having the sequence L6S-G-L6S-G∼ <cite>Hehemann2012</cite>.

== Kinetics and Mechanism ==
A potential retaining mechanism of this glycoside hydrolase family can be inferred from analogy to clan [{{CAZyDBlink}}Glycoside-Hydrolases.html GH-A enzymes], and is confirmed by structural analyses of a product complex showing an arrangement of the putative catalytic residues that is in agreement with the double displacement mechanism <cite>Hehemann2012</cite>. However, no mechanistic or kinetic analysis demonstrating the stereochemical outcome of the reaction have been reported for this family to date.

== Catalytic Residues ==
The catalytic residues can be inferred from the crystal structure and by analogy to clan GH-A enzymes as two glutamate residues, which are Glu152 (acid/base) and Glu279 (nucleophile) in BpGH86A from ''B. plebeius'' <cite>Hehemann2012</cite>.

== Three-dimensional structures ==
The first 3D structure was determined in 2012 by <cite>Hehemann2012</cite> et al. In agreement with distant sequence homology to clan [{{CAZyDBlink}}Glycoside-Hydrolases.html GH-A enzymes], the overall topology contains an N-terminal (β/α)<sub>8</sub> barrel. However the enzyme architecture is more complex and contains two additional Cterminal β-sandwich domains, which align via their convex faces to the exterior of the (β/α)<sub>8</sub> barrel and connect with two N-terminal β-strands that become part of these C-terminal β-sandwich domains.

== Family Firsts ==
;Identification of first family member: The first member of this family, AgrA, was identified in ''Pseudoalteromonas atlantica'' <cite>Belas1989</cite>.
;First stereochemistry determination: the retaining mechanism is inferred from the arrangement of the most probable catalytic residues in the crystal structure of a product complex <cite>Hehemann2012</cite>.
;First catalytic nucleophile identification: Glu279 in BpGH86A from ''B.plebeius''.
;First general acid/base residue identification: Glu152 in BpGH86A from ''B.plebeius''.
;First 3-D structure: The crystal structure of BpGH86A from ''B.plebeius'', ([{{PDBlink}}4aw7 PDB 4aw7]).

== References ==
<biblio>
#Belas1989 pmid=2914859
#Ohta2004 pmid=15490156
#Ekborg2006 pmid=16672483
#Hehemann2012 pmid=23150581
#Ariga2012 pmid=22814498
</biblio>

[[Category:Glycoside Hydrolase Families|GH086]]

Glycoside Hydrolase Family 86

2014-01-06T08:18:08Z

Mirjam Czjzek: /* Substrate specificities */

{{CuratorApproved}}
* [[Author]]: ^^^Mirjam Czjzek^^^
* [[Responsible Curator]]: ^^^Mirjam Czjzek^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH86'''
|-
|'''Clan'''
|GH-A
|-
|'''Mechanism'''
|probably retaining
|-
|'''Active site residues'''
|inferred from clan GH-A as two Glu
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}GH86.html
|}
</div>


== Substrate specificities ==
[[Glycoside hydrolases]] of family 86 have first been identified to be β-agarases (EC [{{EClink}}3.2.1.81 3.2.1.81]) that cleave β-1,4 glycosidic bonds of agarose. This polysacchride chain is ideally made of alternating α-1,3-linked 3,6-anhydro-L-galactose (LA) and β-1,4-linked D-galactose (G) residues forming a parallel double helix. Four agarolytic enzymes have been characterized: AgrA from ''Pseudoalteromonas atlantica'', AgaO from ''Microbulbifer thermotolerans JAMB-A94'', Aga86E from ''Saccharophagus degradans 2-40'' <cite>Belas1989,Ohta2004,Ekborg2006</cite> and more recently a GH86 β-agarase from a non marine ''Vibrio'' species (sp. OA-2007)<cite>Ariga2012</cite>. AgaO from ''M. thermotolerans'' was reported to be an endo-hydrolytic enzyme, releasing neoagaro-hexaose as main product <cite>Ohta2004</cite>, while the recombinant Aga86E from ''S. degradans'' released only neoagarobiose in an exo-acting manner <cite>Ekborg2006</cite>. In june 2012, a first GH86 enzyme was identified in the human gut Bacteroidetes ''B. plebeius'' that was active on porphyran, an agarocolloïd in which the 3,6-anhydro-L-galactose unit (LA) of neutral agarose is replaced by L-galactose-6-sulfate (L6S). The endo-acting enzyme, BpGH86A, is inactive on agarose and the main products released by cleavage of β-1,4 glycosidic bonds of porphyran, are tetrasaccharides having the sequence L6S-G-L6S-G∼ <cite>Hehemann2012</cite>.

== Kinetics and Mechanism ==
A potential retaining mechanism of this glycoside hydrolase family can be inferred from analogy to clan [{{CAZyDBlink}}Glycoside-Hydrolases.html GH-A enzymes], and is confirmed by structural analyses of a product complex showing an arrangement of the putative catalytic residues that is in agreement with the double displacement mechanism <cite>Hehemann2012</cite>. However, no mechanistic or kinetic analysis demonstrating the stereochemical outcome of the reaction have been reported for this family to date.

== Catalytic Residues ==
The catalytic residues can be inferred from the crystal structure and by analogy to clan GH-A enzymes as two glutamate residues, which are Glu152 (acid/base) and Glu279 (nucleophile) in BpGH86A from ''B. plebeius'' <cite>Hehemann2012</cite>.

== Three-dimensional structures ==
The first 3D structure was determined in 2012 by <cite>Hehemann2012</cite> et al. In agreement with distant sequence homology to clan [{{CAZyDBlink}}Glycoside-Hydrolases.html GH-A enzymes], the overall topology contains an N-terminal (β/α)<sub>8</sub> barrel. However the enzyme architecture is more complex and contains two additional Cterminal β-sandwich domains, which align via their convex faces to the exterior of the (β/α)<sub>8</sub> barrel and connect with two N-terminal β-strands that become part of these C-terminal β-sandwich domains.

== Family Firsts ==
;Identification of first family member: The first member of this family, AgrA, was identified in ''Pseudoalteromonas atlantica'' <cite>Belas1989</cite>.
;First stereochemistry determination: the retaining mechanism is inferred from the arrangement of the most probable catalytic residues in the crystal structure of a product complex <cite>Hehemann2012</cite>.
;First catalytic nucleophile identification: Glu279 in BpGH86A from ''B.plebeius''.
;First general acid/base residue identification: Glu152 in BpGH86A from ''B.plebeius''.
;First 3-D structure: The crystal structure of BpGH86A from ''B.plebeius'', ([{{PDBlink}}4aw7 PDB 4aw7]).

== References ==
<biblio>
#Belas1989 pmid=2914859
#Ohta2004 pmid=15490156
#Ekborg2006 pmid=16672483
#Hehemann2012 pmid=23150581
#Ariga2012 pmid=22814498
</biblio>

[[Category:Glycoside Hydrolase Families|GH086]]

Glycoside Hydrolase Family 86

2014-01-06T08:07:48Z

Mirjam Czjzek: /* Substrate specificities */

{{CuratorApproved}}
* [[Author]]: ^^^Mirjam Czjzek^^^
* [[Responsible Curator]]: ^^^Mirjam Czjzek^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH86'''
|-
|'''Clan'''
|GH-A
|-
|'''Mechanism'''
|probably retaining
|-
|'''Active site residues'''
|inferred from clan GH-A as two Glu
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}GH86.html
|}
</div>


== Substrate specificities ==
[[Glycoside hydrolases]] of family 86 have first been identified to be β-agarases (EC [{{EClink}}3.2.1.81 3.2.1.81]) that cleave β-1,4 glycosidic bonds of agarose. This polysacchride chain is ideally made of alternating α-1,3-linked D-galactose (G) and β-1,4-linked 3,6-anhydro-L-galactose (LA) residues forming a parallel double helix. Four agarolytic enzymes have been characterized: AgrA from ''Pseudoalteromonas atlantica'', AgaO from ''Microbulbifer thermotolerans JAMB-A94'', Aga86E from ''Saccharophagus degradans 2-40'' <cite>Belas1989,Ohta2004,Ekborg2006</cite> and more recently a GH86 β-agarase from a non marine ''Vibrio'' species (sp. OA-2007)<cite>Ariga2012</cite>. AgaO from ''M. thermotolerans'' was reported to be an endo-hydrolytic enzyme, releasing neoagaro-hexaose as main product <cite>Ohta2004</cite>, while the recombinant Aga86E from ''S. degradans'' released only neoagarobiose in an exo-acting manner <cite>Ekborg2006</cite>. In june 2012, a first GH86 enzyme was identified in the human gut Bacteroidetes ''B. plebeius'' that was active on porphyran, an agarocolloïd in which the 3,6-anhydro-L-galactose unit (LA) of neutral agarose is replaced by L-galactose-6-sulfate (L6S). The endo-acting enzyme, BpGH86A, is inactive on agarose and the main products released by cleavage of β-1,4 glycosidic bonds of porphyran, are tetrasaccharides having the sequence L6S-G-L6S-G∼ <cite>Hehemann2012</cite>.

== Kinetics and Mechanism ==
A potential retaining mechanism of this glycoside hydrolase family can be inferred from analogy to clan [{{CAZyDBlink}}Glycoside-Hydrolases.html GH-A enzymes], and is confirmed by structural analyses of a product complex showing an arrangement of the putative catalytic residues that is in agreement with the double displacement mechanism <cite>Hehemann2012</cite>. However, no mechanistic or kinetic analysis demonstrating the stereochemical outcome of the reaction have been reported for this family to date.

== Catalytic Residues ==
The catalytic residues can be inferred from the crystal structure and by analogy to clan GH-A enzymes as two glutamate residues, which are Glu152 (acid/base) and Glu279 (nucleophile) in BpGH86A from ''B. plebeius'' <cite>Hehemann2012</cite>.

== Three-dimensional structures ==
The first 3D structure was determined in 2012 by <cite>Hehemann2012</cite> et al. In agreement with distant sequence homology to clan [{{CAZyDBlink}}Glycoside-Hydrolases.html GH-A enzymes], the overall topology contains an N-terminal (β/α)<sub>8</sub> barrel. However the enzyme architecture is more complex and contains two additional Cterminal β-sandwich domains, which align via their convex faces to the exterior of the (β/α)<sub>8</sub> barrel and connect with two N-terminal β-strands that become part of these C-terminal β-sandwich domains.

== Family Firsts ==
;Identification of first family member: The first member of this family, AgrA, was identified in ''Pseudoalteromonas atlantica'' <cite>Belas1989</cite>.
;First stereochemistry determination: the retaining mechanism is inferred from the arrangement of the most probable catalytic residues in the crystal structure of a product complex <cite>Hehemann2012</cite>.
;First catalytic nucleophile identification: Glu279 in BpGH86A from ''B.plebeius''.
;First general acid/base residue identification: Glu152 in BpGH86A from ''B.plebeius''.
;First 3-D structure: The crystal structure of BpGH86A from ''B.plebeius'', ([{{PDBlink}}4aw7 PDB 4aw7]).

== References ==
<biblio>
#Belas1989 pmid=2914859
#Ohta2004 pmid=15490156
#Ekborg2006 pmid=16672483
#Hehemann2012 pmid=23150581
#Ariga2012 pmid=22814498
</biblio>

[[Category:Glycoside Hydrolase Families|GH086]]

Glycoside Hydrolase Family 86

2014-01-06T08:06:35Z

Mirjam Czjzek: /* Substrate specificities */

{{CuratorApproved}}
* [[Author]]: ^^^Mirjam Czjzek^^^
* [[Responsible Curator]]: ^^^Mirjam Czjzek^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH86'''
|-
|'''Clan'''
|GH-A
|-
|'''Mechanism'''
|probably retaining
|-
|'''Active site residues'''
|inferred from clan GH-A as two Glu
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}GH86.html
|}
</div>


== Substrate specificities ==
[[Glycoside hydrolases]] of family 86 have first been identified to be β-agarases (EC [{{EClink}}3.2.1.81 3.2.1.81]) that cleave β-1,4 glycosidic bonds of agarose. This polysacchride chain is ideally made of alternating β-1,3-linked D-galactose (G) and α-1,4-linked 3,6-anhydro-L-galactose (LA) residues forming a parallel double helix. Four agarolytic enzymes have been characterized: AgrA from ''Pseudoalteromonas atlantica'', AgaO from ''Microbulbifer thermotolerans JAMB-A94'', Aga86E from ''Saccharophagus degradans 2-40'' <cite>Belas1989,Ohta2004,Ekborg2006</cite> and more recently a GH86 β-agarase from a non marine ''Vibrio'' species (sp. OA-2007)<cite>Ariga2012</cite>. AgaO from ''M. thermotolerans'' was reported to be an endo-hydrolytic enzyme, releasing neoagaro-hexaose as main product <cite>Ohta2004</cite>, while the recombinant Aga86E from ''S. degradans'' released only neoagarobiose in an exo-acting manner <cite>Ekborg2006</cite>. In june 2012, a first GH86 enzyme was identified in the human gut Bacteroidetes ''B. plebeius'' that was active on porphyran, an agarocolloïd in which the 3,6-anhydro-L-galactose unit (LA) of neutral agarose is replaced by L-galactose-6-sulfate (L6S). The endo-acting enzyme, BpGH86A, is inactive on agarose and the main products released by cleavage of β-1,4 glycosidic bonds of porphyran, are tetrasaccharides having the sequence L6S-G-L6S-G∼ <cite>Hehemann2012</cite>.

== Kinetics and Mechanism ==
A potential retaining mechanism of this glycoside hydrolase family can be inferred from analogy to clan [{{CAZyDBlink}}Glycoside-Hydrolases.html GH-A enzymes], and is confirmed by structural analyses of a product complex showing an arrangement of the putative catalytic residues that is in agreement with the double displacement mechanism <cite>Hehemann2012</cite>. However, no mechanistic or kinetic analysis demonstrating the stereochemical outcome of the reaction have been reported for this family to date.

== Catalytic Residues ==
The catalytic residues can be inferred from the crystal structure and by analogy to clan GH-A enzymes as two glutamate residues, which are Glu152 (acid/base) and Glu279 (nucleophile) in BpGH86A from ''B. plebeius'' <cite>Hehemann2012</cite>.

== Three-dimensional structures ==
The first 3D structure was determined in 2012 by <cite>Hehemann2012</cite> et al. In agreement with distant sequence homology to clan [{{CAZyDBlink}}Glycoside-Hydrolases.html GH-A enzymes], the overall topology contains an N-terminal (β/α)<sub>8</sub> barrel. However the enzyme architecture is more complex and contains two additional Cterminal β-sandwich domains, which align via their convex faces to the exterior of the (β/α)<sub>8</sub> barrel and connect with two N-terminal β-strands that become part of these C-terminal β-sandwich domains.

== Family Firsts ==
;Identification of first family member: The first member of this family, AgrA, was identified in ''Pseudoalteromonas atlantica'' <cite>Belas1989</cite>.
;First stereochemistry determination: the retaining mechanism is inferred from the arrangement of the most probable catalytic residues in the crystal structure of a product complex <cite>Hehemann2012</cite>.
;First catalytic nucleophile identification: Glu279 in BpGH86A from ''B.plebeius''.
;First general acid/base residue identification: Glu152 in BpGH86A from ''B.plebeius''.
;First 3-D structure: The crystal structure of BpGH86A from ''B.plebeius'', ([{{PDBlink}}4aw7 PDB 4aw7]).

== References ==
<biblio>
#Belas1989 pmid=2914859
#Ohta2004 pmid=15490156
#Ekborg2006 pmid=16672483
#Hehemann2012 pmid=23150581
#Ariga2012 pmid=22814498
</biblio>

[[Category:Glycoside Hydrolase Families|GH086]]

Carbohydrate Binding Module Family 6

2014-01-06T08:03:14Z

Mirjam Czjzek:

{{UnderConstruction}}
* [[Author]]: ^^^Mirjam Czjzek^^^
* [[Responsible Curator]]: ^^^Mirjam Czjzek^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}CBM6.html
|}
</div>


== Ligand specificities ==
The ligand specificity of the first characterized CBM6, originating from a multimodular xylanase from ''Clostridium thermocellum'', was determined to be xylan <cite>Fernandes1999</cite>, although the results showed that this CBM6 was also able to bind to avicel and acid-swollen cellulose. This was also the first CBM6 for which a 3D structure was determined <cite>Czjzek2001</cite>, and multiple sequence alignments, analyzed in the light of the first 3D structure, already gave clear indications that large diversity in specificity was to be expected among CBM6 modules <cite>Czjzek2001</cite>. The first ligand-bound complex of a xylanase CBM6 (CsCBM6-3) from ''Clostridium stercorarium'' was crystallized by Boraston et al. <cite>Boraston2003</cite>. Remarkably, the characterization and 3D structure of a CBM6 from ''Cellvibrio mixtus'' revealed two distinct binding sites that displayed differential binding specificities <cite>Henshaw2004;Pires2004</cite>. CBM6 modules are in general attached to bacterial or archeal polysaccharide degrading enzymes and can be found attached to xylanases, cellulases, agarases, laminarinases, etc <cite>Michel2009</cite>. Interestingly, modules assigned to the CBM6 family have also been found associated to fungal enzymes and to the α-subunit of the coagulation factor G in horseshoe crabs [http://www.cazy.org/CBM6_eukaryota.html (see the eukarotic CBM6 occurence]). In the latter case, the β-1,3-glucan binding of the C-terminal tandem CBM6s has been demonstrated <cite>Takaki2002</cite>. Those CBM6s having characterized binding specificities cover : both linear and branched/decorated xylan, β-1,4-glucan (or cellulose), mixed-linked β-1,3-1,4-glucan (or lichenan), agarose, β-1,3-glucan (or laminarin) and chitin. Based on phylogenetic analyses of all reported CBM6 sequences in 2009 (a total of 167), four subfamilies have been defined that coincide with classes of substrate binding specificity as follows : subfamily 6a, hemicellulose; subfamily 6b, xylan; subfamily 6c, β-glucans with a variety of linkages; and subfamily 6d, agarose <cite>Abbott2009</cite>.

== Structural Features ==
''Content in this section should include, in paragraph form, a description of:''
* '''Fold:''' Likewise many other CBMs the CBM6 modules, roughly containing 120 amino acids, display the overall fold of a β-sandwich, predominantly consisting of five antiparallel β-strands on one face and four antiparallel β-strands on the other face, connected by loops with variable lengths. Within the hierarchal CATH classification the modules belong to the jelly-roll superfamily [http://www.cathdb.info/version/3.5/superfamily/2.60.120.260 2.60.120.260] called "galactose-binding domain-like" that contains 515 unique domains.
* '''Type:''' Due to the existance of the dual binding sites in CBM6s, both Type B and C binding properties have been observed for individual CBM6s.
* '''Features of ligand binding:''' The first identified ligand binding site was not, as usual, located at a shallow cleft on the concave surface of the β-sheets (binding site II, formerly called cleft B in CBM6). Alternatively, a binding site was found located at the apex, within the connecting loops of the two β-sheets (binding site I, formerly cleft A in CBM6) ([{{PDBlink}}1gmm PDB 1gmm]). Interestingly, some CBM6s display binding affinities for both binding sites ([{{PDBlink}}1uyy PDB 1uyy]), either with distinct specificities for each site ([{{PDBlink}}1uy0 PDB 1uy0] and [{{PDBlink}}1uyz PDB 1uyz]) or synergistic binding involving both sites at the same time <cite>Pires2004</cite>, while binding properties of other CBM6s make use of only one binding site, which is in general site I at the apex (i.e. [{{PDBlink}}1uxx PDB 1uxx];[{{PDBlink}}1nae PDB 1nae];[{{PDBlink}}1w9w PDB 1w9w]). The apex site I is made up of two important, highly conserved aromatic residues (mostly W and Y) that "sandwich" a sugar monomer <cite>Czjzek2001;Abbott2009</cite>. These conserved residues are neighboured by a much more variable loop (defined as zone E in Abbott et al. <cite>Abbott2009</cite>) that make up the diversity in binding specificity. Consistantly, a variable number of sugar-binding subites have been observed for site I, ranging from one (end binder) up to five binding subsites. The precise structural and energetic contributions of four of the binding subsites have been dissected, for the first time, in detail by combining crystallography and ITC in the case of the ''Clostridium stercorarium ''CsCBM6-1 <cite>Lammerts2004</cite>. To date, only one CBM6 has been structurally and biochemically characterized that makes use of binding site II, which is the CBM6 from ''Cellvibrio mixtus'' <cite>Henshaw2004;Pires2004</cite> ([{{PDBlink}}1uxz PDB 1uxz]). An updated list of all available three-dimensional structures is accessible at the [http://www.cazy.org/CBM6_structure.html Cazy CBM6 structures page].

