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	Reference
GH1	A	(β/α)8	beta	retaining	anti	2cer	β-glycosidase S	Sulfolobus solfataricus P2	phenethyl glucoimidazol	Glu206	Glu387	[3]
GH2	A	(β/α)8	beta	retaining	anti	2vzu	exo-β-glucosaminidase	Amicolatopsis orientalis	PNP-β-d-glucosamine	Glu469	Glu541	[4]
GH3	none	(β/α)8	beta	retaining	anti	1iex	exo-1,3-1,4-glucanase	Hordeum vulgare	thiocellobiose	Glu491	Asp285	[5]
GH5	A	(β/α)8	beta	retaining	anti	1h2j	endo-β-1,4-glucanase	Bacillus agaradhaerens	2,4-DNP-2-F-cellobioside	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	thio-Glc5	Glu202	Glu197	[8]
GH8	M	(α/α)6	beta	inverting	anti	1kwf	endo-1,4-glucanase	Clostridium thermocellum	cellopentaose	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	1cxk	β-cyclodextrin glucanotransferase	Bacillus circulans	maltononaose	Glu257	Asp229	[14]
GH14	none	(β/α)8	alpha	inverting	syn	1b9z	β-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	β-agarase A	Zobellia galactanivorans	product	Glu152	Glu147	[17]
GH17	A	(β/α)8	beta	retaining	predicted anti by clan	see e.g. at GH1
GH18	K	(β/α)8	beta	retaining	anti	1ffr	chitinase A	Serratia marcescens	(NAG)6	Glu315	internal	[18]
GH20	K	(β/α)8	beta	retaining	anti	1c7s	chitobiase	Serratia marcescens	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-fuco- pyranosyl	Glu266	Asp224	[25]
GH30	A	(β/α)8	beta	retaining	predicted anti by clan	see e.g. at GH1
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]
GH35	A	(β/α)8	beta	retaining	predicted anti by clan	see e.g. at GH1
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	d-galactose	Glu141	Glu312	[33]
GH44	none	(β/α)8	beta	retaining	anti	2eqd	endoglucanase	Clostridium thermocellum	cellooctaose	Glu186	Glu359	[34]
GH45	none	6-strand. β-barrel	beta	inverting	syn	4eng	endo-1,4-glucanase	Humicola insolens	product	Asp121	Asp10	[35]
GH46	I	α + β	beta	inverting	predicted syn by clan	see at GH24
GH47	none	(α/α)7	alpha	inverting	anti	1x9d	α-mannosidase I	Homo sapiens	Michaelis	Asp463	Glu599	[36], [37]
GH48	M	(α/α)6	beta	inverting	predicted anti by clan	see at GH8
GH50	A	(β/α)8	beta	retaining	predicted anti by clan	see e.g. at GH1
GH51	A	(β/α)8	alpha	retaining	anti	1pz2	α-l-arabino- furanosidase	Geobacillus stearothermophilus	l-arabino- furanosyl	Glu175	Glu294	[38]
GH53	A	(β/α)8	beta	retaining	predicted anti by clan	see e.g. at GH1
GH54	none	β-sandwich	alpha	retaining	anti	1wd4	α-l-arabino- furanosidase B	Aspergillus kawachii	l-arabino- furanose	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]
GH59	A	(β/α)8	beta	retaining	predicted anti by clan	see e.g. at GH1
GH63	G	(α/α)6	alpha	inverting	predicted anti by clan	see at GH37
GH65	L	(α/α)6	alpha	inverting	predicted syn by clan	see at GH15
GH67	none	(β/α)8	alpha	inverting	syn	1gql	α-glucuronidase	Cellvibrio japonicus Ueda107	d-glucuronic acid	Glu292	unknown	[42]
GH68	J	5-fold β-propeller	beta	retaining	anti	1pt2	levansucrase	Bacillus subtilis	sucrose	Glu342	Asp86	[43]
GH70	H	(β/α)8	alpha	retaining	predicted anti by clan	see e.g. at GH13
GH72	A	(β/α)8	beta	retaining	predicted anti by clan	see e.g. at GH1
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]
GH79	A	(β/α)8	beta	retaining	predicted anti by clan	see e.g. at GH1
GH80	I	α + β	beta	inverting	predicted syn by clan	see at GH24
GH83	E	6-fold β-propeller	alpha	retaining	predicted anti by clan	see e.g. at GH33
GH85	K	(β/α)8	beta	retaining	predicted anti by clan	see e.g. at GH18
GH86	A	(β/α)8	beta	retaining	predicted anti by clan	see e.g. at GH1
GH89	none	(β/α)8	alpha	retaining	anti	2vcb	α-N-acetyl- glucosaminidase	Clostridium perfringens	PUGNAc	Glu483	Glu601	[46]
GH92	none	(α/α)6 + β-sandw.	alpha	inverting	anti	2ww1	α-1,2-mannosidase	Bacteroides thetaiota- omicron VPI-5482	thiomannobioside	Glu533	Asp644 Asp642	[47]
GH93	E	6-fold β-propeller	alpha	retaining	predicted anti by clan	see e.g. at GH33
GH94	none	(α/α)6	beta	inverting	syn	1v7x	chitobiose phosphorylase	Vibrio proteolyticus	GlcNAc	Asp492	phosphate	[48]
GH95	none	(α/α)6	alpha	inverting	anti	2ead	α-1,2-l-fucosidase	Bifidobacterium bifidum	substrate	Glu566	Asn423 Asp766	[49]
GH102	none	double-ψ β-barrel	beta	retaining	syn	2pi8	lytic transglycosylase A	Escherechia coli	chitohexaose	Asp308	none	[50]
GH113	A	(β/α)8	beta	retaining	predicted anti by clan	see e.g. at GH1

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.

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 |
31. Numao S, Kuntz DA, Withers SG, and Rose DR. (2003). Insights into the mechanism of Drosophila melanogaster Golgi alpha-mannosidase II through the structural analysis of covalent reaction intermediates. J Biol Chem. 2003;278(48):48074-83. DOI:10.1074/jbc.M309249200 |
36. Karaveg K, Siriwardena A, Tempel W, Liu ZJ, Glushka J, Wang BC, and Moremen KW. (2005). Mechanism of class 1 (glycosylhydrolase family 47) {alpha}-mannosidases involved in N-glycan processing and endoplasmic reticulum quality control. J Biol Chem. 2005;280(16):16197-207. DOI:10.1074/jbc.M500119200 |
37. Cantú D, Nerinckx W, and Reilly PJ. (2008). Theory and computation show that Asp463 is the catalytic proton donor in human endoplasmic reticulum alpha-(1-->2)-mannosidase I. Carbohydr Res. 2008;343(13):2235-42. DOI:10.1016/j.carres.2008.05.026 |
41. Imamura H, Fushinobu S, Yamamoto M, Kumasaka T, Jeon BS, Wakagi T, and Matsuzawa H. (2003). Crystal structures of 4-alpha-glucanotransferase from Thermococcus litoralis and its complex with an inhibitor. J Biol Chem. 2003;278(21):19378-86. DOI:10.1074/jbc.M213134200 |

47. Zhu et al. (2010) Nature Chemical Biology in the press; DOI: 10.1038/nchembio.278 direct link.