Syn/anti lateral protonation

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• Author: ^^^Wim Nerinckx^^^
• Responsible Curator: ^^^Spencer Williams^^^

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Overview

This page will provide a table (and eventually a full lexicon article) on the spatial positioning of the catalytic general acid residue in the active sites of glycoside hydrolases. The table below updates those found in the seminal paper on this concept by Heightman and Vasella [1], and the more recent summary by Nerinckx et al. [2].

Table

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Family	Clan	Structure fold	Anomeric specificity	Mechanism	Syn/anti protonator	Example PDB ID	Enzyme	Organism	Ligand	General acid	Nucleophile or General base	Primary reference
GH1	A	(β/α)8	beta	retaining	anti	4pbg	6-phospho-beta-galactosidase	Lactococcus lactis	product	Glu160	Glu375	[3]
GH2	A	(β/α)8	beta	retaining	anti	1jz0	beta-galactosidase	Escherechia coli	2-F-galactosyl	Glu461	Glu537	[4]
GH3	none	(β/α)8	beta	retaining	anti	1iew	exo-1,3-1,4-glucanase	Hordeum vulgare	2-F-glucosyl	Glu491	Asp285	[5]
GH5	A	(β/α)8	beta	retaining	anti	1iew	endo-1,4-glucanase	Bacillus agaradhaerans	2-F-glucosyl	Glu129	Glu228	[6]
GH6	none	(β/α)8	beta	inverting	syn	1ocn	cellobiohydrolase	Humicola insolens	Glc-isofagomine	Asp226	debated	[7]
GH7	B	β-jelly roll	beta	retaining	syn	1ovw	endo-1,4-glucanase	Fusarium oxysporum	Michaelis thio-Glc5	Glu202	Glu197	[8]
GH8	M	(α/α)6	beta	inverting	anti	1kwf	endo-1,4-glucanase	Clostridium thermocellum	Michaelis	Glu95	Asp278	[9]
GH9	none	(α/α)6	beta	inverting	syn	3tf4, 4tf4	cellulase	Thermomonospora fusca	product	Glu424	Asp55, Asp58	[10]
GH10	A	(β/α)8	beta	retaining	anti	2xyl	xylanase B (Cex)	Cellulomonas fimi	Xyl-2-F-xylosyl	Glu127	Glu233	[11]
GH11	C	β-jelly roll	beta	retaining	syn	1bvv	xylanase	Bacillus circulans	Xyl-2-F-xylosyl	Glu172	Glu78	[12]
GH12	C	β-jelly roll	beta	retaining	syn	2nlr	endo-1,4-glucanase	Streptomyces lividans	Glc2-2-F-glucosyl	Glu203	Glu120	[13]
GH13	H	(β/α)8	alpha	retaining	anti	1ckx	beta-cyclodextrin glucanotransferase	Bacillus circulans	Michaelis	Glu257	Asp229	[14]
GH14	none	(β/α)8	alpha	inverting	syn	1b9z	beta-amylase	Bacillus cereus	product	Glu172	Glu367	[15]
GH15	L	(α/α)6	alpha	inverting	syn	1gah	glucoamylase	Aspergillus awamori	acarbose	Glu179	Glu400	[16]
GH16	B	β-jelly roll	beta	retaining	syn	1urx	beta-agarase A	Zobellia galactanivorans	product	Glu152	Glu147	[17]
GH18	K	(β/α)8	beta	retaining	anti	1ffr	chitinase A	Serratia marcescens	Michaelis (NAG)6	Glu315	internal	[18]
GH20	K	(β/α)8	beta	retaining	anti	1c7s	chitobiase	Serratia marcescens	Michaelis chitobiose	Glu540	internal	[19]
GH22	none	lysozyme type	beta	retaining	syn	1h6m	lysozyme C	Gallus gallus	Chit-2-F-chitosyl	Glu35	Asp52	[20]
GH23	none	lysozyme type	beta	inverting	syn	1lsp	lysozyme G	Cygnus atratus	Bulgecin A	Glu73	internal	[21]
GH24	I	α + β	beta	inverting	syn	148l	lysozyme E	Bacteriophage T4	chitobiosyl	Glu11	Glu26	[22]