== Functionalities ==
''Content in this section should include, in paragraph form, a description of:''
* '''Functional role of CBM:''' The predominant functional role to date described for CBM6 modules is carbohydrate binding and targeting. It has been shown that this type of module synergistically enhances the activity of the adjacent catalytic domain on insoluble substrates.
* '''Most Common Associated Modules:''' 1. xylanases, lichenases, β-agarases, laminarinases, deacetylases; 2. dockerins and coagulation factors.
* '''Novel Applications:''' The CBM6 from ''Clostridium thermocellum'' has been used to label plant tissues <cite>McCartney2004</cite>.

== Family Firsts ==
;First Identified
:The xylose binding CBM6 from a multi-modular xylanase/actetyl-esterase from ''Clostridium thermocellum'' (CtCBM6) was the first to be identified and biochemically characterized. To a lesser extent the module was also able to bind to avicel and acid-swollen cellulose <cite>Fernandes1999</cite>.
;First Structural Characterization
:The same xylose binding CBM6 from ''Clostridium thermocellum'' ([{{PDBlink}}1gmm PDB 1gmm]) was also the first structurally characterized CBM6. The 3D structure revealed that the location of the ligand-binding site of carbohydrate-binding modules that have evolved from a common sequence was not conserved <cite>Czjzek2001</cite>. The first CBM6 in complex with its ligand was determined for the CsCBM6-3 from ''Clostridium stercorarium'' ([{{PDBlink}}1o8p PDB 1o8p])<cite>Boraston2003</cite>.
== References ==
<biblio>
#Fernandes1999 pmid=10432306
#Czjzek2001 pmid=11673472
#Boraston2003 pmid=12634060
#Henshaw2004 pmid=15004011
#Pires2004 pmid=15010454
#Michel2009 pmid=19240276
#Takaki2002 pmid=11830593
#Abbott2009 pmid=19788273
#Lammerts2004 pmid=15223327
#McCartney2004 pmid=14769335

</biblio>

[[Category:Carbohydrate Binding Module Families|CBM006]]

Carbohydrate Binding Module Family 6

2014-01-06T08:00:07Z

Mirjam Czjzek:

{{UnderConstruction}}
* [[Author]]: ^^^Mirjam Czjzek^^^
* [[Responsible Curator]]: ^^^Mirjam Czjzek^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}CBM6.html
|}
</div>


== Ligand specificities ==
The ligand specificity of the first characterized CBM6, originating from a multimodular xylanase from ''Clostridium thermocellum'', was determined to be xylan <cite>Fernandes1999</cite>, although the results showed that this CBM6 was also able to bind to avicel and acid-swollen cellulose. This was also the first CBM6 for which a 3D structure was determined <cite>Czjzek2001</cite>, and multiple sequence alignments, analyzed in the light of the first 3D structure, already gave clear indications that large diversity in specificity was to be expected among CBM6 modules <cite>Czjzek2001</cite>. The first ligand-bound complex of a xylanase CBM6 (CsCBM6-3) from ''Clostridium stercorarium'' was crystallized by Boraston et al. <cite>Boraston2003</cite>. Remarkably, the characterization and 3D structure of a CBM6 from ''Cellvibrio mixtus'' revealed two distinct binding sites that displayed differential binding specificities <cite>Henshaw2004;Pires2004</cite>. CBM6 modules are in general attached to bacterial or archeal polysaccharide degrading enzymes and can be found attached to xylanases, cellulases, agarases, laminarinases, etc <cite>Michel2009</cite>. Interestingly, modules assigned to the CBM6 family have also been found associated to fungal enzymes and to the α-subunit of the coagulation factor G in horseshoe crabs [http://www.cazy.org/CBM6_eukaryota.html (see the eukarotic CBM6 occurence]). In the latter case, the β-1,3-glucan binding of the C-terminal tandem CBM6s has been demonstrated <cite>Takaki2002</cite>. Those CBM6s having characterized binding specificities cover : both linear and branched/decorated xylan, β-1,4-glucan (or cellulose), mixed-linked β-1,3-1,4-glucan (or lichenan), agarose, β-1,3-glucan (or laminarin) and chitin. Based on phylogenetic analyses of all reported CBM6 sequences in 2009 (a total of 167), four subfamilies have been defined that coincide with classes of substrate binding specificity as follows : subfamily 6a, hemicellulose; subfamily 6b, xylan; subfamily 6c, β-glucans with a variety of linkages; and subfamily 6d, agarose <cite>Abbott2009</cite>.

== Structural Features ==
''Content in this section should include, in paragraph form, a description of:''
* '''Fold:''' Likewise many other CBMs the CBM6 modules, roughly containing 120 amino acids, display the overall fold of a β-sandwich, predominantly consisting of five antiparallel β-strands on one face and four antiparallel β-strands on the other face, connected by loops with variable lengths. Within the hierarchal CATH classification the modules belong to the jelly-roll superfamily [http://www.cathdb.info/version/3.5/superfamily/2.60.120.260 2.60.120.260] called "galactose-binding domain-like" that contains 515 unique domains.
* '''Type:''' Due to the existance of the dual binding sites in CBM6s, both Type B and C binding properties have been observed for individual CBM6s.
* '''Features of ligand binding:''' The first identified ligand binding site was not, as usual, located at a shallow cleft on the concave surface of the β-sheets (binding site II, formerly called cleft B in CBM6). Alternatively, a binding site was found located at the apex, within the connecting loops of the two β-sheets (binding site I, formerly cleft A in CBM6) ([{{PDBlink}}1gmm PDB 1gmm]). Interestingly, some CBM6s display binding affinities for both binding sites ([{{PDBlink}}1uyy PDB 1uyy]), either with distinct specificities for each site ([{{PDBlink}}1uy0 PDB 1uy0] and [{{PDBlink}}1uyz PDB 1uyz]) or synergistic binding involving both sites at the same time <cite>Pires2004</cite>, while binding properties of other CBM6s make use of only one binding site, which is in general site I at the apex (i.e. [{{PDBlink}}1uxx PDB 1uxx];[{{PDBlink}}1nae PDB 1nae];[{{PDBlink}}1w9w PDB 1w9w]). The apex site I is made up of two important, highly conserved aromatic residues (mostly W and Y) that "sandwich" a sugar monomer <cite>Czjzek2001;Abbott2009</cite>. These conserved residues are neighboured by a much more variable loop (defined as zone E in Abbott et al. <cite>Abbott2009</cite>) that make up the diversity in binding specificity. Consistantly, a variable number of sugar-binding subites have been observed for site I, ranging from one (end binder) up to five binding subsites. The precise structural and energetic contributions of four of the binding subsites have been dissected, for the first time, in detail by combining crystallography and ITC in the case of the ''Clostridium stercorarium ''CsCBM6-1 <cite>Lammerts2004</cite>. To date, only one CBM6 has been structuraly and biochemically characterized that makes use of binding site II, which is the CBM6 from ''Cellvibrio mixtus'' <cite>Henshaw2004;Pires2004</cite> ([{{PDBlink}}1uxz PDB 1uxz]). An updated list of all available three-dimensional structures is accessible at the [http://www.cazy.org/CBM6_structure.html Cazy CBM6 structures page].

== Functionalities ==
''Content in this section should include, in paragraph form, a description of:''
* '''Functional role of CBM:''' The predominant functional role to date described for CBM6 modules is carbohydrate binding and targeting. It has been shown that this type of module synergistically enhances the activity of the adjacent catalytic domain on insoluble substrates.
* '''Most Common Associated Modules:''' 1. xylanases, lichenases, β-agarases, laminarinases, deacetylases; 2. dockerins and coagulation factors.
* '''Novel Applications:''' The CBM6 from ''Clostridium thermocellum'' has been used to label plant tissues <cite>McCartney2004</cite>.

== Family Firsts ==
;First Identified
:The xylose binding CBM6 from a multi-modular xylanase/actetyl-esterase from ''Clostridium thermocellum'' (CtCBM6) was the first to be identified and biochemically characterized. To a lesser extent the module was also able to bind to avicel and acid-swollen cellulose <cite>Fernandes1999</cite>.
;First Structural Characterization
:The same xylose binding CBM6 from ''Clostridium thermocellum'' ([{{PDBlink}}1gmm PDB 1gmm]) was also the first structuraly characterized CBM6. The 3D structure revealed that the location of the ligand-binding site of carbohydrate-binding modules that have evolved from a common sequence was not conserved <cite>Czjzek2001</cite>. The first CBM6 in complex with its ligand was determined for the CsCBM6-3 from ''Clostridium stercorarium'' ([{{PDBlink}}1o8p PDB 1o8p])<cite>Boraston2003</cite>.
== References ==
<biblio>
#Fernandes1999 pmid=10432306
#Czjzek2001 pmid=11673472
#Boraston2003 pmid=12634060
#Henshaw2004 pmid=15004011
#Pires2004 pmid=15010454
#Michel2009 pmid=19240276
#Takaki2002 pmid=11830593
#Abbott2009 pmid=19788273
#Lammerts2004 pmid=15223327
#McCartney2004 pmid=14769335

</biblio>

[[Category:Carbohydrate Binding Module Families|CBM006]]

Carbohydrate Binding Module Family 6

2014-01-06T07:59:20Z

Mirjam Czjzek:

{{UnderConstruction}}
* [[Author]]: ^^^Mirjam Czjzek^^^
* [[Responsible Curator]]: ^^^Mirjam Czjzek^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}CBM6.html
|}
</div>


== Ligand specificities ==
The ligand specificity of the first characterized CBM6, originating from a multimodular xylanase from ''Clostridium thermocellum'', was determined to be xylan <cite>Fernandes1999</cite>, although the results showed that this CBM6 was also able to bind to avicel and acid-swollen cellulose. This was also the first CBM6 for which a 3D structure was determined <cite>Czjzek2001</cite>, and multiple sequence alignments, analyzed in the light of the first 3D structure, already gave clear indications that large diversity in specificity was to be expected among CBM6 modules <cite>Czjzek2001</cite>. The first ligand-bound complex of a xylanase CBM6 (CsCBM6-3) from ''Clostridium stercorarium'' was crystallized by Boraston et al. <cite>Boraston2003</cite>. Remarkably, the characterization and 3D structure of a CBM6 from ''Cellvibrio mixtus'' revealed two distinct binding sites that displayed differential binding specificities <cite>Henshaw2004;Pires2004</cite>. CBM6 modules are in general attached to bacterial or archeal polysaccharide degrading enzymes and can be found attached to xylanases, cellulases, agarases, laminarinases, etc <cite>Michel2009</cite>. Interestingly, modules assigned to the CBM6 family have also been found associated to fungal enzymes and to the α-subunit of the coagulation factor G in horseshoe crabs [http://www.cazy.org/CBM6_eukaryota.html (see the eukarotic CBM6 occurence]). In the latter case, the β-1,3-glucan binding of the C-terminal tandem CBM6s has been demonstrated <cite>Takaki2002</cite>. Those CBM6s having characterized binding specificities cover : both linear and branched/decorated xylan, β-1,4-glucan (or cellulose), mixed-linked β-1,3-1,4-glucan (or lichenan), agarose, β-1,3-glucan (or laminarin) and chitin. Based on phylogenetic analyses of all reported CBM6 sequences in 2009 (a total of 167), four subfamilies have been defined that coincide with classes of substrate binding specificity as follows : subfamily 6a, hemicellulose; subfamily 6b, xylan; subfamily 6c, β-glucans with a variety of linkages; and subfamily 6d, agarose <cite>Abbott2009</cite>.

== Structural Features ==
''Content in this section should include, in paragraph form, a description of:''
* '''Fold:''' Likewise many other CBMs the CBM6 modules, roughly containing 120 amino acids, display the overall fold of a β-sandwich, predominantly consisting of five antiparallel β-strands on one face and four antiparallel β-strands on the other face, connected by loops with variable lengths. Within the hierarchal CATH classification the modules belong to the jelly-roll superfamily [http://www.cathdb.info/version/3.5/superfamily/2.60.120.260 2.60.120.260] called "galactose-binding domain-like" that contains 515 unique domains.
* '''Type:''' Due to the existance of the dual binding sites in CBM6s, both Type B and C binding properties have been observed for individual CBM6s.
* '''Features of ligand binding:''' The first identified ligand binding site was not, as usual, located at a shallow cleft on the concave surface of the β-sheets (binding site II, formerly called cleft B in CBM6). Alternatively, a binding site was found located at the apex, within the connecting loops of the two β-sheets (binding site I, formerly cleft A in CBM6) ([{{PDBlink}}1gmm PDB 1gmm]). Interestingly, some CBM6s display binding affinities for both binding sites ([{{PDBlink}}1uyy PDB 1uyy]), either with distinct specificities for each site ([{{PDBlink}}1uy0 PDB 1uy0] and [{{PDBlink}}1uyz PDB 1uyz]) or synergistic binding involving both sites at the same time <cite>Pires2004</cite>, while binding properties of other CBM6s make use of only one binding site, which is in general site I at the apex (i.e. [{{PDBlink}}1uxx PDB 1uxx];[{{PDBlink}}1nae PDB 1nae];[{{PDBlink}}1w9w PDB 1w9w]). The apex site I is made up of two important, highly conserved aromatic residues (mostly W and Y) that "sandwich" a sugar monomer <cite>Czjzek2001;Abbott2009</cite>. These conserved residues are neighboured by a much more variable loop (defined as zone E in Abbott et al. <cite>Abbott2009</cite>) that make up the diversity in binding specificity. Consistantly, a variable number of sugar-binding subites have been observed for site I, ranging from one (end binder) up to five binding subsites. The precise structural and energetic contributions of four of the binding subsites have been dissected, for the first time, in detail by combining crystallography and ITC in the case of the ''Clostridium stercorarium ''CsCBM6-1 <cite>Lammerts2004</cite>. To date, only one CBM6 has been structuraly and biochemically characterized that makes use of binding site II, which is the CBM6 from ''Cellvibrio mixtus'' <cite>Henshaw2004;Pires2004</cite> ([{{PDBlink}}1uxz PDB 1uxz]). An updated list of all available three-dimensional structures is accessible at the [http://www.cazy.org/CBM6_structure.html (Cazy CBM6 structures page)].

== Functionalities ==
''Content in this section should include, in paragraph form, a description of:''
* '''Functional role of CBM:''' The predominant functional role to date described for CBM6 modules is carbohydrate binding and targeting. It has been shown that this type of module synergistically enhances the activity of the adjacent catalytic domain on insoluble substrates.
* '''Most Common Associated Modules:''' 1. xylanases, lichenases, β-agarases, laminarinases, deacetylases; 2. dockerins and coagulation factors.
* '''Novel Applications:''' The CBM6 from ''Clostridium thermocellum'' has been used to label plant tissues <cite>McCartney2004</cite>.

== Family Firsts ==
;First Identified
:The xylose binding CBM6 from a multi-modular xylanase/actetyl-esterase from ''Clostridium thermocellum'' (CtCBM6) was the first to be identified and biochemically characterized. To a lesser extent the module was also able to bind to avicel and acid-swollen cellulose <cite>Fernandes1999</cite>.
;First Structural Characterization
:The same xylose binding CBM6 from ''Clostridium thermocellum'' ([{{PDBlink}}1gmm PDB 1gmm]) was also the first structuraly characterized CBM6. The 3D structure revealed that the location of the ligand-binding site of carbohydrate-binding modules that have evolved from a common sequence was not conserved <cite>Czjzek2001</cite>. The first CBM6 in complex with its ligand was determined for the CsCBM6-3 from ''Clostridium stercorarium'' ([{{PDBlink}}1o8p PDB 1o8p])<cite>Boraston2003</cite>.
== References ==
<biblio>
#Fernandes1999 pmid=10432306
#Czjzek2001 pmid=11673472
#Boraston2003 pmid=12634060
#Henshaw2004 pmid=15004011
#Pires2004 pmid=15010454
#Michel2009 pmid=19240276
#Takaki2002 pmid=11830593
#Abbott2009 pmid=19788273
#Lammerts2004 pmid=15223327
#McCartney2004 pmid=14769335

</biblio>

[[Category:Carbohydrate Binding Module Families|CBM006]]

Carbohydrate Binding Module Family 6

2014-01-06T07:56:42Z

Mirjam Czjzek:

{{UnderConstruction}}
* [[Author]]: ^^^Mirjam Czjzek^^^
* [[Responsible Curator]]: ^^^Mirjam Czjzek^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}CBM6.html
|}
</div>


== Ligand specificities ==
The ligand specificity of the first characterized CBM6, originating from a multimodular xylanase from ''Clostridium thermocellum'', was determined to be xylan <cite>Fernandes1999</cite>, although the results showed that this CBM6 was also able to bind to avicel and acid-swollen cellulose. This was also the first CBM6 for which a 3D structure was determined <cite>Czjzek2001</cite>, and multiple sequence alignments, analyzed in the light of the first 3D structure, already gave clear indications that large diversity in specificity was to be expected among CBM6 modules <cite>Czjzek2001</cite>. The first ligand-bound complex of a xylanase CBM6 (CsCBM6-3) from ''Clostridium stercorarium'' was crystallized by Boraston et al. <cite>Boraston2003</cite>. Remarkably, the characterization and 3D structure of a CBM6 from ''Cellvibrio mixtus'' revealed two distinct binding sites that displayed differential binding specificities <cite>Henshaw2004;Pires2004</cite>. CBM6 modules are in general attached to bacterial or archeal polysaccharide degrading enzymes and can be found attached to xylanases, cellulases, agarases, laminarinases, etc <cite>Michel2009</cite>. Interestingly, modules assigned to the CBM6 family have also been found associated to fungal enzymes and to the α-subunit of the coagulation factor G in horseshoe crabs [http://www.cazy.org/CBM6_eukaryota.html (see the eukarotic CBM6 occurence]). In the latter case, the β-1,3-glucan binding of the C-terminal tandem CBM6s has been demonstrated <cite>Takaki2002</cite>. Those CBM6s having characterized binding specificities cover : both linear and branched/decorated xylan, β-1,4-glucan (or cellulose), mixed-linked β-1,3-1,4-glucan (or lichenan), agarose, β-1,3-glucan (or laminarin) and chitin. Based on phylogenetic analyses of all reported CBM6 sequences in 2009 (a total of 167), four subfamilies have been defined that coincide with classes of substrate binding specificity as follows : subfamily 6a, hemicellulose; subfamily 6b, xylan; subfamily 6c, β-glucans with a variety of linkages; and subfamily 6d, agarose <cite>Abbott2009</cite>.

== Structural Features ==
''Content in this section should include, in paragraph form, a description of:''
* '''Fold:''' Likewise many other CBMs the CBM6 modules, roughly containing 120 amino acids, display the overall fold of a β-sandwich, predominantly consisting of five antiparallel β-strands on one face and four antiparallel β-strands on the other face, connected by loops with variable lengths. Within the hierarchal CATH classification the modules belong to the jelly-roll superfamily [http://www.cathdb.info/version/3.5/superfamily/2.60.120.260 2.60.120.260] called "galactose-binding domain-like" that contains 515 unique domains.
* '''Type:''' Due to the existance of the dual binding sites in CBM6s, both Type B and C binding properties have been observed for individual CBM6s.
* '''Features of ligand binding:''' The first identified ligand binding site was not, as usual, located at a shallow cleft on the concave surface of the β-sheets (binding site II, formerly called cleft B in CBM6). Alternatively, a binding site was found located at the apex, within the connecting loops of the two β-sheets (binding site I, formerly cleft A in CBM6) ([{{PDBlink}}1gmm PDB 1gmm]). Interestingly, some CBM6s display binding affinities for both binding sites ([{{PDBlink}}1uyy PDB 1uyy]), either with distinct specificities for each site ([{{PDBlink}}1uy0 PDB 1uy0] and [{{PDBlink}}1uyz PDB 1uyz]) or synergistic binding involving both sites at the same time <cite>Pires2004</cite>, while binding properties of other CBM6s make use of only one binding site, which is in general site I at the apex (i.e. [{{PDBlink}}1uxx PDB 1uxx];[{{PDBlink}}1nae PDB 1nae];[{{PDBlink}}1w9w PDB 1w9w]). The apex site I is made up of two important, highly conserved aromatic residues (mostly W and Y) that "sandwich" a sugar monomer <cite>Czjzek2001;Abbott2009</cite>. These conserved residues are neighboured by a much more variable loop (defined as zone E in Abbott et al. <cite>Abbott2009</cite>) that make up the diversity in binding specificity. Consistantly, a variable number of sugar-binding subites have been observed for site I, ranging from one (end binder) up to five binding subsites. The precise structural and energetic contributions of four of the binding subsites have been dissected, for the first time, in detail by combining crystallography and ITC in the case of the ''Clostridium stercorarium ''CsCBM6-1 <cite>Lammerts2004</cite>. To date, only one CBM6 has been structuraly and biochemically characterized that makes use of binding site II, which is the CBM6 from ''Cellvibrio mixtus'' <cite>Henshaw2004;Pires2004</cite> ([{{PDBlink}}1uxz PDB 1uxz]). A full list of

== Functionalities ==
''Content in this section should include, in paragraph form, a description of:''
* '''Functional role of CBM:''' The predominant functional role to date described for CBM6 modules is carbohydrate binding and targeting. It has been shown that this type of module synergistically enhances the activity of the adjacent catalytic domain on insoluble substrates.
* '''Most Common Associated Modules:''' 1. xylanases, lichenases, β-agarases, laminarinases, deacetylases; 2. dockerins and coagulation factors.
* '''Novel Applications:''' The CBM6 from ''Clostridium thermocellum'' has been used to label plant tissues <cite>McCartney2004</cite>.

== Family Firsts ==
;First Identified
:The xylose binding CBM6 from a multi-modular xylanase/actetyl-esterase from ''Clostridium thermocellum'' (CtCBM6) was the first to be identified and biochemically characterized. To a lesser extent the module was also able to bind to avicel and acid-swollen cellulose <cite>Fernandes1999</cite>.
;First Structural Characterization
:The same xylose binding CBM6 from ''Clostridium thermocellum'' ([{{PDBlink}}1gmm PDB 1gmm]) was also the first structuraly characterized CBM6. The 3D structure revealed that the location of the ligand-binding site of carbohydrate-binding modules that have evolved from a common sequence was not conserved <cite>Czjzek2001</cite>. The first CBM6 in complex with its ligand was determined for the CsCBM6-3 from ''Clostridium stercorarium'' ([{{PDBlink}}1o8p PDB 1o8p])<cite>Boraston2003</cite>.
== References ==
<biblio>
#Fernandes1999 pmid=10432306
#Czjzek2001 pmid=11673472
#Boraston2003 pmid=12634060
#Henshaw2004 pmid=15004011
#Pires2004 pmid=15010454
#Michel2009 pmid=19240276
#Takaki2002 pmid=11830593
#Abbott2009 pmid=19788273
#Lammerts2004 pmid=15223327
#McCartney2004 pmid=14769335

</biblio>

[[Category:Carbohydrate Binding Module Families|CBM006]]

Carbohydrate Binding Module Family 6

2014-01-06T07:55:23Z

Mirjam Czjzek:

{{UnderConstruction}}
* [[Author]]: ^^^Mirjam Czjzek^^^
* [[Responsible Curator]]: ^^^Mirjam Czjzek^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}CBM6.html
|}
</div>


== Ligand specificities ==
The ligand specificity of the first characterized CBM6, originating from a multimodular xylanase from ''Clostridium thermocellum'', was determined to be xylan <cite>Fernandes1999</cite>, although the results showed that this CBM6 was also able to bind to avicel and acid-swollen cellulose. This was also the first CBM6 for which a 3D structure was determined <cite>Czjzek2001</cite>, and multiple sequence alignments, analyzed in the light of the first 3D structure, already gave clear indications that large diversity in specificity was to be expected among CBM6 modules <cite>Czjzek2001</cite>. The first ligand-bound complex of a xylanase CBM6 (CsCBM6-3) from ''Clostridium stercorarium'' was crystallized by Boraston et al. <cite>Boraston2003</cite>. Remarkably, the characterization and 3D structure of a CBM6 from ''Cellvibrio mixtus'' revealed two distinct binding sites that displayed differential binding specificities <cite>Henshaw2004;Pires2004</cite>. CBM6 modules are in general attached to bacterial or archeal polysaccharide degrading enzymes and can be found attached to xylanases, cellulases, agarases, laminarinases, etc <cite>Michel2009</cite>. Interestingly, modules assigned to the CBM6 family have also been found associated to fungal enzymes and to the α-subunit of the coagulation factor G in horseshoe crabs [http://www.cazy.org/CBM6_eukaryota.html (see the eukarotic CBM6 occurence]). In the latter case, the β-1,3-glucan binding of the C-terminal tandem CBM6s has been demonstrated <cite>Takaki2002</cite>. Those CBM6s having characterized binding specificities cover : both linear and branched/decorated xylan, β-1,4-glucan (or cellulose), mixed-linked β-1,3-1,4-glucan (or lichenan), agarose, β-1,3-glucan (or laminarin) and chitin. Based on phylogenetic analyses of all reported CBM6 sequences in 2009 (a total of 167), four subfamilies have been defined that coincide with classes of substrate binding specificity as follows : subfamily 6a, hemicellulose; subfamily 6b, xylan; subfamily 6c, β-glucans with a variety of linkages; and subfamily 6d, agarose <cite>Abbott2009</cite>.

== Structural Features ==
''Content in this section should include, in paragraph form, a description of:''
* '''Fold:''' Likewise many other CBMs the CBM6 modules, roughly containing 120 amino acids, display the overall fold of a β-sandwich, predominantly consisting of five antiparallel β-strands on one face and four antiparallel β-strands on the other face, connected by loops with variable lengths. Within the hierarchal CATH classification the modules belong to the jelly-roll superfamily [http://www.cathdb.info/version/3.5/superfamily/2.60.120.260 2.60.120.260] called "galactose-binding domain-like" that contains 515 unique domains.
* '''Type:''' Due to the existance of the dual binding sites in CBM6s, both Type B and C binding properties have been observed for individual CBM6s.
* '''Features of ligand binding:''' The first identified ligand binding site was not, as usual, located at a shallow cleft on the concave surface of the β-sheets (binding site II, formerly called cleft B in CBM6). Alternatively, a binding site was found located at the apex, within the connecting loops of the two β-sheets (binding site I, formerly cleft A in CBM6) ([{{PDBlink}}1gmm PDB 1gmm]). Interestingly, some CBM6s display binding affinities for both binding sites ([{{PDBlink}}1uyy PDB 1uyy]), either with distinct specificities for each site ([{{PDBlink}}1uy0 PDB 1uy0] and [{{PDBlink}}1uyz PDB 1uyz]) or synergistic binding involving both sites at the same time <cite>Pires2004</cite>, while binding properties of other CBM6s make use of only one binding site, which is in general site I at the apex (i.e. [{{PDBlink}}1uxx PDB 1uxx];[{{PDBlink}}1nae PDB 1nae];[{{PDBlink}}1w9w PDB 1w9w]). The apex site I is made up of two important, highly conserved aromatic residues (mostly W and Y) that "sandwich" a sugar monomer <cite>Czjzek2001;Abbott2009</cite>. These conserved residues are neighboured by a much more variable loop (defined as zone E in Abbott et al. <cite>Abbott2009</cite>) that make up the diversity in binding specificity. Consistantly, a variable number of sugar-binding subites have been observed for site I, ranging from one (end binder) up to five binding subsites. The precise structural and energetic contributions of four of the binding subsites have been dissected, for the first time, in detail by combining crystallography and ITC in the case of the ''Clostridium stercorarium ''CsCBM6-1 <cite>Lammerts2004</cite>. To date, only one CBM6 has been structuraly and biochemically characterized that makes use of binding site II, which is the CBM6 from ''Cellvibrio mixtus'' <cite>Henshaw2004;Pires2004</cite> ([{{PDBlink}}1uxz PDB 1uxz])

== Functionalities ==
''Content in this section should include, in paragraph form, a description of:''
* '''Functional role of CBM:''' The predominant functional role to date described for CBM6 modules is carbohydrate binding and targeting. It has been shown that this type of module synergistically enhances the activity of the adjacent catalytic domain on insoluble substrates.
* '''Most Common Associated Modules:''' 1. xylanases, lichenases, β-agarases, laminarinases, deacetylases; 2. dockerins and coagulation factors.
* '''Novel Applications:''' The CBM6 from ''Clostridium thermocellum'' has been used to label plant tissues <cite>McCartney2004</cite>.

== Family Firsts ==
;First Identified
:The xylose binding CBM6 from a multi-modular xylanase/actetyl-esterase from ''Clostridium thermocellum'' (CtCBM6) was the first to be identified and biochemically characterized. To a lesser extent the module was also able to bind to avicel and acid-swollen cellulose <cite>Fernandes1999</cite>.
;First Structural Characterization
:The same xylose binding CBM6 from ''Clostridium thermocellum'' ([{{PDBlink}}1gmm PDB 1gmm]) was also the first structuraly characterized CBM6. The 3D structure revealed that the location of the ligand-binding site of carbohydrate-binding modules that have evolved from a common sequence was not conserved <cite>Czjzek2001</cite>. The first CBM6 in complex with its ligand was determined for the CsCBM6-3 from ''Clostridium stercorarium'' ([{{PDBlink}}1o8p PDB 1o8p])<cite>Boraston2003</cite>.
== References ==
<biblio>
#Fernandes1999 pmid=10432306
#Czjzek2001 pmid=11673472
#Boraston2003 pmid=12634060
#Henshaw2004 pmid=15004011
#Pires2004 pmid=15010454
#Michel2009 pmid=19240276
#Takaki2002 pmid=11830593
#Abbott2009 pmid=19788273
#Lammerts2004 pmid=15223327
#McCartney2004 pmid=14769335

</biblio>

[[Category:Carbohydrate Binding Module Families|CBM006]]

Carbohydrate Binding Module Family 6

2014-01-05T15:25:47Z

Mirjam Czjzek:

{{UnderConstruction}}
* [[Author]]: ^^^Mirjam Czjzek^^^
* [[Responsible Curator]]: ^^^Mirjam Czjzek^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}CBM6.html
|}
</div>


== Ligand specificities ==
The ligand specificity of the first characterized CBM6, originating from a multimodular xylanase from ''Clostridium thermocellum'', was determined to be xylan <cite>Fernandes1999</cite>, although the results showed that this CBM6 was also able to bind to avicel and acid-swollen cellulose. This was also the first CBM6 for which a 3D structure was determined <cite>Czjzek2001</cite>, and multiple sequence alignments, analyzed in the light of the first 3D structure, already gave clear indications that large diversity in specificity was to be expected among CBM6 modules <cite>Czjzek2001</cite>. Remarkably, the characterization and 3D structure of a CBM6 from ''Cellvibrio mixtus'' revealed two distinct binding sites that displayed differential binding specificities <cite>Henshaw2004;Pires2004</cite>. CBM6 modules are in general attached to bacterial or archeal polysaccharide degrading enzymes and can be found attached to xylanases, cellulases, agarases, laminarinases, etc <cite>Michel2009</cite>. Interestingly, modules assigned to the CBM6 family have also been found associated to fungal enzymes and to the α-subunit of the coagulation factor G in horseshoe crabs [http://www.cazy.org/CBM6_eukaryota.html (see the eukarotic CBM6 occurence]). In the latter case, the β-1,3-glucan binding of the C-terminal tandem CBM6s has been demonstrated <cite>Takaki2002</cite>. Those CBM6s having characterized binding specificities cover : both linear and branched/decorated xylan, β-1,4-glucan (or cellulose), mixed-linked β-1,3-1,4-glucan (or lichenan), agarose, β-1,3-glucan (or laminarin) and chitin. Based on phylogenetic analyses of all reported CBM6 sequences in 2009 (a total of 167), four subfamilies have been defined that coincide with classes of substrate binding specificity as follows : subfamily 6a, hemicellulose; subfamily 6b, xylan; subfamily 6c, β-glucans with a variety of linkages; and subfamily 6d, agarose <cite>Abbott2009</cite>.

== Structural Features ==
''Content in this section should include, in paragraph form, a description of:''
* '''Fold:''' Likewise many other CBMs the CBM6 modules, roughly containing 120 amino acids, display the overall fold of a β-sandwich, predominantly consisting of five antiparallel β-strands on one face and four antiparallel β-strands on the other face, connected by loops with variable lengths. Within the hierarchal CATH classification the modules belong to the jelly-roll superfamily [http://www.cathdb.info/version/3.5/superfamily/2.60.120.260 2.60.120.260] called "galactose-binding domain-like" that contains 515 unique domains.
* '''Type:''' Due to the existance of the dual binding sites in CBM6s, both Type B and C binding properties have been observed for individual CBM6s.
* '''Features of ligand binding:''' The first identified ligand binding site was not, as usual, located at a shallow cleft on the concave surface of the β-sheets (binding site II, formerly called cleft B in CBM6). Alternatively, a binding site was found located at the apex, within the connecting loops of the two β-sheets (binding site I, formerly cleft A in CBM6) ([{{PDBlink}}1gmm PDB 1gmm]). Interestingly, some CBM6s display binding affinities for both binding sites ([{{PDBlink}}1uyy PDB 1uyy]), either with distinct specificities for each site ([{{PDBlink}}1uy0 PDB 1uy0] and [{{PDBlink}}1uyz PDB 1uyz]) or synergistic binding involving both sites at the same time <cite>Pires2004</cite>, while binding properties of other CBM6s make use of only one binding site, which is in general site I at the apex (i.e. [{{PDBlink}}1uxx PDB 1uxx];[{{PDBlink}}1nae PDB 1nae];[{{PDBlink}}1w9w PDB 1w9w]). The apex site I is made up of two important, highly conserved aromatic residues (mostly W and Y) that "sandwich" a sugar monomer <cite>Czjzek2001;Abbott2009</cite>. These conserved residues are neighboured by a much more variable loop (defined as zone E in Abbott et al. <cite>Abbott2009</cite>) that make up the diversity in binding specificity. Consistantly, a variable number of sugar-binding subites have been observed for site I, ranging from one (end binder) up to five binding subsites. The precise structural and energetic contributions of four of the binding subsites have been dissected, for the first time, in detail by combining crystallography and ITC in the case of the ''Clostridium stercorarium ''CsCBM6-1 <cite>Lammerts2004</cite>. To date, only one CBM6 has been structuraly and biochemically characterized that makes use of binding site II, which is the CBM6 from ''Cellvibrio mixtus'' <cite>Henshaw2004;Pires2004</cite> ([{{PDBlink}}1uxz PDB 1uxz])

== Functionalities ==
''Content in this section should include, in paragraph form, a description of:''
* '''Functional role of CBM:''' The predominant functional role to date described for CBM6 modules is carbohydrate binding and targeting. It has been shown that this type of module synergistically enhances the activity of the adjacent catalytic domain on insoluble substrates.
* '''Most Common Associated Modules:''' 1. xylanases, lichenases, β-agarases, laminarinases, deacetylases; 2. dockerins and coagulation factors.
* '''Novel Applications:''' The CBM6 from ''Clostridium thermocellum'' has been used to label plant tissues <cite>McCartney2004</cite>.

== Family Firsts ==
;First Identified
:The xylose binding CBM6 from a multi-modular xylanase/actetyl-esterase from ''Clostridium thermocellum'' (CtCBM6) was the first to be identified and biochemically characterized. To a lesser extent the module was also able to bind to avicel and acid-swollen cellulose <cite>Fernandes1999</cite>.
;First Structural Characterization
:The same xylose binding CBM6 from ''Clostridium thermocellum'' ([{{PDBlink}}1gmm PDB 1gmm]) was also the first structuraly characterized CBM6. The 3D structure revealed that the location of the ligand-binding site of carbohydrate-binding modules that have evolved from a common sequence was not conserved <cite>Czjzek2001</cite>.
== References ==
<biblio>
#Fernandes1999 pmid=10432306
#Czjzek2001 pmid=11673472
#Henshaw2004 pmid=15004011
#Pires2004 pmid=15010454
#Michel2009 pmid=19240276
#Takaki2002 pmid=11830593
#Abbott2009 pmid=19788273
#Lammerts2004 pmid=15223327
#McCartney2004 pmid=14769335

</biblio>

[[Category:Carbohydrate Binding Module Families|CBM006]]

Carbohydrate Binding Module Family 6

2014-01-05T15:25:12Z

Mirjam Czjzek:

{{UnderConstruction}}
* [[Author]]: ^^^Mirjam Czjzek^^^
* [[Responsible Curator]]: ^^^Mirjam Czjzek^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}CBM6.html
|}
</div>


== Ligand specificities ==
The ligand specificity of the first characterized CBM6, originating from a multimodular xylanase from ''Clostridium thermocellum'', was determined to be xylan <cite>Fernandes1999</cite>, although the results showed that this CBM6 was also able to bind to avicel and acid-swollen cellulose. This was also the first CBM6 for which a 3D structure was determined <cite>Czjzek2001</cite>, and multiple sequence alignments, analyzed in the light of the first 3D structure, already gave clear indications that large diversity in specificity was to be expected among CBM6 modules <cite>Czjzek2001</cite>. Remarkably, the characterization and 3D structure of a CBM6 from ''Cellvibrio mixtus'' revealed two distinct binding sites that displayed differential binding specificities <cite>Henshaw2004;Pires2004</cite>. CBM6 modules are in general attached to bacterial or archeal polysaccharide degrading enzymes and can be found attached to xylanases, cellulases, agarases, laminarinases, etc <cite>Michel2009</cite>. Interestingly, modules assigned to the CBM6 family have also been found associated to fungal enzymes and to the α-subunit of the coagulation factor G in horseshoe crabs [http://www.cazy.org/CBM6_eukaryota.html (see the eukarotic CBM6 occurence]). In the latter case, the β-1,3-glucan binding of the C-terminal tandem CBM6s has been demonstrated <cite>Takaki2002</cite>. Those CBM6s having characterized binding specificities cover : both linear and branched/decorated xylan, β-1,4-glucan (or cellulose), mixed-linked β-1,3-1,4-glucan (or lichenan), agarose, β-1,3-glucan (or laminarin) and chitin. Based on phylogenetic analyses of all reported CBM6 sequences in 2009 (a total of 167), four subfamilies have been defined that coincide with classes of substrate binding specificity as follows : subfamily 6a, hemicellulose; subfamily 6b, xylan; subfamily 6c, β-glucans with a variety of linkages; and subfamily 6d, agarose <cite>Abbott2009</cite>.