GH26	A	(β/α)8	beta	retaining	anti	1gw1	mannanase A	Cellvibrio japonicus	(Man2)-2-F-mannosyl	Glu212	Glu320	[23]
GH27	D	(β/α)8	alpha	retaining	anti	1ktc	α-N-acetyl galactosaminidase	Gallus gallus	NAGal	Asp201	Asp410	[24]
GH29	none	(β/α)8	alpha	retaining	syn	1hl9	α-L-fucosidase	Thermotoga maritima	2-F-fucopyranosyl	Glu266	Asp224	[25]
GH31	D	(β/α)8	alpha	retaining	anti	1xsk	α-xylosidase	Escherechia coli	5-F-xylosyl	Asp482	Asp416	[26]
GH32	J	5-fold β-propeller	alpha	retaining	anti	2add	fructan β-(2,1)-fructosidase	Cichorium intybus	sucrose	Glu201	Asp22	[27]
GH33	E	6-fold β-propeller	alpha	retaining	anti	1s0k	trans-sialidase	Trypanosoma cruzi	2-F,3-F-sialosyl	Asp59	Tyr342	[28]
GH34	E	6-fold β-propeller	alpha	retaining	anti	2bat	neuraminidase	Influenza A virus	sialic acid	Asp151	Tyr406	[29]
GH37	G	(α/α)6	alpha	inverting	anti	2jf4	trehalase	Escherechia coli	validoxylamine	Asp312	Glu496	[30]
GH38	none	(β/α)7	alpha	retaining	anti	1qwn	α-mannosidase II	Drosophila melanogaster	5-F-β-L-gulosyl	Asp341	Asp204	[31]
GH39	A	(β/α)8	beta	retaining	anti	1uhv	β-xylosidase	Thermoanaerobacterium saccharolyticum	2-F-xylosyl	Glu160	Glu277	[32]
GH42	A	(β/α)8	beta	retaining	anti	1kwk	β-galactosidase	Thermus thermophylus A4	galactose	Glu141	Glu312	[33]
GH44	none	(β/α)8	beta	retaining	anti	2eqd	endoglucanase	Clostridium thermocellum	cellooctaose	Glu186	Glu359	[34]
GH45	none	six-stranded β-barrel	beta	inverting	syn	4eng	endo-1,4-glucanase	Humicola insolens	product	Asp121	Asp10	[35]
GH47	none	(α/α)7	alpha	inverting	anti	1x9d	α-mannosidase I	Homo sapiens	Michaelis	Asp463	Glu599	[36], [37]
GH51	A	(β/α)8	alpha	retaining	anti	1pz2	α-L-arabinofuranosidase	Geobacillus stearothermophilus	L-arabinofuranosyl	Glu175	Glu294	[38]
GH54	none	β-sandwich	alpha	retaining	anti	1wd4	α-L-arabinofuranosidase B	Aspergillus kawachii	L-arabinofuranose	Asp297	Glu221	[39]
GH56	none	(β/α)7	beta	retaining	anti	1fcv	hyaluronidase	Apis mellifera	(hyaluron.)4	Glu113	internal	[40]
GH57	none	(β/α)7	alpha	retaining	anti	1kly	glucanotransferase	Thermococcus litoralis	acarbose	Asp214	Glu123	[41]
GH67	none	(β/α)8	alpha	inverting	syn	1gql	α-glucuronidase	Cellvibrio japonicus Ueda107	glucuronic acid	Glu292	unknown	[42]
GH68	J	5-fold β-propeller	beta	retaining	anti	1pt2	levansucrase	Bacillus subtilis	sucrose	Glu342	Asp86	[43]
GH74	none	7-fold β-propeller	beta	inverting	syn	2ebs	cellobiohydrolase (OXG-RCBH)	Geotrichum sp. m128	xyloglucan heptasaccharide	Asp465	Asp35	[44]
GH77	H	(β/α)8	alpha	retaining	anti	1esw	amylomaltase	Thermus aquaticus	acarbose	Asp395	Asp293	[45]
GH90	none	(β)-helix	alpha	inverting	anti	1tyw	endo-α-L-1,3-rhamnosidase	Enterobacteris phage P22	epitope fragment	Asp395	Asp392	[46]
GH94	none	(α/α)6	beta	inverting	syn	1v7x	chitobiose phosphorylase	Vibrio proteolyticus	GlcNAc	Asp492	phosphate	[47]
GH95	none	(α/α)6	alpha	inverting	anti	2ead	α-1,2-L-fucosidase	Bifibacterium bifidum	substrate	Glu566	Asn423 Asp766	[48]
GH102	none	double-psi beta-barrel	beta	retaining	syn	2pi8	lytic transglycosylase A	Escherechia coli	chitohexaose	Asp308	none	[49]