== Structural Features ==
''Content in this section should include, in paragraph form, a description of:''
* '''Fold:''' Likewise many other CBMs the CBM6 modules, roughly containing 120 amino acids, display the overall fold of a β-sandwich, predominantly consisting of five antiparallel β-strands on one face and four antiparallel β-strands on the other face, connected by loops with variable lengths. Within the hierarchal CATH classification the modules belong to the jelly-roll superfamily [http://www.cathdb.info/version/3.5/superfamily/2.60.120.260 2.60.120.260] called "galactose-binding domain-like" that contains 515 unique domains.
* '''Type:''' Due to the existance of the dual binding sites in CBM6s, both Type B and C binding properties have been observed for individual CBM6s.
* '''Features of ligand binding:''' The first identified ligand binding site was not, as usual, located at a shallow cleft on the concave surface of the β-sheets (binding site II, formerly called cleft B in CBM6). Alternatively, a binding site was found located at the apex, within the connecting loops of the two β-sheets (binding site I, formerly cleft A in CBM6) ([{{PDBlink}}1gmm PDB 1gmm]). Interestingly, some CBM6s display binding affinities for both binding sites ([{{PDBlink}}1uyy PDB 1uyy]), either with distinct specificities for each site ([{{PDBlink}}1uy0 PDB 1uy0] and [{{PDBlink}}1uyz PDB 1uyz]) or synergistic binding involving both sites at the same time <cite>Pires2004</cite>, while binding properties of other CBM6s make use of only one binding site, which is in general site I at the apex (i.e. [{{PDBlink}}1uxx PDB 1uxx];[{{PDBlink}}1nae PDB 1nae];[{{PDBlink}}1w9w PDB 1w9w]). The apex site I is made up of two important, highly conserved aromatic residues (mostly W and Y) that "sandwich" a sugar monomer <cite>Czjzek2001;Abbott2009</cite>. These conserved residues are neighboured by a much more variable loop (defined as zone E in Abbott et al. <cite>Abbott2009</cite>) that make up the diversity in binding specificity. Consistantly, a variable number of sugar-binding subites have been observed for site I, ranging from one (end binder) up to five binding subsites. The precise structural and energetic contributions of four of the binding subsites have been dissected, for the first time, in detail by combining crystallography and ITC in the case of the ''Clostridium stercorarium ''CsCBM6-1 <cite>Lammerts2004</cite>. To date, only one CBM6 has been structuraly and biochemically characterized that makes use of binding site II, which is the CBM6 from ''Cellvibrio mixtus'' <cite>Henshaw2004;Pires2004</cite> ([{{PDBlink}}1uxz PDB 1uxz])

== Functionalities ==
''Content in this section should include, in paragraph form, a description of:''
* '''Functional role of CBM:''' The predominant functional role to date described for CBM6 modules is carbohydrate binding and targeting. It has been shown that this type of module synergistically enhances the activity of the adjacent catalytic domain on insoluble substrates.
* '''Most Common Associated Modules:''' 1. xylanases, lichenases, β-agarases, laminarinases; deacetylases 2. dockerins and coagulation factors.
* '''Novel Applications:''' The CBM6 from ''Clostridium thermocellum'' has been used to label plant tissues <cite>McCartney2004</cite>.

== Family Firsts ==
;First Identified
:The xylose binding CBM6 from a multi-modular xylanase/actetyl-esterase from ''Clostridium thermocellum'' (CtCBM6) was the first to be identified and biochemically characterized. To a lesser extent the module was also able to bind to avicel and acid-swollen cellulose <cite>Fernandes1999</cite>.
;First Structural Characterization
:The same xylose binding CBM6 from ''Clostridium thermocellum'' ([{{PDBlink}}1gmm PDB 1gmm]) was also the first structuraly characterized CBM6. The 3D structure revealed that the location of the ligand-binding site of carbohydrate-binding modules that have evolved from a common sequence was not conserved <cite>Czjzek2001</cite>.
== References ==
<biblio>
#Fernandes1999 pmid=10432306
#Czjzek2001 pmid=11673472
#Henshaw2004 pmid=15004011
#Pires2004 pmid=15010454
#Michel2009 pmid=19240276
#Takaki2002 pmid=11830593
#Abbott2009 pmid=19788273
#Lammerts2004 pmid=15223327
#McCartney2004 pmid=14769335

</biblio>

[[Category:Carbohydrate Binding Module Families|CBM006]]

Carbohydrate Binding Module Family 6

2014-01-05T15:23:31Z

Mirjam Czjzek:

{{UnderConstruction}}
* [[Author]]: ^^^Mirjam Czjzek^^^
* [[Responsible Curator]]: ^^^Mirjam Czjzek^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}CBM6.html
|}
</div>


== Ligand specificities ==
The ligand specificity of the first characterized CBM6, originating from a multimodular xylanase from ''Clostridium thermocellum'', was determined to be xylan <cite>Fernandes1999</cite>, although the results showed that this CBM6 was also able to bind to avicel and acid-swollen cellulose. This was also the first CBM6 for which a 3D structure was determined <cite>Czjzek2001</cite>, and multiple sequence alignments, analyzed in the light of the first 3D structure, already gave clear indications that large diversity in specificity was to be expected among CBM6 modules <cite>Czjzek2001</cite>. Remarkably, the characterization and 3D structure of a CBM6 from ''Cellvibrio mixtus'' revealed two distinct binding sites that displayed differential binding specificities <cite>Henshaw2004;Pires2004</cite>. CBM6 modules are in general attached to bacterial or archeal polysaccharide degrading enzymes and can be found attached to xylanases, cellulases, agarases, laminarinases, etc <cite>Michel2009</cite>. Interestingly, modules assigned to the CBM6 family have also been found associated to fungal enzymes and to the α-subunit of the coagulation factor G in horseshoe crabs [http://www.cazy.org/CBM6_eukaryota.html (see the eukarotic CBM6 occurence]). In the latter case, the β-1,3-glucan binding of the C-terminal tandem CBM6s has been demonstrated <cite>Takaki2002</cite>. Those CBM6s having characterized binding specificities cover : both linear and branched/decorated xylan, β-1,4-glucan (or cellulose), mixed-linked β-1,3-1,4-glucan (or lichenan), agarose, β-1,3-glucan (or laminarin) and chitin. Based on phylogenetic analyses of all reported CBM6 sequences in 2009 (a total of 167), four subfamilies have been defined that coincide with classes of substrate binding specificity as follows : subfamily 6a, hemicellulose; subfamily 6b, xylan; subfamily 6c, β-glucans with a variety of linkages; and subfamily 6d, agarose <cite>Abbott2009</cite>.

== Structural Features ==
''Content in this section should include, in paragraph form, a description of:''
* '''Fold:''' Likewise many other CBMs the CBM6 modules, roughly containing 120 amino acids, display the overall fold of a β-sandwich, predominantly consisting of five antiparallel β-strands on one face and four antiparallel β-strands on the other face, connected by loops with variable lengths. Within the hierarchal CATH classification the modules belong to the jelly-roll superfamily [http://www.cathdb.info/version/3.5/superfamily/2.60.120.260 2.60.120.260] called "galactose-binding domain-like" that contains 515 unique domains.
* '''Type:''' Due to the existance of the dual binding sites in CBM6s, both Type B and C binding properties have been observed for individual CBM6s.
* '''Features of ligand binding:''' The first identified ligand binding site was not, as usual, located at a shallow cleft on the concave surface of the β-sheets (binding site II, formerly called cleft B in CBM6). Alternatively, a binding site was found located at the apex, within the connecting loops of the two β-sheets (binding site I, formerly cleft A in CBM6) ([{{PDBlink}}1gmm PDB 1gmm]). Interestingly, some CBM6s display binding affinities for both binding sites ([{{PDBlink}}1uyy PDB 1uyy]), either with distinct specificities for each site ([{{PDBlink}}1uy0 PDB 1uy0] and [{{PDBlink}}1uyz PDB 1uyz]) or synergistic binding involving both sites at the same time <cite>Pires2004</cite>, while binding properties of other CBM6s make use of only one binding site, which is in general site I at the apex (i.e. [{{PDBlink}}1uxx PDB 1uxx];[{{PDBlink}}1nae PDB 1nae];[{{PDBlink}}1w9w PDB 1w9w]). The apex site I is made up of two important, highly conserved aromatic residues (mostly W and Y) that "sandwich" a sugar monomer <cite>Czjzek2001;Abbott2009</cite>. These conserved residues are neighboured by a much more variable loop (defined as zone E in Abbott et al. <cite>Abbott2009</cite>) that make up the diversity in binding specificity. Consistantly, a variable number of sugar-binding subites have been observed for site I, ranging from one (end binder) up to five binding subsites. The precise structural and energetic contributions of four of the binding subsites have been dissected, for the first time, in detail by combining crystallography and ITC in the case of the ''Clostridium stercorarium ''CsCBM6-1 <cite>Lammerts2004</cite>. To date, only one CBM6 has been structuraly and biochemically characterized that makes use of binding site II, which is the CBM6 from ''Cellvibrio mixtus'' <cite>Henshaw2004;Pires2004</cite> ([{{PDBlink}}1uxz PDB 1uxz])

== Functionalities ==
''Content in this section should include, in paragraph form, a description of:''
* '''Functional role of CBM:''' The predominant functional role to date described for CBM6 modules is carbohydrate binding and targeting. It has been shown that this type of module synergistically enhances the activity of the adjacent catalytic domain on insoluble substrates.
* '''Most Common Associated Modules:''' 1. xylanases, lichenases, β-agarases, laminarinases; 2. dockerins, nodulation (NodB) and coagulation factors.
* '''Novel Applications:''' The CBM6 from ''Clostridium thermocellum'' has been used to label plant tissues <cite>McCartney2004</cite>.

== Family Firsts ==
;First Identified
:The xylose binding CBM6 from a multi-modular xylanase/actetyl-esterase from ''Clostridium thermocellum'' (CtCBM6) was the first to be identified and biochemically characterized. To a lesser extent the module was also able to bind to avicel and acid-swollen cellulose <cite>Fernandes1999</cite>.
;First Structural Characterization
:The same xylose binding CBM6 from ''Clostridium thermocellum'' ([{{PDBlink}}1gmm PDB 1gmm]) was also the first structuraly characterized CBM6. The 3D structure revealed that the location of the ligand-binding site of carbohydrate-binding modules that have evolved from a common sequence was not conserved <cite>Czjzek2001</cite>.
== References ==
<biblio>
#Fernandes1999 pmid=10432306
#Czjzek2001 pmid=11673472
#Henshaw2004 pmid=15004011
#Pires2004 pmid=15010454
#Michel2009 pmid=19240276
#Takaki2002 pmid=11830593
#Abbott2009 pmid=19788273
#Lammerts2004 pmid=15223327
#McCartney2004 pmid=14769335

</biblio>

[[Category:Carbohydrate Binding Module Families|CBM006]]

Carbohydrate Binding Module Family 6

2014-01-05T15:16:55Z

Mirjam Czjzek:

{{UnderConstruction}}
* [[Author]]: ^^^Mirjam Czjzek^^^
* [[Responsible Curator]]: ^^^Mirjam Czjzek^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}CBM6.html
|}
</div>


== Ligand specificities ==
The ligand specificity of the first characterized CBM6, originating from a multimodular xylanase from ''Clostridium thermocellum'', was determined to be xylan <cite>Fernandes1999</cite>, although the results showed that this CBM6 was also able to bind to avicel and acid-swollen cellulose. This was also the first CBM6 for which a 3D structure was determined <cite>Czjzek2001</cite>, and multiple sequence alignments, analyzed in the light of the first 3D structure, already gave clear indications that large diversity in specificity was to be expected among CBM6 modules <cite>Czjzek2001</cite>. Remarkably, the characterization and 3D structure of a CBM6 from ''Cellvibrio mixtus'' revealed two distinct binding sites that displayed differential binding specificities <cite>Henshaw2004;Pires2004</cite>. CBM6 modules are in general attached to bacterial or archeal polysaccharide degrading enzymes and can be found attached to xylanases, cellulases, agarases, laminarinases, etc <cite>Michel2009</cite>. Interestingly, modules assigned to the CBM6 family have also been found associated to fungal enzymes and to the α-subunit of the coagulation factor G in horseshoe crabs [http://www.cazy.org/CBM6_eukaryota.html (see the eukarotic CBM6 occurence]). In the latter case, the β-1,3-glucan binding of the C-terminal tandem CBM6s has been demonstrated <cite>Takaki2002</cite>. Those CBM6s having characterized binding specificities cover : both linear and branched/decorated xylan, β-1,4-glucan (or cellulose), mixed-linked β-1,3-1,4-glucan (or lichenan), agarose, β-1,3-glucan (or laminarin) and chitin. Based on phylogenetic analyses of all reported CBM6 sequences in 2009 (a total of 167), four subfamilies have been defined that coincide with classes of substrate binding specificity as follows : subfamily 6a, hemicellulose; subfamily 6b, xylan; subfamily 6c, β-glucans with a variety of linkages; and subfamily 6d, agarose <cite>Abbott2009</cite>.

== Structural Features ==
''Content in this section should include, in paragraph form, a description of:''
* '''Fold:''' Likewise many other CBMs the CBM6 modules, roughly containing 120 amino acids, display the overall fold of a β-sandwich, predominantly consisting of five antiparallel β-strands on one face and four antiparallel β-strands on the other face, connected by loops with variable lengths. Within the hierarchal CATH classification the modules belong to the jelly-roll superfamily [http://www.cathdb.info/version/3.5/superfamily/2.60.120.260 2.60.120.260] called "galactose-binding domain-like" that contains 515 unique domains.
* '''Type:''' Due to the existance of the dual binding sites in CBM6s, both Type B and C binding properties have been observed for individual CBM6s.
* '''Features of ligand binding:''' The first identified ligand binding site was not, as usual, located at a shallow cleft on the concave surface of the β-sheets (binding site II, formerly called cleft B in CBM6). Alternatively, a binding site was found located at the apex, within the connecting loops of the two β-sheets (binding site I, formerly cleft A in CBM6) ([{{PDBlink}}1gmm PDB 1gmm]). Interestingly, some CBM6s display binding affinities for both binding sites ([{{PDBlink}}1uyy PDB 1uyy]), either with distinct specificities for each site ([{{PDBlink}}1uy0 PDB 1uy0] and [{{PDBlink}}1uyz PDB 1uyz]) or synergistic binding involving both sites at the same time <cite>Pires2004</cite>, while binding properties of other CBM6s make only use of one binding site, which is in general site I, at the apex (i.e. [{{PDBlink}}1uxx PDB 1uxx];[{{PDBlink}}1nae PDB 1nae];[{{PDBlink}}1w9w PDB 1w9w]). The apex site I is made up of two important, highly conserved aromatic residues (mostly W and Y) that "sandwich" a sugar monomer <cite>Czjzek2001;Abbott2009</cite>. These conserved residues are neighboured by a much more variable loop (defined as zone E in Abbott et al. <cite>Abbott2009</cite>) that make up the diversity in binding specificity. Consistantly, a variable number of sugar-binding subites have been observed for site I, ranging from one (end binder) up to five binding subsites. The precise structural and energetic contributions of four of the binding subsites have been dissected, for the first time, in detail by combining crystallography and ITC in the case of the ''Clostridium stercorarium ''CsCBM6-1 <cite>Lammerts2004</cite>. To date, only one CBM6 has been structuraly and biochemically characterized that makes use of binding site II, which is the CBM6 from ''Cellvibrio mixtus'' <cite>Henshaw2004;Pires2004</cite> ([{{PDBlink}}1uxz PDB 1uxz])

== Functionalities ==
''Content in this section should include, in paragraph form, a description of:''
* '''Functional role of CBM:''' The predominant functional role to date described for CBM6 modules is carbohydrate binding and targeting. It has been shown that this type of module synergistically enhances the activity of the adjacent catalytic domain on insoluble substrates.
* '''Most Common Associated Modules:''' 1. xylanases, lichenases, β-agarases, laminarinases; 2. dockerins, nodulation (NodB) and clotting factors.
* '''Novel Applications:''' The CBM6 from ''Clostridium thermocellum'' has been used to label plant tissues <cite>McCartney2004</cite>.

== Family Firsts ==
;First Identified
:The xylose binding CBM6 from a multi-modular xylanase/actetyl-esterase from ''Clostridium thermocellum'' (CtCBM6) was the first to be identified and biochemically characterized. To a lesser extent the module was also able to bind to avicel and acid-swollen cellulose <cite>Fernandes1999</cite>.
;First Structural Characterization
:The same xylose binding CBM6 from ''Clostridium thermocellum'' ([{{PDBlink}}1gmm PDB 1gmm]) was also the first structuraly characterized CBM6. The 3D structure revealed that the location of the ligand-binding site of carbohydrate-binding modules that have evolved from a common sequence was not conserved <cite>Czjzek2001</cite>.
== References ==
<biblio>
#Fernandes1999 pmid=10432306
#Czjzek2001 pmid=11673472
#Henshaw2004 pmid=15004011
#Pires2004 pmid=15010454
#Michel2009 pmid=19240276
#Takaki2002 pmid=11830593
#Abbott2009 pmid=19788273
#Lammerts2004 pmid=15223327
#McCartney2004 pmid=14769335

</biblio>

[[Category:Carbohydrate Binding Module Families|CBM006]]

Carbohydrate Binding Module Family 6

2014-01-05T15:03:30Z

Mirjam Czjzek:

{{UnderConstruction}}
* [[Author]]: ^^^Mirjam Czjzek^^^
* [[Responsible Curator]]: ^^^Mirjam Czjzek^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}CBM6.html
|}
</div>


== Ligand specificities ==
The ligand specificity of the first characterized CBM6, originating from a multimodular xylanase from ''Clostridium thermocellum'', was determined to be xylan <cite>Fernandes1999</cite>, although the results showed that this CBM6 was also able to bind to avicel and acid-swollen cellulose. This was also the first CBM6 for which a 3D structure was determined <cite>Czjzek2001</cite>, and multiple sequence alignments, analyzed in the light of the first 3D structure, already gave clear indications that large diversity in specificity was to be expected among CBM6 modules <cite>Czjzek2001</cite>. Remarkably, the characterization and 3D structure of a CBM6 from ''Cellvibrio mixtus'' revealed two distinct binding sites that displayed differential binding specificities <cite>Henshaw2004;Pires2004</cite>. CBM6 modules are in general attached to bacterial or archeal polysaccharide degrading enzymes and can be found attached to xylanases, cellulases, agarases, laminarinases, etc <cite>Michel2009</cite>. Interestingly, modules assigned to the CBM6 family have also been found associated to fungal enzymes and to the α-subunit of the coagulation factor G in horseshoe crabs [http://www.cazy.org/CBM6_eukaryota.html (see the eukarotic CBM6 occurence]). In the latter case, the β-1,3-glucan binding of the C-terminal tandem CBM6s has been demonstrated <cite>Takaki2002</cite>. Those CBM6s having characterized binding specificities cover : both linear and branched/decorated xylan, β-1,4-glucan (or cellulose), mixed-linked β-1,3-1,4-glucan (or lichenan), agarose, β-1,3-glucan (or laminarin) and chitin. Based on phylogenetic analyses of all reported CBM6 sequences in 2009 (a total of 167), four subfamilies have been defined that coincide with classes of substrate binding specificity as follows : subfamily 6a, hemicellulose; subfamily 6b, xylan; subfamily 6c, β-glucans with a variety of linkages; and subfamily 6d, agarose <cite>Abbott2009</cite>.

== Structural Features ==
''Content in this section should include, in paragraph form, a description of:''
* '''Fold:''' Likewise many other CBMs the CBM6 modules, roughly containing 120 amino acids, display the overall fold of a β-sandwich, predominantly consisting of five antiparallel β-strands on one face and four antiparallel β-strands on the other face, connected by loops with variable lengths. Within the hierarchal CATH classification the modules belong to the jelly-roll superfamily [http://www.cathdb.info/version/3.5/superfamily/2.60.120.260 2.60.120.260] called "galactose-binding domain-like" that contains 515 unique domains.
* '''Type:''' Due to the existance of the dual binding sites in CBM6s, both Type B and C binding properties have been observed for individual CBM6s.
* '''Features of ligand binding:''' The first identified ligand binding site was not, as usual, located at a shallow cleft on the concave surface of the β-sheets (binding site II, formerly called cleft B in CBM6). Alternatively, a binding site was found located at the apex, within the connecting loops of the two β-sheets (binding site I, formerly cleft A in CBM6) ([{{PDBlink}}1gmm PDB 1gmm]). Interestingly, some CBM6s display binding affinities for both binding sites ([{{PDBlink}}1uyy PDB 1uyy]), either with distinct specificities for each site ([{{PDBlink}}1uy0 PDB 1uy0] and [{{PDBlink}}1uyz PDB 1uyz]) or synergistic binding involving both sites at the same time <cite>Pires2004</cite>, while binding properties of other CBM6s make only use of one binding site, which is in general site I, at the apex (i.e. [{{PDBlink}}1uxx PDB 1uxx];[{{PDBlink}}1nae PDB 1nae];[{{PDBlink}}1w9w PDB 1w9w]). The apex site I is made up of two important, highly conserved aromatic residues (mostly W and Y) that "sandwich" a sugar monomer <cite>Czjzek2001;Abbott2009</cite>. These conserved residues are neighboured by a much more variable loop (defined as zone E in Abbott et al. <cite>Abbott2009</cite>) that make up the diversity in binding specificity. Consistantly, a variable number of sugar-binding subites have been observed for site I, ranging from one (end binder) up to five binding subsites. To date, only one CBM6 has been structuraly and biochemically characterized that makes use of binding site II, which is the CBM6 from ''Cellvibrio mixtus'' <cite>Henshaw2004;Pires2004</cite> ([{{PDBlink}}1uxz PDB 1uxz]).

== Functionalities ==
''Content in this section should include, in paragraph form, a description of:''
* '''Functional role of CBM:''' The predominant functional role to date described for CBM6 modules is carbohydrate binding and targeting. It has been shown that this type of module synergistically enhances the activity of the adjacent catalytic domain on insoluble substrates.
* '''Most Common Associated Modules:''' 1. xylanases, lichenases, β-agarases, laminarinases; 2. dockerins, nodulation (NodB) and clotting factors.
* '''Novel Applications:''' The CBM6 from ''Clostridium thermocellum'' has been used to label plant tissues <cite>McCartney2004</cite>.

== Family Firsts ==
;First Identified
:The xylose binding CBM6 from a multi-modular xylanase/actetyl-esterase from ''Clostridium thermocellum'' (CtCBM6) was the first to be identified and biochemically characterized. To a lesser extent the module was also able to bind to avicel and acid-swollen cellulose <cite>Fernandes1999</cite>.
;First Structural Characterization
:The same xylose binding CBM6 from ''Clostridium thermocellum'' ([{{PDBlink}}1gmm PDB 1gmm]) was also the first structuraly characterized CBM6. The 3D structure revealed that the location of the ligand-binding site of carbohydrate-binding modules that have evolved from a common sequence was not conserved <cite>Czjzek2001</cite>.
== References ==
<biblio>
#Fernandes1999 pmid=10432306
#Czjzek2001 pmid=11673472
#Henshaw2004 pmid=15004011
#Pires2004 pmid=15010454
#Michel2009 pmid=19240276
#Takaki2002 pmid=11830593
#Abbott2009 pmid=19788273
#McCartney2004 pmid=14769335

</biblio>

[[Category:Carbohydrate Binding Module Families|CBM006]]

Carbohydrate Binding Module Family 6

2014-01-05T15:01:07Z

Mirjam Czjzek:

{{UnderConstruction}}
* [[Author]]: ^^^Mirjam Czjzek^^^
* [[Responsible Curator]]: ^^^Mirjam Czjzek^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}CBM6.html
|}
</div>


== Ligand specificities ==
The ligand specificity of the first characterized CBM6, originating from a multimodular xylanase from ''Clostridium thermocellum'', was determined to be xylan <cite>Fernandes1999</cite>, although the results showed that this CBM6 was also able to bind to avicel and acid-swollen cellulose. This was also the first CBM6 for which a 3D structure was determined <cite>Czjzek2001</cite>, and multiple sequence alignments, analyzed in the light of the first 3D structure, already gave clear indications that large diversity in specificity was to be expected among CBM6 modules <cite>Czjzek2001</cite>. Remarkably, the characterization and 3D structure of a CBM6 from ''Cellvibrio mixtus'' revealed two distinct binding sites that displayed differential binding specificities <cite>Henshaw2004;Pires2004</cite>. CBM6 modules are in general attached to bacterial or archeal polysaccharide degrading enzymes and can be found attached to xylanases, cellulases, agarases, laminarinases, etc <cite>Michel2009</cite>. Interestingly, modules assigned to the CBM6 family have also been found associated to fungal enzymes and to the α-subunit of the coagulation factor G in horseshoe crabs [http://www.cazy.org/CBM6_eukaryota.html (see the eukarotic CBM6 occurence]). In the latter case, the β-1,3-glucan binding of the C-terminal tandem CBM6s has been demonstrated <cite>Takaki2002</cite>. Those CBM6s having characterized binding specificities cover : both linear and branched/decorated xylan, β-1,4-glucan (or cellulose), mixed-linked β-1,3-1,4-glucan (or lichenan), agarose, β-1,3-glucan (or laminarin) and chitin. Based on phylogenetic analyses of all reported CBM6 sequences in 2009 (a total of 167), four subfamilies have been defined that coincide with classes of substrate binding specificity as follows : subfamily 6a, hemicellulose; subfamily 6b, xylan; subfamily 6c, β-glucans with a variety of linkages; and subfamily 6d, agarose <cite>Abbott2009</cite>.

== Structural Features ==
''Content in this section should include, in paragraph form, a description of:''
* '''Fold:''' Likewise many other CBMs the CBM6 modules, roughly containing 120 amino acids, display the overall fold of a β-sandwich, predominantly consisting of five antiparallel β-strands on one face and four antiparallel β-strands on the other face, connected by loops with variable lengths. Within the hierarchal CATH classification the modules belong to the jelly-roll superfamily [http://www.cathdb.info/version/3.5/superfamily/2.60.120.260 2.60.120.260] called "galactose-binding domain-like" that contains 515 unique domains.
* '''Type:''' Due to the existance of the dual binding sites in CBM6s, both Type B and C binding properties have been observed for individual CBM6s.
* '''Features of ligand binding:''' The first identified ligand binding site was not, as usual, located at a shallow cleft on the concave surface of the β-sheets (binding site II, formerly called cleft B in CBM6). Alternatively, a binding site was found located at the apex, within the connecting loops of the two β-sheets (binding site I, formerly cleft A in CBM6) ([{{PDBlink}}1gmm PDB 1gmm]). Interestingly, some CBM6s display binding affinities for both binding sites ([{{PDBlink}}1uyy PDB 1uyy]), either with distinct specificities for each site ([{{PDBlink}}1uy0 PDB 1uy0] and [{{PDBlink}}1uyz PDB 1uyz]) or synergistic binding involving both sites at the same time <cite>Pires2004</cite>, while binding properties of other CBM6s make only use of one binding site, which is in general site I, at the apex (i.e. [{{PDBlink}}1uxx PDB 1uxx];[{{PDBlink}}1nae PDB 1nae];[{{PDBlink}}1w9w PDB 1w9w]). The apex site I is made up of two important, highly conserved aromatic residues (mostly W and Y) that "sandwich" a sugar monomer <cite>Czjzek2001;Abbott2009</cite>. These conserved residues are neighboured by a much more variable loop (defined as zone E in Abbott et al. <cite>Abbott2009</cite>) that make up the diversity in binding specificity. Consistantly, a variable number of sugar-binding subites have been observed for site I, ranging from one (end binder) up to five binding subsites. To date, only one CBM6 has been structuraly and biochemically characterized that makes use of binding site II, which is the CBM6 from ''Cellvibrio mixtus'' <cite>Henshaw2004;Pires2004</cite> ([{{PDBlink}}1uxz PDB 1uxz]).

== Functionalities ==
''Content in this section should include, in paragraph form, a description of:''
* '''Functional role of CBM:''' The predominant functional role to date described for CBM6 modules is carbohydrate binding and targeting. It has been shown that this type of module synergistically enhances the activity of the adjacent catalytic domain on insoluble substrates.
* '''Most Common Associated Modules:''' 1. xylanases, lichenases, β-agarases, laminarinases; 2. dockerins, nodulation (NodB) and clotting factors.
* '''Novel Applications:''' The CBM6 from 'Clostridium thermocellum'' has been used to label plant tissues <cite>McCartney2004</cite>.

== Family Firsts ==
;First Identified
:The xylose binding CBM6 from a multi-modular xylanase/actetyl-esterase from ''Clostridium thermocellum'' (CtCBM6) was the first to be identified and biochemically characterized. To a lesser extent the module was also able to bind to avicel and acid-swollen cellulose <cite>Fernandes1999</cite>.
;First Structural Characterization
:The same xylose binding CBM6 from ''Clostridium thermocellum'' ([{{PDBlink}}1gmm PDB 1gmm]) was also the first structuraly characterized CBM6. The 3D structure revealed that the location of the ligand-binding site of carbohydrate-binding modules that have evolved from a common sequence was not conserved <cite>Czjzek2001</cite>.
== References ==
<biblio>
#Fernandes1999 pmid=10432306
#Czjzek2001 pmid=11673472
#Henshaw2004 pmid=15004011
#Pires2004 pmid=15010454
#Michel2009 pmid=19240276
#Takaki2002 pmid=11830593
#Abbott2009 pmid=19788273
#McCartney2004 pmid=14769335

</biblio>

[[Category:Carbohydrate Binding Module Families|CBM006]]

Carbohydrate Binding Module Family 6

2014-01-05T14:06:34Z

Mirjam Czjzek:

{{UnderConstruction}}
* [[Author]]: ^^^Mirjam Czjzek^^^
* [[Responsible Curator]]: ^^^Mirjam Czjzek^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}CBM6.html
|}
</div>


== Ligand specificities ==
The ligand specificity of the first characterized CBM6, originating from a multimodular xylanase from ''Clostridium thermocellum'', was determined to be xylan <cite>Fernandes1999</cite>, although the results showed that this CBM6 was also able to bind to avicel and acid-swollen cellulose. This was also the first CBM6 for which a 3D structure was determined <cite>Czjzek2001</cite>, and multiple sequence alignments, analyzed in the light of the first 3D structure, already gave clear indications that large diversity in specificity was to be expected among CBM6 modules <cite>Czjzek2001</cite>. Remarkably, the characterization and 3D structure of a CBM6 from ''Cellvibrio mixtus'' revealed two distinct binding sites that displayed differential binding specificities <cite>Henshaw2004;Pires2004</cite>. CBM6 modules are in general attached to bacterial or archeal polysaccharide degrading enzymes and can be found attached to xylanases, cellulases, agarases, laminarinases, etc <cite>Michel2009</cite>. Interestingly, modules assigned to the CBM6 family have also been found associated to fungal enzymes and to the α-subunit of the coagulation factor G in horseshoe crabs [http://www.cazy.org/CBM6_eukaryota.html (see the eukarotic CBM6 occurence]). In the latter case, the β-1,3-glucan binding of the C-terminal tandem CBM6s has been demonstrated <cite>Takaki2002</cite>. Those CBM6s having characterized binding specificities cover : both linear and branched/decorated xylan, β-1,4-glucan (or cellulose), mixed-linked β-1,3-1,4-glucan (or lichenan), agarose, β-1,3-glucan (or laminarin) and chitin. Based on phylogenetic analyses of all reported CBM6 sequences in 2009 (a total of 167), four subfamilies have been defined that coincide with classes of substrate binding specificity as follows : subfamily 6a, hemicellulose; subfamily 6b, xylan; subfamily 6c, β-glucans with a variety of linkages; and subfamily 6d, agarose <cite>Abbott2009</cite>.

== Structural Features ==
''Content in this section should include, in paragraph form, a description of:''
* '''Fold:''' Likewise many other CBMs the CBM6 modules, roughly containing 120 amino acids, display the overall fold of a β-sandwich, predominantly consisting of five antiparallel β-strands on one face and four antiparallel β-strands on the other face, connected by loops with variable lengths. Within the hierarchal CATH classification the modules belong to the jelly-roll superfamily [http://www.cathdb.info/version/3.5/superfamily/2.60.120.260 2.60.120.260] called "galactose-binding domain-like" that contains 515 unique domains.
* '''Type:''' Due to the existance of the dual binding sites in CBM6s, both Type B and C binding properties have been observed for individual CBM6s.
* '''Features of ligand binding:''' The first identified ligand binding site was not, as usual, located at a shallow cleft on the concave surface of the β-sheets (binding site II, formerly called cleft B in CBM6). Alternatively, a binding site was found located at the apex, within the connecting loops of the two β-sheets (binding site I, formerly cleft A in CBM6) ([{{PDBlink}}1gmm PDB 1gmm]). Interestingly, some CBM6s display binding affinities for both binding sites ([{{PDBlink}}1uyy PDB 1uyy]), either with distinct specificities for each site ([{{PDBlink}}1uy0 PDB 1uy0] and [{{PDBlink}}1uyz PDB 1uyz]) or synergistic binding involving both sites at the same time <cite>Pires2004</cite>, while binding properties of other CBM6s make only use of one binding site, which is in general site I, at the apex (i.e. [{{PDBlink}}1uxx PDB 1uxx];[{{PDBlink}}1nae PDB 1nae];[{{PDBlink}}1w9w PDB 1w9w]). The apex site I is made up of two important, highly conserved aromatic residues (mostly W and Y) that "sandwich" a sugar monomer <cite>Czjzek2001;Abbott2009</cite>. These conserved residues are neighboured by a much more variable loop (defined as zone E in Abbott et al. <cite>Abbott2009</cite>) that make up the diversity in binding specificity. Consistantly, a variable number of sugar-binding subites have been observed for site I, ranging from one (end binder) up to five binding subsites. To date, only one CBM6 has been structuraly and biochemically characterized that makes use of binding site II, which is the CBM6 from ''Cellvibrio mixtus'' <cite>Henshaw2004;Pires2004</cite> ([{{PDBlink}}1uxz PDB 1uxz]).

== Functionalities ==
''Content in this section should include, in paragraph form, a description of:''
* '''Functional role of CBM:''' The predominant functional role to date described for CBM6 modules is carbohydrate binding and targeting. It has been shown that this type of module synergistically enhances the activity of the adjacent catalytic domain on insoluble substrates.
* '''Most Common Associated Modules:''' 1. xylanases, lichenases, β-agarases, laminarinases; 2. dockerins, nodulation factors and clotting factors.
* '''Novel Applications:''' Include here if CBM has been used to modify another enzyme, or if a CBM was used to label plant/mammalian tissues? Etc.

== Family Firsts ==
;First Identified
:The xylose binding CBM6 from a multi-modular xylanase/actetyl-esterase from ''Clostridium thermocellum'' (CtCBM6) was the first to be identified and biochemically characterized. To a lesser extent the module was also able to bind to avicel and acid-swollen cellulose <cite>Fernandes1999</cite>.
;First Structural Characterization
:The same xylose binding CBM6 from ''Clostridium thermocellum'' ([{{PDBlink}}1gmm PDB 1gmm]) was also the first structuraly characterized CBM6. The 3D structure revealed that the location of the ligand-binding site of carbohydrate-binding modules that have evolved from a common sequence was not conserved <cite>Czjzek2001</cite>.
== References ==
<biblio>
#Fernandes1999 pmid=10432306
#Czjzek2001 pmid=11673472
#Henshaw2004 pmid=15004011
#Pires2004 pmid=15010454
#Michel2009 pmid=19240276
#Takaki2002 pmid=11830593
#Abbott2009 pmid=19788273

</biblio>

[[Category:Carbohydrate Binding Module Families|CBM006]]

Carbohydrate Binding Module Family 6

2014-01-05T14:03:07Z

Mirjam Czjzek:

{{UnderConstruction}}
* [[Author]]: ^^^Mirjam Czjzek^^^
* [[Responsible Curator]]: ^^^Mirjam Czjzek^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}CBM6.html
|}
</div>


== Ligand specificities ==
The ligand specificity of the first characterized CBM6, originating from a multimodular xylanase from ''Clostridium thermocellum'', was determined to be xylan <cite>Fernandes1999</cite>, although the results showed that this CBM6 was also able to bind to Avicel and acid-swollen cellulose. This was also the first CBM6 for which a 3D structure was determined <cite>Czjzek2001</cite>, and multiple sequence alignments, analyzed in the light of the first 3D structure, already gave clear indications that large diversity in specificity was to be expected among CBM6 modules <cite>Czjzek2001</cite>. Remarkably, the characterization and 3D structure of a CBM6 from ''Cellvibrio mixtus'' revealed two distinct binding sites that displayed differential binding specificities <cite>Henshaw2004;Pires2004</cite>. CBM6 modules are in general attached to bacterial or archeal polysaccharide degrading enzymes and can be found attached to xylanases, cellulases, agarases, laminarinases, etc <cite>Michel2009</cite>. Interestingly, modules assigned to the CBM6 family have also been found associated to fungal enzymes and to the α-subunit of the coagulation factor G in horseshoe crabs [http://www.cazy.org/CBM6_eukaryota.html (see the eukarotic CBM6 occurence]). In the latter case, the β-1,3-glucan binding of the C-terminal tandem CBM6s has been demonstrated <cite>Takaki2002</cite>. Those CBM6s having characterized binding specificities cover : both linear and branched/decorated xylan, β-1,4-glucan (or cellulose), mixed-linked β-1,3-1,4-glucan (or lichenan), agarose, β-1,3-glucan (or laminarin) and chitin. Based on phylogenetic analyses of all reported CBM6 sequences in 2009 (a total of 167), four subfamilies have been defined that coincide with classes of substrate binding specificity as follows : subfamily 6a, hemicellulose; subfamily 6b, xylan; subfamily 6c, β-glucans with a variety of linkages; and subfamily 6d, agarose <cite>Abbott2009</cite>.

== Structural Features ==
''Content in this section should include, in paragraph form, a description of:''
* '''Fold:''' Likewise many other CBMs the CBM6 modules, roughly containing 120 amino acids, display the overall fold of a β-sandwich, predominantly consisting of five antiparallel β-strands on one face and four antiparallel β-strands on the other face, connected by loops with variable lengths. Within the hierarchal CATH classification the modules belong to the jelly-roll superfamily [http://www.cathdb.info/version/3.5/superfamily/2.60.120.260 2.60.120.260] called "galactose-binding domain-like" that contains 515 unique domains.
* '''Type:''' Due to the existance of the dual binding sites in CBM6s, both Type B and C binding properties have been observed for individual CBM6s.
* '''Features of ligand binding:''' The first identified ligand binding site was not, as usual, located at a shallow cleft on the concave surface of the β-sheets (binding site II, formerly called cleft B in CBM6). Alternatively, a binding site was found located at the apex, within the connecting loops of the two β-sheets (binding site I, formerly cleft A in CBM6) ([{{PDBlink}}1gmm PDB 1gmm]). Interestingly, some CBM6s display binding affinities for both binding sites ([{{PDBlink}}1uyy PDB 1uyy]), either with distinct specificities for each site ([{{PDBlink}}1uy0 PDB 1uy0] and [{{PDBlink}}1uyz PDB 1uyz]) or synergistic binding involving both sites at the same time <cite>Pires2004</cite>, while binding properties of other CBM6s make only use of one binding site, which is in general site I, at the apex (i.e. [{{PDBlink}}1uxx PDB 1uxx];[{{PDBlink}}1nae PDB 1nae];[{{PDBlink}}1w9w PDB 1w9w]). The apex site I is made up of two important, highly conserved aromatic residues (mostly W and Y) that "sandwich" a sugar monomer <cite>Czjzek2001;Abbott2009</cite>. These conserved residues are neighboured by a much more variable loop (defined as zone E in Abbott et al. <cite>Abbott2009</cite>) that make up the diversity in binding specificity. Consistantly, a variable number of sugar-binding subites have been observed for site I, ranging from one (end binder) up to five binding subsites. To date, only one CBM6 has been structuraly and biochemically characterized that makes use of binding site II, which is the CBM6 from ''Cellvibrio mixtus'' <cite>Henshaw2004;Pires2004</cite> ([{{PDBlink}}1uxz PDB 1uxz]).

== Functionalities ==
''Content in this section should include, in paragraph form, a description of:''
* '''Functional role of CBM:''' The predominant functional role to date described for CBM6 modules is carbohydrate binding and targeting. It has been shown that this type of module synergistically enhances the activity of the adjacent catalytic domain on insoluble substrates.
* '''Most Common Associated Modules:''' 1. xylanases, lichenases, β-agarases, laminarinases; 2. dockerins, nodulation factors and clotting factors.
* '''Novel Applications:''' Include here if CBM has been used to modify another enzyme, or if a CBM was used to label plant/mammalian tissues? Etc.