References

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1. Heightman, T.D. and Vasella, A.T. (1999) Recent Insights into Inhibition, Structure, and Mechanism of Configuration-Retaining Glycosidases. Angewandte Chemie-International Edition 38(6), 750-770. Article online.

8. Sulzenbacher G, Driguez H, Henrissat B, Schülein M, and Davies GJ. (1996). Structure of the Fusarium oxysporum endoglucanase I with a nonhydrolyzable substrate analogue: substrate distortion gives rise to the preferred axial orientation for the leaving group. Biochemistry. 1996;35(48):15280-7. DOI:10.1021/bi961946h |
13. Sulzenbacher G, Mackenzie LF, Wilson KS, Withers SG, Dupont C, and Davies GJ. (1999). The crystal structure of a 2-fluorocellotriosyl complex of the Streptomyces lividans endoglucanase CelB2 at 1.2 A resolution. Biochemistry. 1999;38(15):4826-33. DOI:10.1021/bi982648i |
15. Mikami B, Adachi M, Kage T, Sarikaya E, Nanmori T, Shinke R, and Utsumi S. (1999). Structure of raw starch-digesting Bacillus cereus beta-amylase complexed with maltose. Biochemistry. 1999;38(22):7050-61. DOI:10.1021/bi9829377 |
17. Allouch J, Helbert W, Henrissat B, and Czjzek M. (2004). Parallel substrate binding sites in a beta-agarase suggest a novel mode of action on double-helical agarose. Structure. 2004;12(4):623-32. DOI:10.1016/j.str.2004.02.020 |
23. Ducros VM, Zechel DL, Murshudov GN, Gilbert HJ, Szabó L, Stoll D, Withers SG, and Davies GJ. (2002). Substrate distortion by a beta-mannanase: snapshots of the Michaelis and covalent-intermediate complexes suggest a B(2,5) conformation for the transition state. Angew Chem Int Ed Engl. 2002;41(15):2824-7. DOI:10.1002/1521-3773(20020802)41:15<2824::AID-ANIE2824>3.0.CO;2-G |
25. Sulzenbacher G, Bignon C, Nishimura T, Tarling CA, Withers SG, Henrissat B, and Bourne Y. (2004). Crystal structure of Thermotoga maritima alpha-L-fucosidase. Insights into the catalytic mechanism and the molecular basis for fucosidosis. J Biol Chem. 2004;279(13):13119-28. DOI:10.1074/jbc.M313783200 |
33. Hidaka M, Fushinobu S, Ohtsu N, Motoshima H, Matsuzawa H, Shoun H, and Wakagi T. (2002). Trimeric crystal structure of the glycoside hydrolase family 42 beta-galactosidase from Thermus thermophilus A4 and the structure of its complex with galactose. J Mol Biol. 2002;322(1):79-91. DOI:10.1016/s0022-2836(02)00746-5 |
45. Przylas I, Terada Y, Fujii K, Takaha T, Saenger W, and Sträter N. (2000). X-ray structure of acarbose bound to amylomaltase from Thermus aquaticus. Implications for the synthesis of large cyclic glucans. Eur J Biochem. 2000;267(23):6903-13. DOI:10.1046/j.1432-1033.2000.01790.x |