== Family Firsts ==
;First Identified
:The xylose binding CBM6 from a multi-modular xylanase/actetyl-esterase from ''Clostridium thermocellum'' (CtCBM6) was the first to be identified and biochemically characterized. To a lesser extent the module was also able to bind to Avicel and acid-swollen cellulose <cite>Fernandes1999</cite>.
;First Structural Characterization
:The same xylose binding CBM6 from ''Clostridium thermocellum'' ([{{PDBlink}}1gmm PDB 1gmm]) was also the first structuraly characterized CBM6. The 3D structure revealed that the location of the ligand-binding site of carbohydrate-binding modules that have evolved from a common sequence was not conserved <cite>Czjzek2001</cite>.
== References ==
<biblio>
#Fernandes1999 pmid=10432306
#Czjzek2001 pmid=11673472
#Henshaw2004 pmid=15004011
#Pires2004 pmid=15010454
#Michel2009 pmid=19240276
#Takaki2002 pmid=11830593
#Abbott2009 pmid=19788273

</biblio>

[[Category:Carbohydrate Binding Module Families|CBM006]]

Carbohydrate Binding Module Family 6

2014-01-05T14:00:22Z

Mirjam Czjzek:

{{UnderConstruction}}
* [[Author]]: ^^^Mirjam Czjzek^^^
* [[Responsible Curator]]: ^^^Mirjam Czjzek^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}CBM6.html
|}
</div>


== Ligand specificities ==
The ligand specificity of the first characterized CBM6, originating from a multimodular xylanase from ''Clostridium thermocellum'', was determined to be xylan <cite>Fernandes1999</cite>, although the results showed that this CBM6 was also able to bind to Avicel and acid-swollen cellulose. This was also the first CBM6 for which a 3D structure was determined <cite>Czjzek2001</cite>, and multiple sequence alignments, analyzed in the light of the first 3D structure, already gave clear indications that large diversity in specificity was to be expected among CBM6 modules <cite>Czjzek2001</cite>. Remarkably, the characterization and 3D structure of a CBM6 from ''Cellvibrio mixtus'' revealed two distinct binding sites that displayed differential binding specificities <cite>Henshaw2004;Pires2004</cite>. CBM6 modules are in general attached to bacterial or archeal polysaccharide degrading enzymes and can be found attached to xylanases, cellulases, agarases, laminarinases, etc <cite>Michel2009</cite>. Interestingly, modules assigned to the CBM6 family have also been found associated to fungal enzymes and to the α-subunit of the coagulation factor G in horseshoe crabs [http://www.cazy.org/CBM6_eukaryota.html (see the eukarotic CBM6 occurence]). In the latter case, the β-1,3-glucan binding of the C-terminal tandem CBM6s has been demonstrated <cite>Takaki2002</cite>. Those CBM6s having characterized binding specificities cover : both linear and branched/decorated xylan, β-1,4-glucan (or cellulose), mixed-linked β-1,3-1,4-glucan (or lichenan), agarose, β-1,3-glucan (or laminarin) and chitin. Based on phylogenetic analyses of all reported CBM6 sequences in 2009 (a total of 167), four subfamilies have been defined that coincide with classes of substrate binding specificity as follows : subfamily 6a, hemicellulose; subfamily 6b, xylan; subfamily 6c, β-glucans with a variety of linkages; and subfamily 6d, agarose <cite>Abbott2009</cite>.

== Structural Features ==
''Content in this section should include, in paragraph form, a description of:''
* '''Fold:''' Likewise many other CBMs the CBM6 modules, roughly containing 120 amino acids, display the overall fold of a β-sandwich, predominantly consisting of five antiparallel β-strands on one face and four antiparallel β-strands on the other face, connected by loops with variable lengths. Within the hierarchal CATH classification the modules belong to the jelly-roll superfamily [http://www.cathdb.info/version/3.5/superfamily/2.60.120.260 2.60.120.260] called the "galactose-binding domain-like" that contains 515 unique domains.
* '''Type:''' Due to the existance of the dual binding sites in CBM6s, both Type B and C binding properties have been observed for individual CBM6s.
* '''Features of ligand binding:''' The first identified ligand binding site was not, as usual, located at a shallow cleft on the concave surface of the β-sheets (binding site II, formerly called cleft B in CBM6). Alternatively, a binding site was found located at the apex, within the connecting loops of the two β-sheets (binding site I, formerly cleft A in CBM6) ([{{PDBlink}}1gmm PDB 1gmm]). Interestingly, some CBM6s display binding affinities for both binding sites ([{{PDBlink}}1uyy PDB 1uyy]), either with distinct specificities for each site ([{{PDBlink}}1uy0 PDB 1uy0] and [{{PDBlink}}1uyz PDB 1uyz]) or synergistic binding involving both sites at the same time <cite>Pires2004</cite>, while binding properties of other CBM6s make only use of one binding site, which is in general site I, at the apex (i.e. [{{PDBlink}}1uxx PDB 1uxx];[{{PDBlink}}1nae PDB 1nae];[{{PDBlink}}1w9w PDB 1w9w]). The apex site I is made up of two important, highly conserved aromatic residues (mostly W and Y) that "sandwich" a sugar monomer <cite>Czjzek2001;Abbott2009</cite>. These conserved residues are neighboured by a much more variable loop (defined as zone E in Abbott et al. <cite>Abbott2009</cite>) that make up the diversity in binding specificity. Consistantly, a variable number of sugar-binding subites have been observed for site I, ranging from one (end binder) up to five binding subsites. To date, only one CBM6 has been structuraly and biochemically characterized that makes use of binding site II, which is the CBM6 from ''Cellvibrio mixtus'' <cite>Henshaw2004;Pires2004</cite> ([{{PDBlink}}1uxz PDB 1uxz]).

== Functionalities ==
''Content in this section should include, in paragraph form, a description of:''
* '''Functional role of CBM:''' The predominant functional role to date described for CBM6 modules is carbohydrate binding and targeting. It has been shown that this type of module synergistically enhances the activity of the adjacent catalytic domain on insoluble substrates.
* '''Most Common Associated Modules:''' 1. xylanases, lichenases, β-agarases, laminarinases; 2. dockerins, nodulation factors and clotting factors.
* '''Novel Applications:''' Include here if CBM has been used to modify another enzyme, or if a CBM was used to label plant/mammalian tissues? Etc.

== Family Firsts ==
;First Identified
:The xylose binding CBM6 from a multi-modular xylanase/actetyl-esterase from ''Clostridium thermocellum'' (CtCBM6) was the first to be identified and biochemically characterized. To a lesser extent the module was also able to bind to Avicel and acid-swollen cellulose <cite>Fernandes1999</cite>.
;First Structural Characterization
:The same xylose binding CBM6 from ''Clostridium thermocellum'' (1GMM) was also the first structuraly characterized CBM6. The 3D structure revealed that the location of the ligand-binding site of carbohydrate-binding modules that have evolved from a common sequence was not conserved <cite>Czjzek2001</cite>.
== References ==
<biblio>
#Fernandes1999 pmid=10432306
#Czjzek2001 pmid=11673472
#Henshaw2004 pmid=15004011
#Pires2004 pmid=15010454
#Michel2009 pmid=19240276
#Takaki2002 pmid=11830593
#Abbott2009 pmid=19788273

</biblio>

[[Category:Carbohydrate Binding Module Families|CBM006]]

Carbohydrate Binding Module Family 6

2014-01-05T13:53:50Z

Mirjam Czjzek:

{{UnderConstruction}}
* [[Author]]: ^^^Mirjam Czjzek^^^
* [[Responsible Curator]]: ^^^Mirjam Czjzek^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}CBM6.html
|}
</div>


== Ligand specificities ==
The ligand specificity of the first characterized CBM6, originating from a multimodular xylanase from ''Clostridium thermocellum'', was determined to be xylan <cite>Fernandes1999</cite>, although the results showed that this CBM6 was also able to bind to Avicel and acid-swollen cellulose. This was also the first CBM6 for which a 3D structure was determined <cite>Czjzek2001</cite>, and multiple sequence alignments, analyzed in the light of the first 3D structure, already gave clear indications that large diversity in specificity was to be expected among CBM6 modules <cite>Czjzek2001</cite>. Remarkably, the characterization and 3D structure of a CBM6 from ''Cellvibrio mixtus'' revealed two distinct binding sites that displayed differential binding specificities <cite>Henshaw2004;Pires2004</cite>. CBM6 modules are in general attached to bacterial or archeal polysaccharide degrading enzymes and can be found attached to xylanases, cellulases, agarases, laminarinases, etc <cite>Michel2009</cite>. Interestingly, modules assigned to the CBM6 family have also been found associated to fungal enzymes and to the α-subunit of the coagulation factor G in horseshoe crabs [http://www.cazy.org/CBM6_eukaryota.html (see the eukarotic CBM6 occurence]). In the latter case, the β-1,3-glucan binding of the C-terminal tandem CBM6s has been demonstrated <cite>Takaki2002</cite>. Those CBM6s having characterized binding specificities cover : both linear and branched/decorated xylan, β-1,4-glucan (or cellulose), mixed-linked β-1,3-1,4-glucan (or lichenan), agarose, β-1,3-glucan (or laminarin) and chitin. Based on phylogenetic analyses of all reported CBM6 sequences in 2009 (a total of 167), four subfamilies have been defined that coincide with classes of substrate binding specificity as follows : subfamily 6a, hemicellulose; subfamily 6b, xylan; subfamily 6c, β-glucans with a variety of linkages; and subfamily 6d, agarose <cite>Abbott2009</cite>.

== Structural Features ==
''Content in this section should include, in paragraph form, a description of:''
* '''Fold:''' Likewise many other CBMs the CBM6 modules, roughly containing 120 amino acids, display the overall fold of a β-sandwich, predominantly consisting of five antiparallel β-strands on one face and four antiparallel β-strands on the other face, connected by loops with variable lengths. Within the hierarchal CATH classification the modules belong to the jelly-roll superfamily [http://www.cathdb.info/version/3.5/superfamily/2.60.120.260 2.60.120.260] called the "galactose-binding domain-like" that contains 515 unique domains.
* '''Type:''' Due to the existance of the dual binding sites in CBM6s, both Type B and C binding properties have been observed for individual CBM6s.
* '''Features of ligand binding:''' The first identified ligand binding site was not, as usual, located at a shallow cleft on the concave surface of the β-sheets (binding site II, formerly called cleft B in CBM6). Alternatively, a binding site was found located at the apex, within the connecting loops of the two β-sheets (binding site I, formerly cleft A in CBM6) ([{{PDBlink}}1gmm PDB 1gmm]). Interestingly, some CBM6s display binding affinities for both binding sites ([{{PDBlink}}1uyy PDB 1uyy]), either with distinct specificities for each site ([{{PDBlink}}1uy0 PDB 1uy0] and [{{PDBlink}}1uyz PDB 1uyz]) or synergistic binding involving both sites at the same time <cite>Pires2004</cite>, while binding properties of other CBM6s make only use of one binding site, which is in general site I, at the apex (i.e. [{{PDBlink}}1uxx PDB 1uxx];[{{PDBlink}}1nae PDB 1nae];[{{PDBlink}}1w9w PDB 1w9w]). The apex site I is made up of two important, highly conserved aromatic residues (mostly W and Y) that "sandwich" a sugar monomer <cite>Czjzek2001;Abbott2009</cite>. These conserved residues are neighboured by a much more variable loop (defined as zone E in Abbott et al. <cite>Abbott2009</cite>) that make up the diversity in binding specificity. Consistantly, a variable number of sugar-binding subites have been observed for site I, ranging from one (end binder) up to five binding subsites. To date, only one CBM6 has been structuraly and biochemically characterized that makes use of binding site II, which is the CBM6 from ''Cellvibrio mixtus'' <cite>Henshaw2004;Pires2004</cite> ([{{PDBlink}}1uxz PDB 1uxz]).

== Functionalities ==
''Content in this section should include, in paragraph form, a description of:''
* '''Functional role of CBM:''' Describe common functional roles such as targeting, disruptive, anchoring, proximity/position on substrate.
* '''Most Common Associated Modules:''' 1. Glycoside Hydrolase Activity; 2. Additional Associated Modules (other CBM, FNIII, cohesin, dockerins, expansins, etc.)
* '''Novel Applications:''' Include here if CBM has been used to modify another enzyme, or if a CBM was used to label plant/mammalian tissues? Etc.

== Family Firsts ==
;First Identified
:The xylose binding CBM6 from a multi-modular xylanase/actetyl-esterase from ''Clostridium thermocellum'' (CtCBM6) was the first to be identified and biochemically characterized. To a lesser extent the module was also able to bind to Avicel and acid-swollen cellulose <cite>Fernandes1999</cite>.
;First Structural Characterization
:The same xylose binding CBM6 from ''Clostridium thermocellum'' (1GMM) was also the first structuraly characterized CBM6. The 3D structure revealed that the location of the ligand-binding site of carbohydrate-binding
modules that have evolved from a common sequence was not conserved <cite>Czjzek2001</cite>.
== References ==
<biblio>
#Fernandes1999 pmid=10432306
#Czjzek2001 pmid=11673472
#Henshaw2004 pmid=15004011
#Pires2004 pmid=15010454
#Michel2009 pmid=19240276
#Takaki2002 pmid=11830593
#Abbott2009 pmid=19788273

</biblio>

[[Category:Carbohydrate Binding Module Families|CBM006]]

Carbohydrate Binding Module Family 6

2014-01-05T13:29:20Z

Mirjam Czjzek:

{{UnderConstruction}}
* [[Author]]: ^^^Mirjam Czjzek^^^
* [[Responsible Curator]]: ^^^Mirjam Czjzek^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}CBM6.html
|}
</div>


== Ligand specificities ==
The ligand specificity of the first characterized CBM6, originating from a multimodular xylanase from ''Clostridium thermocellum'', was determined to be xylan <cite>Fernandes1999</cite>, although the results showed that this CBM6 was also able to bind to Avicel and acid-swollen cellulose. This was also the first CBM6 for which a 3D structure was determined <cite>Czjzek2001</cite>, and multiple sequence alignments, analyzed in the light of the first 3D structure, already gave clear indications that large diversity in specificity was to be expected among CBM6 modules <cite>Czjzek2001</cite>. Remarkably, the characterization and 3D structure of a CBM6 from ''Cellvibrio mixtus'' revealed two distinct binding sites that displayed differential binding specificities <cite>Henshaw2004;Pires2004</cite>. CBM6 modules are in general attached to bacterial or archeal polysaccharide degrading enzymes and can be found attached to xylanases, cellulases, agarases, laminarinases, etc <cite>Michel2009</cite>. Interestingly, modules assigned to the CBM6 family have also been found associated to fungal enzymes and to the α-subunit of the coagulation factor G in horseshoe crabs [http://www.cazy.org/CBM6_eukaryota.html (see the eukarotic CBM6 occurence]). In the latter case, the β-1,3-glucan binding of the C-terminal tandem CBM6s has been demonstrated <cite>Takaki2002</cite>. Those CBM6s having characterized binding specificities cover : both linear and branched/decorated xylan, β-1,4-glucan (or cellulose), mixed-linked β-1,3-1,4-glucan (or lichenan), agarose, β-1,3-glucan (or laminarin) and chitin. Based on phylogenetic analyses of all reported CBM6 sequences in 2009 (a total of 167), four subfamilies have been defined that coincide with classes of substrate binding specificity as follows : subfamily 6a, hemicellulose; subfamily 6b, xylan; subfamily 6c, β-glucans with a variety of linkages; and subfamily 6d, agarose <cite>Abbott2009</cite>.

== Structural Features ==
''Content in this section should include, in paragraph form, a description of:''
* '''Fold:''' Likewise many other CBMs the CBM6 modules, roughly containing 120 amino acids, display the overall fold of a β-sandwich, predominantly consisting of five antiparallel β-strands on one face and four antiparallel β-strands on the other face, connected by loops with variable lengths. Within the hierarchal CATH classification the modules belong to the jelly-roll superfamily [http://www.cathdb.info/version/3.5/superfamily/2.60.120.260 2.60.120.260] called the "galactose-binding domain-like" that contains 515 unique domains.
* '''Type:''' Due to the existance of the dual binding sites in CBM6s, both Type B and C binding properties have been observed for individual CBM6s.
* '''Features of ligand binding:''' The first identified ligand binding site was not, as usual, located at a shallow cleft on the concave surface of the β-sheets (binding site II, formerly called cleft B in CBM6). Alternatively, a binding site was found located at the apex, within the connecting loops of the two β-sheets (binding site I, formerly cleft A in CBM6) ([{{PDBlink}}1gmm PDB 1gmm]). Interestingly, some CBM6s display binding affinities for both binding sites ([{{PDBlink}}1uyy PDB 1uyy]), either with distinct specificities for each site ([{{PDBlink}}1uy0 PDB 1uy0] and [{{PDBlink}}1uyz PDB 1uyz]) or synergistic binding involving both sites at the same time <cite>Pires2004</cite>, while binding properties of other CBM6s make only use of one binding site, which is in general site I, at the apex (i.e. [{{PDBlink}}1uxx PDB 1uxx];[{{PDBlink}}1nae PDB 1nae];[{{PDBlink}}1w9w PDB 1w9w]). The apex site I is made up of two important, highly conserved aromatic residues (mostly W and Y) that "sandwich" a sugar monomer <cite>Czjzek2001;Abbott2009</cite>. These conserved residues are neighboured by a much more variable loop (defined as zone E in Abbott et al. <cite>Abbott2009</cite>) that make up the diversity in binding specificity. Consistantly, a variable number of sugar-binding subites have been observed for site I, ranging from one (end binder) up to five binding subsites. To date, only one CBM6 has been structuraly and biochemically characterized that makes use of binding site II, which is the CBM6 from ''Cellvibrio mixtus'' <cite>Henshaw2004;Pires2004</cite> ([{{PDBlink}}1uxz PDB 1uxz]).

== Functionalities ==
''Content in this section should include, in paragraph form, a description of:''
* '''Functional role of CBM:''' Describe common functional roles such as targeting, disruptive, anchoring, proximity/position on substrate.
* '''Most Common Associated Modules:''' 1. Glycoside Hydrolase Activity; 2. Additional Associated Modules (other CBM, FNIII, cohesin, dockerins, expansins, etc.)
* '''Novel Applications:''' Include here if CBM has been used to modify another enzyme, or if a CBM was used to label plant/mammalian tissues? Etc.

== Family Firsts ==
;First Identified
:Insert archetype here, possibly including ''very brief'' synopsis.
;First Structural Characterization
:Insert archetype here, possibly including ''very brief'' synopsis.

== References ==
<biblio>
#Fernandes1999 pmid=10432306
#Czjzek2001 pmid=11673472
#Henshaw2004 pmid=15004011
#Pires2004 pmid=15010454
#Michel2009 pmid=19240276
#Takaki2002 pmid=11830593
#Abbott2009 pmid=19788273

</biblio>

[[Category:Carbohydrate Binding Module Families|CBM006]]

Carbohydrate Binding Module Family 6

2014-01-05T12:17:01Z

Mirjam Czjzek:

{{UnderConstruction}}
* [[Author]]: ^^^Mirjam Czjzek^^^
* [[Responsible Curator]]: ^^^Mirjam Czjzek^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}CBM6.html
|}
</div>


== Ligand specificities ==
The ligand specificity of the first characterized CBM6, originating from a multimodular xylanase from ''Clostridium thermocellum'', was determined to be xylan <cite>Fernandes1999</cite>, although the results showed that this CBM6 was also able to bind to Avicel and acid-swollen cellulose. This was also the first CBM6 for which a 3D structure was determined <cite>Czjzek2001</cite>, and multiple sequence alignments, analyzed in the light of the first 3D structure, already gave clear indications that large diversity in specificity was to be expected among CBM6 modules <cite>Czjzek2001</cite>. Remarkably, the characterization and 3D structure of a CBM6 from ''Cellvibrio mixtus'' revealed two distinct binding sites that displayed differential binding specificities <cite>Henshaw2004;Pires2004</cite>. CBM6 modules are in general attached to bacterial or archeal polysaccharide degrading enzymes and can be found attached to xylanases, cellulases, agarases, laminarinases, etc <cite>Michel2009</cite>. Interestingly, modules assigned to the CBM6 family have also been found associated to fungal enzymes and to the α-subunit of the coagulation factor G in horseshoe crabs [http://www.cazy.org/CBM6_eukaryota.html (see the eukarotic CBM6 occurence]). In the latter case, the β-1,3-glucan binding of the C-terminal tandem CBM6s has been demonstrated <cite>Takaki2002</cite>. Those CBM6s having characterized binding specificities cover : both linear and branched/decorated xylan, β-1,4-glucan (or cellulose), mixed-linked β-1,3-1,4-glucan (or lichenan), agarose, β-1,3-glucan (or laminarin) and chitin. Based on phylogenetic analyses of all reported CBM6 sequences in 2009 (a total of 167), four subfamilies have been defined that coincide with classes of substrate binding specificity as follows : subfamily 6a, hemicellulose; subfamily 6b, xylan; subfamily 6c, β-glucans with a variety of linkages; and subfamily 6d, agarose <cite>Abbott2009</cite>.

== Structural Features ==
''Content in this section should include, in paragraph form, a description of:''
* '''Fold:''' Likewise many other CBMs, the modules, roughly containing 120 amino acids, display the overall fold of a β-sandwich, predominantly consisting of five antiparallel β-strands on one face and four antiparallel β-strands on the other face, connected by loops with variable lengths. Within the hierarchal CATH classification the modules belong to the jelly-roll superfamily [http://www.cathdb.info/version/3.5/superfamily/2.60.120.260 2.60.120.260] called the "galactose-binding domain-like" that contains 515 unique domains.
* '''Type:''' Due to the existance of the dual binding sites in CBM6s, both Type B and C binding properties have been observed for individual CBM6s.
* '''Features of ligand binding:''' The first identified ligand binding site was not, as usual, located at a shallow cleft on the concave surface of the β-sheets (binding site II, formerly called cleft B in CBM6). Alternatively, a binding site was found located at the apex, within the connecting loops of the two β-sheets (binding site I, formerly cleft A in CBM6) ([{{PDBlink}}1gmm PDB 1gmm]). Interestingly, some CBM6s display binding affinities for both binding sites ([{{PDBlink}}1uyy PDB 1uyy]), either with distinct specificities for each site ([{{PDBlink}}1uy0 PDB 1uy0] and [{{PDBlink}}1uyz PDB 1uyz]) or synergistic binding involving both sites at the same time <cite>Pires2004</cite>, while binding properties of other CBM6s make only us of one binding site, which is in general site I, at the apex ([{{PDBlink}}1uxx PDB 1uxx]). The apex site I is made up of two important, highly conserved aromatic residues (mostly W and Y) that "sandwich" a sugar monomer <cite>Czjzek2001;Abbott2009</cite>. These conserved residues are neighboured by a much more variable loop (defined as zone E in Abbott et al. <cite>Abbott2009</cite>) that make up the diversity in binding specificity. Consistantly, a variable number of sugar-binding subites have been observed for site I, ranging from one (non-reducing end binder) up to five binding subsites.

== Functionalities ==
''Content in this section should include, in paragraph form, a description of:''
* '''Functional role of CBM:''' Describe common functional roles such as targeting, disruptive, anchoring, proximity/position on substrate.
* '''Most Common Associated Modules:''' 1. Glycoside Hydrolase Activity; 2. Additional Associated Modules (other CBM, FNIII, cohesin, dockerins, expansins, etc.)
* '''Novel Applications:''' Include here if CBM has been used to modify another enzyme, or if a CBM was used to label plant/mammalian tissues? Etc.

== Family Firsts ==
;First Identified
:Insert archetype here, possibly including ''very brief'' synopsis.
;First Structural Characterization
:Insert archetype here, possibly including ''very brief'' synopsis.

== References ==
<biblio>
#Fernandes1999 pmid=10432306
#Czjzek2001 pmid=11673472
#Henshaw2004 pmid=15004011
#Pires2004 pmid=15010454
#Michel2009 pmid=19240276
#Takaki2002 pmid=11830593
#Abbott2009 pmid=19788273

</biblio>

[[Category:Carbohydrate Binding Module Families|CBM006]]

Carbohydrate Binding Module Family 6

2014-01-05T11:47:14Z

Mirjam Czjzek:

{{UnderConstruction}}
* [[Author]]: ^^^Mirjam Czjzek^^^
* [[Responsible Curator]]: ^^^Mirjam Czjzek^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}CBM6.html
|}
</div>


== Ligand specificities ==
The ligand specificity of the first characterized CBM6, originating from a multimodular xylanase from ''Clostridium thermocellum'', was determined to be xylan <cite>Fernandes1999</cite>, although the results showed that this CBM6 was also able to bind to Avicel and acid-swollen cellulose. This was also the first CBM6 for which a 3D structure was determined <cite>Czjzek2001</cite>, and multiple sequence alignments, analyzed in the light of the first 3D structure, already gave clear indications that large diversity in specificity was to be expected among CBM6 modules <cite>Czjzek2001</cite>. Remarkably, the characterization and 3D structure of a CBM6 from ''Cellvibrio mixtus'' revealed two distinct binding sites that displayed differential binding specificities <cite>Henshaw2004;Pires2004</cite>. CBM6 modules are in general attached to bacterial or archeal polysaccharide degrading enzymes and can be found attached to xylanases, cellulases, agarases, laminarinases, etc <cite>Michel2009</cite>. Interestingly, modules assigned to the CBM6 family have also been found associated to fungal enzymes and to the α-subunit of the coagulation factor G in horseshoe crabs [http://www.cazy.org/CBM6_eukaryota.html (see the eukarotic CBM6 occurence]). In the latter case, the β-1,3-glucan binding of the C-terminal tandem CBM6s has been demonstrated <cite>Takaki2002</cite>. Those CBM6s having characterized binding specificities cover : both linear and branched/decorated xylan, β-1,4-glucan (or cellulose), mixed-linked β-1,3-1,4-glucan (or lichenan), agarose, β-1,3-glucan (or laminarin) and chitin. Based on phylogenetic analyses of all reported CBM6 sequences in 2009 (a total of 167), four subfamilies have been defined that coincide with classes of substrate binding specificity as follows : subfamily 6a, hemicellulose; subfamily 6b, xylan; subfamily 6c, β-glucans with a variety of linkages; and subfamily 6d, agarose <cite>Abbott2009</cite>.

== Structural Features ==
''Content in this section should include, in paragraph form, a description of:''
* '''Fold:''' Likewise many other CBMs, the modules, roughly containing 120 amino acids, display the overall fold of a β-sandwich, predominantly consisting of five antiparallel β-strands on one face and four antiparallel β-strands on the other face, connected by loops with variable lengths. Within the hierarchal CATH classification the modules belong to the jelly-roll superfamily [http://www.cathdb.info/version/3.5/superfamily/2.60.120.260 2.60.120.260] called the "galactose-binding domain-like" that contains 515 unique domains.
* '''Type:''' Due to the existance of the dual binding sites in CBM6s, both Type B and C binding properties have been observed for individual CBM6s.
* '''Features of ligand binding:''' The first identified ligand binding site was not, as usual, located at a shallow cleft on the concave surface of the β-sheets (binding site II, formerly called cleft B in CBM6). Alternatively, a binding site was found located at the apex, within the connecting loops of the two β-sheets (binding site I, formerly cleft A in CBM6) ([{{PDBlink}}1gmm PDB 1gmm]). Interestingly, some CBM6s display binding affinities for both binding sites , either with distinct specificities for each site or synergistic involving both at the same time, while binding properties of other CBM6s make only us of one binding site, which is in general site I, at the apex. The apex site I is made up of two important, highly conserved aromatic residues (mostly W and Y) that "sandwich" a sugar monomer <cite>Czjzek2001;Abbott2009</cite>. These conserved residues are neighboured by a much more variable loop (defined as zone E in Abbott et al. <cite>Abbott2009</cite>) that make up the diversity in binding specificity. Consistantly, a variable number of sugar-binding subites have been observed for site I, ranging from one (non-reducing end binder) up to five binding subsites. and Describe CBM binding pocket location (Side or apex) important residues for binding (W, Y, F, subsites), interact with reducing end, non-reducing end, planar surface or within polysaccharide chains. Include examples pdb codes. Metal ion dependent. Etc.

== Functionalities ==
''Content in this section should include, in paragraph form, a description of:''
* '''Functional role of CBM:''' Describe common functional roles such as targeting, disruptive, anchoring, proximity/position on substrate.
* '''Most Common Associated Modules:''' 1. Glycoside Hydrolase Activity; 2. Additional Associated Modules (other CBM, FNIII, cohesin, dockerins, expansins, etc.)
* '''Novel Applications:''' Include here if CBM has been used to modify another enzyme, or if a CBM was used to label plant/mammalian tissues? Etc.

== Family Firsts ==
;First Identified
:Insert archetype here, possibly including ''very brief'' synopsis.
;First Structural Characterization
:Insert archetype here, possibly including ''very brief'' synopsis.

== References ==
<biblio>
#Fernandes1999 pmid=10432306
#Czjzek2001 pmid=11673472
#Henshaw2004 pmid=15004011
#Pires2004 pmid=15010454
#Michel2009 pmid=19240276
#Takaki2002 pmid=11830593
#Abbott2009 pmid=19788273

</biblio>

[[Category:Carbohydrate Binding Module Families|CBM006]]

Carbohydrate Binding Module Family 6

2014-01-05T11:44:06Z

Mirjam Czjzek:

{{UnderConstruction}}
* [[Author]]: ^^^Mirjam Czjzek^^^
* [[Responsible Curator]]: ^^^Mirjam Czjzek^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}CBM6.html
|}
</div>


== Ligand specificities ==
The ligand specificity of the first characterized CBM6, originating from a multimodular xylanase from ''Clostridium thermocellum'', was determined to be xylan <cite>Fernandes1999</cite>, although the results showed that this CBM6 was also able to bind to Avicel and acid-swollen cellulose. This was also the first CBM6 for which a 3D structure was determined <cite>Czjzek2001</cite>, and multiple sequence alignments, analyzed in the light of the first 3D structure, already gave clear indications that large diversity in specificity was to be expected among CBM6 modules <cite>Czjzek2001</cite>. Remarkably, the characterization and 3D structure of a CBM6 from ''Cellvibrio mixtus'' revealed two distinct binding sites that displayed differential binding specificities <cite>Henshaw2004;Pires2004</cite>. CBM6 modules are in general attached to bacterial or archeal polysaccharide degrading enzymes and can be found attached to xylanases, cellulases, agarases, laminarinases, etc <cite>Michel2009</cite>. Interestingly, modules assigned to the CBM6 family have also been found associated to fungal enzymes and to the α-subunit of the coagulation factor G in horseshoe crabs [http://www.cazy.org/CBM6_eukaryota.html (see the eukarotic CBM6 occurence]). In the latter case, the β-1,3-glucan binding of the C-terminal tandem CBM6s has been demonstrated <cite>Takaki2002</cite>. Those CBM6s having characterized binding specificities cover : both linear and branched/decorated xylan, β-1,4-glucan (or cellulose), mixed-linked β-1,3-1,4-glucan (or lichenan), agarose, β-1,3-glucan (or laminarin) and chitin. Based on phylogenetic analyses of all reported CBM6 sequences in 2009 (a total of 167), four subfamilies have been defined that coincide with classes of substrate binding specificity as follows : subfamily 6a, hemicellulose; subfamily 6b, xylan; subfamily 6c, β-glucans with a variety of linkages; and subfamily 6d, agarose <cite>Abbott2009</cite>.

== Structural Features ==
''Content in this section should include, in paragraph form, a description of:''
* '''Fold:''' Likewise many other CBMs, the modules, roughly containing 120 amino acids, display the overall fold of a β-sandwich, predominantly consisting of five antiparallel β-strands on one face and four antiparallel β-strands on the other face, connected by loops with variable lengths. Within the hierarchal CATH classification the modules belong to the jelly-roll superfamily [http://www.cathdb.info/version/3.5/superfamily/2.60.120.260 2.60.120.260] called the "galactose-binding domain-like" that contains 515 unique domains.
* '''Type:''' Due to the existance of the dual binding sites in CBM6s, both Type B and C binding properties have been observed for individual CBM6s.
* '''Features of ligand binding:''' The first identified ligand binding site was not, as usual, located at a shallow cleft on the concave surface of the β-sheets (binding site II, formerly called cleft B in CBM6). Alternatively, a binding site was found located at the apex, within the connecting loops of the two β-sheets (binding site I, formerly cleft A in CBM6). Interestingly, some CBM6s display binding affinities for both binding sites , either with distinct specificities for each site or synergistic involving both at the same time, while binding properties of other CBM6s make only us of one binding site, which is in general site I, at the apex. The apex site I is made up of two important, highly conserved aromatic residues (mostly W and Y) that "sandwich" a sugar monomer <cite>Czjzek2001;Abbott2009</cite>. These conserved residues are neighboured by a much more variable loop (defined as zone E in Abbott et al. <cite>Abbott2009</cite>) that make up the diversity in binding specificity. Consistantly, a variable number of sugar-binding subites have been observed for site I, ranging from one (non-reducing end binder) up to five binding subsites. and Describe CBM binding pocket location (Side or apex) important residues for binding (W, Y, F, subsites), interact with reducing end, non-reducing end, planar surface or within polysaccharide chains. Include examples pdb codes. Metal ion dependent. Etc.

== Functionalities ==
''Content in this section should include, in paragraph form, a description of:''
* '''Functional role of CBM:''' Describe common functional roles such as targeting, disruptive, anchoring, proximity/position on substrate.
* '''Most Common Associated Modules:''' 1. Glycoside Hydrolase Activity; 2. Additional Associated Modules (other CBM, FNIII, cohesin, dockerins, expansins, etc.)
* '''Novel Applications:''' Include here if CBM has been used to modify another enzyme, or if a CBM was used to label plant/mammalian tissues? Etc.

== Family Firsts ==
;First Identified
:Insert archetype here, possibly including ''very brief'' synopsis.
;First Structural Characterization
:Insert archetype here, possibly including ''very brief'' synopsis.

== References ==
<biblio>
#Fernandes1999 pmid=10432306
#Czjzek2001 pmid=11673472
#Henshaw2004 pmid=15004011
#Pires2004 pmid=15010454
#Michel2009 pmid=19240276
#Takaki2002 pmid=11830593
#Abbott2009 pmid=19788273

</biblio>

[[Category:Carbohydrate Binding Module Families|CBM006]]

Carbohydrate Binding Module Family 6

2014-01-05T11:25:35Z

Mirjam Czjzek:

{{UnderConstruction}}
* [[Author]]: ^^^Mirjam Czjzek^^^
* [[Responsible Curator]]: ^^^Mirjam Czjzek^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}CBM6.html
|}
</div>


== Ligand specificities ==
The ligand specificity of the first characterized CBM6, originating from a multimodular xylanase from ''Clostridium thermocellum'', was determined to be xylan <cite>Fernandes1999</cite>, although the results showed that this CBM6 was also able to bind to Avicel and acid-swollen cellulose. This was also the first CBM6 for which a 3D structure was determined <cite>Czjzek2001</cite>, and multiple sequence alignments, analyzed in the light of the first 3D structure, already gave clear indications that large diversity in specificity was to be expected among CBM6 modules <cite>Czjzek2001</cite>. Remarkably, the characterization and 3D structure of a CBM6 from ''Cellvibrio mixtus'' revealed two distinct binding sites that displayed differential binding specificities <cite>Henshaw2004;Pires2004</cite>. CBM6 modules are in general attached to bacterial or archeal polysaccharide degrading enzymes and can be found attached to xylanases, cellulases, agarases, laminarinases, etc <cite>Michel2009</cite>. Interestingly, modules assigned to the CBM6 family have also been found associated to fungal enzymes and to the α-subunit of the coagulation factor G in horseshoe crabs [http://www.cazy.org/CBM6_eukaryota.html (see the eukarotic CBM6 occurence]). In the latter case, the β-1,3-glucan binding of the C-terminal tandem CBM6s has been demonstrated <cite>Takaki2002</cite>. Those CBM6s having characterized binding specificities cover : both linear and branched/decorated xylan, β-1,4-glucan (or cellulose), mixed-linked β-1,3-1,4-glucan (or lichenan), agarose, β-1,3-glucan (or laminarin) and chitin. Based on phylogenetic analyses of all reported CBM6 sequences in 2009 (a total of 167), four subfamilies have been defined that coincide with classes of substrate binding specificity as follows : subfamily 6a, hemicellulose; subfamily 6b, xylan; subfamily 6c, β-glucans with a variety of linkages; and subfamily 6d, agarose <cite>Abbott2009</cite>.

== Structural Features ==
''Content in this section should include, in paragraph form, a description of:''
* '''Fold:''' Likewise many other CBMs, the modules, roughly containing 120 amino acids, display the overall fold of a β-sandwich, predominantly consisting of five antiparallel β-strands on one face and four antiparallel β-strands on the other face, connected by loops with variable lengths. Within the hierarchal CATH classification the modules belong to the jelly-roll [http://www.cathdb.info/version/3.5/superfamily/2.60.120.260 superfamily 2.60.120.260] called the "galactose-binding domain-like" that contains 515 unique domains.
* '''Type:''' Due to the existance of the dual binding sites in CBM6s, both Type B and C binding properties have been observed for individual CBM6s.
* '''Features of ligand binding:''' The first identified ligand binding site was not, as usual, located at a shallow cleft on the concave surface of the β-sheets (binding site II, formerly called cleft B in CBM6). Alternatively, a binding site was found located at the apex, within the connecting loops of the two β-sheets (binding site I, formerly cleft A in CBM6). Interestingly, some CBM6s display binding affinities for both binding sites , either with distinct specificities for each site or synergistic involving both at the same time, while binding properties of other CBM6s make only us of one binding site, which is in general site I, at the apex. Describe CBM binding pocket location (Side or apex) important residues for binding (W, Y, F, subsites), interact with reducing end, non-reducing end, planar surface or within polysaccharide chains. Include examples pdb codes. Metal ion dependent. Etc.

== Functionalities ==
''Content in this section should include, in paragraph form, a description of:''
* '''Functional role of CBM:''' Describe common functional roles such as targeting, disruptive, anchoring, proximity/position on substrate.
* '''Most Common Associated Modules:''' 1. Glycoside Hydrolase Activity; 2. Additional Associated Modules (other CBM, FNIII, cohesin, dockerins, expansins, etc.)
* '''Novel Applications:''' Include here if CBM has been used to modify another enzyme, or if a CBM was used to label plant/mammalian tissues? Etc.

== Family Firsts ==
;First Identified
:Insert archetype here, possibly including ''very brief'' synopsis.
;First Structural Characterization
:Insert archetype here, possibly including ''very brief'' synopsis.

== References ==
<biblio>
#Fernandes1999 pmid=10432306
#Czjzek2001 pmid=11673472
#Henshaw2004 pmid=15004011
#Pires2004 pmid=15010454
#Michel2009 pmid=19240276
#Takaki2002 pmid=11830593
#Abbott2009 pmid=19788273

</biblio>

[[Category:Carbohydrate Binding Module Families|CBM006]]

Carbohydrate Binding Module Family 6

2014-01-05T11:24:19Z

Mirjam Czjzek:

{{UnderConstruction}}
* [[Author]]: ^^^Mirjam Czjzek^^^
* [[Responsible Curator]]: ^^^Mirjam Czjzek^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}CBM6.html
|}
</div>


== Ligand specificities ==
The ligand specificity of the first characterized CBM6, originating from a multimodular xylanase from ''Clostridium thermocellum'', was determined to be xylan <cite>Fernandes1999</cite>, although the results showed that this CBM6 was also able to bind to Avicel and acid-swollen cellulose. This was also the first CBM6 for which a 3D structure was determined <cite>Czjzek2001</cite>, and multiple sequence alignments, analyzed in the light of the first 3D structure, already gave clear indications that large diversity in specificity was to be expected among CBM6 modules <cite>Czjzek2001</cite>. Remarkably, the characterization and 3D structure of a CBM6 from ''Cellvibrio mixtus'' revealed two distinct binding sites that displayed differential binding specificities <cite>Henshaw2004;Pires2004</cite>. CBM6 modules are in general attached to bacterial or archeal polysaccharide degrading enzymes and can be found attached to xylanases, cellulases, agarases, laminarinases, etc <cite>Michel2009</cite>. Interestingly, modules assigned to the CBM6 family have also been found associated to fungal enzymes and to the α-subunit of the coagulation factor G in horseshoe crabs [http://www.cazy.org/CBM6_eukaryota.html (see the eukarotic CBM6 occurence]). In the latter case, the β-1,3-glucan binding of the C-terminal tandem CBM6s has been demonstrated <cite>Takaki2002</cite>. Those CBM6s having characterized binding specificities cover : both linear and branched/decorated xylan, β-1,4-glucan (or cellulose), mixed-linked β-1,3-1,4-glucan (or lichenan), agarose, β-1,3-glucan (or laminarin) and chitin. Based on phylogenetic analyses of all reported CBM6 sequences in 2009 (a total of 167), four subfamilies have been defined that coincide with classes of substrate binding specificity as follows : subfamily 6a, hemicellulose; subfamily 6b, xylan; subfamily 6c, β-glucans with a variety of linkages; and subfamily 6d, agarose <cite>Abbott2009</cite>.

== Structural Features ==
''Content in this section should include, in paragraph form, a description of:''
* '''Fold:''' Likewise many other CBMs, the modules, roughly containing 120 amino acids, display the overall fold of a β-sandwich, predominantly consisting of five antiparallel β-strands on one face and four antiparallel β-strands on the other face, connected by loops with variable lengths. Within the hierarchal CATH classification the modules belong to the jelly-roll superfamily 2.60.120.260 [http://www.cathdb.info/version/3.5/superfamily/2.60.120.260] called the "galactose-binding domain-like" that contains 515 unique domains.
* '''Type:''' Due to the existance of the dual binding sites in CBM6s, both Type B and C binding properties have been observed for individual CBM6s.
* '''Features of ligand binding:''' The first identified ligand binding site was not, as usual, located at a shallow cleft on the concave surface of the β-sheets (binding site II, formerly called cleft B in CBM6). Alternatively, a binding site was found located at the apex, within the connecting loops of the two β-sheets (binding site I, formerly cleft A in CBM6). Interestingly, some CBM6s display binding affinities for both binding sites , either with distinct specificities for each site or synergistic involving both at the same time, while binding properties of other CBM6s make only us of one binding site, which is in general site I, at the apex. Describe CBM binding pocket location (Side or apex) important residues for binding (W, Y, F, subsites), interact with reducing end, non-reducing end, planar surface or within polysaccharide chains. Include examples pdb codes. Metal ion dependent. Etc.

== Functionalities ==
''Content in this section should include, in paragraph form, a description of:''
* '''Functional role of CBM:''' Describe common functional roles such as targeting, disruptive, anchoring, proximity/position on substrate.
* '''Most Common Associated Modules:''' 1. Glycoside Hydrolase Activity; 2. Additional Associated Modules (other CBM, FNIII, cohesin, dockerins, expansins, etc.)
* '''Novel Applications:''' Include here if CBM has been used to modify another enzyme, or if a CBM was used to label plant/mammalian tissues? Etc.

== Family Firsts ==
;First Identified
:Insert archetype here, possibly including ''very brief'' synopsis.
;First Structural Characterization
:Insert archetype here, possibly including ''very brief'' synopsis.

== References ==
<biblio>
#Fernandes1999 pmid=10432306
#Czjzek2001 pmid=11673472
#Henshaw2004 pmid=15004011
#Pires2004 pmid=15010454
#Michel2009 pmid=19240276
#Takaki2002 pmid=11830593
#Abbott2009 pmid=19788273

</biblio>

[[Category:Carbohydrate Binding Module Families|CBM006]]

Carbohydrate Binding Module Family 6

2014-01-05T10:37:36Z

Mirjam Czjzek:

Carbohydrate Binding Module Family 6

2013-12-20T08:16:42Z

Mirjam Czjzek:

Carbohydrate Binding Module Family 6

2013-12-20T08:12:59Z

Mirjam Czjzek:

Carbohydrate Binding Module Family 6

2013-12-20T07:56:32Z

Mirjam Czjzek:

Carbohydrate Binding Module Family 6

2013-12-20T07:55:10Z

Mirjam Czjzek:

Carbohydrate Binding Module Family 6

2013-12-19T09:09:47Z

Mirjam Czjzek:

Glycoside Hydrolase Family 86

2013-12-18T17:22:08Z

Mirjam Czjzek:

{{CuratorApproved}}
* [[Author]]: ^^^Mirjam Czjzek^^^
* [[Responsible Curator]]: ^^^Mirjam Czjzek^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH86'''
|-
|'''Clan'''
|GH-A
|-
|'''Mechanism'''
|probably retaining
|-
|'''Active site residues'''
|inferred from clan GH-A as two Glu
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}GH86.html
|}
</div>


== Substrate specificities ==
[[Glycoside hydrolases]] of family 86 have first been identified to be β-agarases (EC [{{EClink}}3.2.1.81 3.2.1.81]) that cleave β-1,4 glycosidic bonds of agarose. Four agarolytic enzymes have been characterized: AgrA from ''Pseudoalteromonas atlantica'', AgaO from ''Microbulbifer thermotolerans JAMB-A94'', Aga86E from ''Saccharophagus degradans 2-40'' <cite>Belas1989,Ohta2004,Ekborg2006</cite> and more recently a GH86 β-agarase from a non marine ''Vibrio'' species (sp. OA-2007)<cite>Ariga2012</cite>. AgaO from ''M. thermotolerans'' was reported to be an endo-hydrolytic enzyme, releasing neoagaro-hexaose as main product <cite>Ohta2004</cite>, while the recombinant Aga86E from ''S. degradans'' released only neoagarobiose in an exo-acting manner <cite>Ekborg2006</cite>. In june 2012, a first GH86 enzyme was identified in the human gut Bacteroidetes ''B. plebeius'' that was active on porphyran, an agarocolloïd in which the 3,6-anhydro-L-galactose unit (LA) of neutral agarose is replaced by L-galactose-6-sulfate (L6S). The endo-acting enzyme, BpGH86A, is inactive on agarose and the main products released by cleavage of β-1,4 glycosidic bonds of porphyran, are tetrasaccharides having the sequence L6S-G-L6S-G∼ <cite>Hehemann2012</cite>.

== Kinetics and Mechanism ==
A potential retaining mechanism of this glycoside hydrolase family can be inferred from analogy to clan [{{CAZyDBlink}}Glycoside-Hydrolases.html GH-A enzymes], and is confirmed by structural analyses of a product complex showing an arrangement of the putative catalytic residues that is in agreement with the double displacement mechanism <cite>Hehemann2012</cite>. However, no mechanistic or kinetic analysis demonstrating the stereochemical outcome of the reaction have been reported for this family to date.

== Catalytic Residues ==
The catalytic residues can be inferred from the crystal structure and by analogy to clan GH-A enzymes as two glutamate residues, which are Glu152 (acid/base) and Glu279 (nucleophile) in BpGH86A from ''B. plebeius'' <cite>Hehemann2012</cite>.

== Three-dimensional structures ==
The first 3D structure was determined in 2012 by <cite>Hehemann2012</cite> et al. In agreement with distant sequence homology to clan [{{CAZyDBlink}}Glycoside-Hydrolases.html GH-A enzymes], the overall topology contains an N-terminal (β/α)<sub>8</sub> barrel. However the enzyme architecture is more complex and contains two additional Cterminal β-sandwich domains, which align via their convex faces to the exterior of the (β/α)<sub>8</sub> barrel and connect with two N-terminal β-strands that become part of these C-terminal β-sandwich domains.

== Family Firsts ==
;Identification of first family member: The first member of this family, AgrA, was identified in ''Pseudoalteromonas atlantica'' <cite>Belas1989</cite>.
;First stereochemistry determination: the retaining mechanism is inferred from the arrangement of the most probable catalytic residues in the crystal structure of a product complex <cite>Hehemann2012</cite>.
;First catalytic nucleophile identification: Glu279 in BpGH86A from ''B.plebeius''.
;First general acid/base residue identification: Glu152 in BpGH86A from ''B.plebeius''.
;First 3-D structure: The crystal structure of BpGH86A from ''B.plebeius'', ([{{PDBlink}}4aw7 PDB 4aw7]).

== References ==
<biblio>
#Belas1989 pmid=2914859
#Ohta2004 pmid=15490156
#Ekborg2006 pmid=16672483
#Hehemann2012 pmid=23150581
#Ariga2012 pmid=22814498
</biblio>

[[Category:Glycoside Hydrolase Families|GH086]]

Glycoside Hydrolase Family 86

2013-12-18T17:17:51Z

Mirjam Czjzek: /* Family Firsts */

{{CuratorApproved}}
* [[Author]]: ^^^Mirjam Czjzek^^^
* [[Responsible Curator]]: ^^^Mirjam Czjzek^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH86'''
|-
|'''Clan'''
|GH-A
|-
|'''Mechanism'''
|probably retaining
|-
|'''Active site residues'''
|inferred from clan GH-A as two Glu
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}GH86.html
|}
</div>


== Substrate specificities ==
[[Glycoside hydrolases]] of family 86 have first been identified to be β-agarases (EC [{{EClink}}3.2.1.81 3.2.1.81]) that cleave β-1,4 glycosidic bonds of agarose. Four agarolytic enzymes have been characterized: AgrA from ''Pseudoalteromonas atlantica'', AgaO from ''Microbulbifer thermotolerans JAMB-A94'', Aga86E from ''Saccharophagus degradans 2-40'' <cite>Belas1989,Ohta2004,Ekborg2006</cite> and more recently a GH86 β-agarase from a non marine ''Vibrio'' species (sp. OA-2007)<cite>Osamu2012</cite>. AgaO from ''M. thermotolerans'' was reported to be an endo-hydrolytic enzyme, releasing neoagaro-hexaose as main product <cite>Ohta2004</cite>, while the recombinant Aga86E from ''S. degradans'' released only neoagarobiose in an exo-acting manner <cite>Ekborg2006</cite>. In june 2012, a first GH86 enzyme was identified in the human gut Bacteroidetes ''B. plebeius'' that was active on porphyran, an agarocolloïd in which the 3,6-anhydro-L-galactose unit (LA) of neutral agarose is replaced by L-galactose-6-sulfate (L6S). The endo-acting enzyme, BpGH86A, is inactive on agarose and the main products released by cleavage of β-1,4 glycosidic bonds of porphyran, are tetrasaccharides having the sequence L6S-G-L6S-G∼ <cite>Hehemann2012</cite>.

== Kinetics and Mechanism ==
A potential retaining mechanism of this glycoside hydrolase family can be inferred from analogy to clan [{{CAZyDBlink}}Glycoside-Hydrolases.html GH-A enzymes], and is confirmed by structural analyses of a product complex showing an arrangement of the putative catalytic residues that is in agreement with the double displacement mechanism <cite>Hehemann2012</cite>. However, no mechanistic or kinetic analysis demonstrating the stereochemical outcome of the reaction have been reported for this family to date.

== Catalytic Residues ==
The catalytic residues can be inferred from the crystal structure and by analogy to clan GH-A enzymes as two glutamate residues, which are Glu152 (acid/base) and Glu279 (nucleophile) in BpGH86A from ''B. plebeius'' <cite>Hehemann2012</cite>.

== Three-dimensional structures ==
The first 3D structure was determined in 2012 by <cite>Hehemann2012</cite> et al. In agreement with distant sequence homology to clan [{{CAZyDBlink}}Glycoside-Hydrolases.html GH-A enzymes], the overall topology contains an N-terminal (β/α)<sub>8</sub> barrel. However the enzyme architecture is more complex and contains two additional Cterminal β-sandwich domains, which align via their convex faces to the exterior of the (β/α)<sub>8</sub> barrel and connect with two N-terminal β-strands that become part of these C-terminal β-sandwich domains.

== Family Firsts ==
;Identification of first family member: The first member of this family, AgrA, was identified in ''Pseudoalteromonas atlantica'' <cite>Belas1989</cite>.
;First stereochemistry determination: the retaining mechanism is inferred from the arrangement of the most probable catalytic residues in the crystal structure of a product complex <cite>Hehemann2012</cite>.
;First catalytic nucleophile identification: Glu279 in BpGH86A from ''B.plebeius''.
;First general acid/base residue identification: Glu152 in BpGH86A from ''B.plebeius''.
;First 3-D structure: The crystal structure of BpGH86A from ''B.plebeius'', ([{{PDBlink}}4aw7 PDB 4aw7]).

== References ==
<biblio>
#Belas1989 pmid=2914859
#Ohta2004 pmid=15490156
#Ekborg2006 pmid=16672483
#Hehemann2012 pmid=23150581

</biblio>

[[Category:Glycoside Hydrolase Families|GH086]]

Glycoside Hydrolase Family 86

2013-12-18T16:48:12Z

Mirjam Czjzek:

{{CuratorApproved}}
* [[Author]]: ^^^Mirjam Czjzek^^^
* [[Responsible Curator]]: ^^^Mirjam Czjzek^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH86'''
|-
|'''Clan'''
|GH-A
|-
|'''Mechanism'''
|probably retaining
|-
|'''Active site residues'''
|inferred from clan GH-A as two Glu
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}GH86.html
|}
</div>


== Substrate specificities ==
[[Glycoside hydrolases]] of family 86 have first been identified to be β-agarases (EC [{{EClink}}3.2.1.81 3.2.1.81]) that cleave β-1,4 glycosidic bonds of agarose. Four agarolytic enzymes have been characterized: AgrA from ''Pseudoalteromonas atlantica'', AgaO from ''Microbulbifer thermotolerans JAMB-A94'', Aga86E from ''Saccharophagus degradans 2-40'' <cite>Belas1989,Ohta2004,Ekborg2006</cite> and more recently a GH86 β-agarase from a non marine ''Vibrio'' species (sp. OA-2007)<cite>Osamu2012</cite>. AgaO from ''M. thermotolerans'' was reported to be an endo-hydrolytic enzyme, releasing neoagaro-hexaose as main product <cite>Ohta2004</cite>, while the recombinant Aga86E from ''S. degradans'' released only neoagarobiose in an exo-acting manner <cite>Ekborg2006</cite>. In june 2012, a first GH86 enzyme was identified in the human gut Bacteroidetes ''B. plebeius'' that was active on porphyran, an agarocolloïd in which the 3,6-anhydro-L-galactose unit (LA) of neutral agarose is replaced by L-galactose-6-sulfate (L6S). The endo-acting enzyme, BpGH86A, is inactive on agarose and the main products released by cleavage of β-1,4 glycosidic bonds of porphyran, are tetrasaccharides having the sequence L6S-G-L6S-G∼ <cite>Hehemann2012</cite>.

== Kinetics and Mechanism ==
A potential retaining mechanism of this glycoside hydrolase family can be inferred from analogy to clan [{{CAZyDBlink}}Glycoside-Hydrolases.html GH-A enzymes], and is confirmed by structural analyses of a product complex showing an arrangement of the putative catalytic residues that is in agreement with the double displacement mechanism <cite>Hehemann2012</cite>. However, no mechanistic or kinetic analysis demonstrating the stereochemical outcome of the reaction have been reported for this family to date.

== Catalytic Residues ==
The catalytic residues can be inferred from the crystal structure and by analogy to clan GH-A enzymes as two glutamate residues, which are Glu152 (acid/base) and Glu279 (nucleophile) in BpGH86A from ''B. plebeius'' <cite>Hehemann2012</cite>.

== Three-dimensional structures ==
The first 3D structure was determined in 2012 by <cite>Hehemann2012</cite> et al. In agreement with distant sequence homology to clan [{{CAZyDBlink}}Glycoside-Hydrolases.html GH-A enzymes], the overall topology contains an N-terminal (β/α)<sub>8</sub> barrel. However the enzyme architecture is more complex and contains two additional Cterminal β-sandwich domains, which align via their convex faces to the exterior of the (β/α)<sub>8</sub> barrel and connect with two N-terminal β-strands that become part of these C-terminal β-sandwich domains.

== Family Firsts ==
;Identification of first family member: The first member of this family, AgrA, was identified in ''Pseudoalteromonas atlantica'' <cite>Belas1989</cite>.
;First stereochemistry determination: the retaining mechanism is inferred from the arrangement of the most probable catalytic residues in the crystal structure of a product complex <cite>Hehemann2012</cite>.
;First catalytic nucleophile identification: Glu279 in BpGH86A from ''B.plebeius''.
;First general acid/base residue identification: Glu152 in BpGH86A from ''B.plebeius''.
;First 3-D structure: BpGH86A from ''B.plebeius'', 4AW7.

== References ==
<biblio>
#Belas1989 pmid=2914859
#Ohta2004 pmid=15490156
#Ekborg2006 pmid=16672483
#Hehemann2012 pmid=23150581

</biblio>

[[Category:Glycoside Hydrolase Families|GH086]]

Glycoside Hydrolase Family 86

2013-12-18T16:23:36Z

Mirjam Czjzek: /* Kinetics and Mechanism */

{{CuratorApproved}}
* [[Author]]: ^^^Mirjam Czjzek^^^
* [[Responsible Curator]]: ^^^Mirjam Czjzek^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH86'''
|-
|'''Clan'''
|GH-A
|-
|'''Mechanism'''
|probably retaining
|-
|'''Active site residues'''
|inferred from clan GH-A as two Glu
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}GH86.html
|}
</div>


== Substrate specificities ==
[[Glycoside hydrolases]] of family 86 have first been identified to be β-agarases (EC [{{EClink}}3.2.1.81 3.2.1.81]) that cleave β-1,4 glycosidic bonds of agarose. Four agarolytic enzymes have been characterized: AgrA from ''Pseudoalteromonas atlantica'', AgaO from ''Microbulbifer thermotolerans JAMB-A94'', Aga86E from ''Saccharophagus degradans 2-40'' <cite>Belas1989,Ohta2004,Ekborg2006</cite> and more recently a GH86 β-agarase from a non marine ''Vibrio'' species (sp. OA-2007)<cite>Osamu2012</cite>. AgaO from ''M. thermotolerans'' was reported to be an endo-hydrolytic enzyme, releasing neoagaro-hexaose as main product <cite>Ohta2004</cite>, while the recombinant Aga86E from ''S. degradans'' released only neoagarobiose in an exo-acting manner <cite>Ekborg2006</cite>. In june 2012, a first GH86 enzyme was identified in the human gut Bacteroidetes ''B. plebeius'' that was active on porphyran, an agarocolloïd in which the 3,6-anhydro-L-galactose unit (LA) of neutral agarose is replaced by L-galactose-6-sulfate (L6S). The main products released by the endo-acting enzyme that cleaves β-1,4 glycosidic bonds of porphyran, are tetrasaccharides having the sequence L6S-G-L6S-G∼ <cite>Hehemann2012</cite>.

== Kinetics and Mechanism ==
A potential retaining mechanism of this glycoside hydrolase family can be inferred from analogy to clan [{{CAZyDBlink}}Glycoside-Hydrolases.html GH-A enzymes] and is confirmed by structural analyses of a product complex that shows an arrangement of the putative catalytic residues in agreement with the double displacement mechanism . No mechanistic or kinetic analysis demonstrating the stereochemical outcome of the reaction have been reported for this family to date.

== Catalytic Residues ==
Actually, the catalytic residues can only be inferred from analogy to clan GH-A enzymes as two glutamate residues.

== Three-dimensional structures ==
No 3D structure is available to date.

== Family Firsts ==
;Identification of first family member: The first member of this family, AgrA, was identified in ''Pseudoalteromonas atlantica'' <cite>Belas1989</cite>.
;First stereochemistry determination: not determined yet.
;First catalytic nucleophile identification: not determined yet.
;First general acid/base residue identification: not determined yet.
;First 3-D structure: not determined yet.

== References ==
<biblio>
#Belas1989 pmid=2914859
#Ohta2004 pmid=15490156
#Ekborg2006 pmid=16672483
#Hehemann2012 pmid=23150581

</biblio>

[[Category:Glycoside Hydrolase Families|GH086]]

Glycoside Hydrolase Family 86

2013-12-18T16:20:11Z

Mirjam Czjzek: /* Substrate specificities */

Glycoside Hydrolase Family 86

2013-12-18T16:00:02Z

Mirjam Czjzek: /* References */

Glycoside Hydrolase Family 86

2013-12-18T15:58:01Z

Mirjam Czjzek: /* Substrate specificities */

Carbohydrate Binding Module Family 6

2013-12-17T17:16:58Z

Mirjam Czjzek:

Carbohydrate Binding Module Family 6

2013-12-17T16:12:44Z

Mirjam Czjzek:

Carbohydrate Binding Module Family 6

2013-12-17T15:18:30Z

Mirjam Czjzek:

Carbohydrate Binding Module Family 6

2013-12-17T15:07:21Z

Mirjam Czjzek:

Carbohydrate Binding Module Family 6

2013-12-17T15:05:48Z

Mirjam Czjzek:

Carbohydrate Binding Module Family 6

2013-12-16T17:08:06Z

Mirjam Czjzek:

Glycoside Hydrolase Family 117

2011-05-09T12:11:06Z

Mirjam Czjzek:

Glycoside Hydrolase Family 117

2011-05-06T07:13:09Z

Mirjam Czjzek:

Glycoside Hydrolase Family 117

2011-05-06T07:10:47Z

Mirjam Czjzek:

Glycoside Hydrolase Family 86

2010-11-19T13:32:21Z

Mirjam Czjzek: