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	1h2j	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]
GH33	E	6-fold β-propeller	alpha	retaining	anti	1s0k	trans-sialidase	Trypanosoma cruzi	2-F,3-F-sialosyl	Asp59	Tyr342	[27]

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.

2. Nerinckx W, Desmet T, Piens K, and Claeyssens M. (2005). An elaboration on the syn-anti proton donor concept of glycoside hydrolases: electrostatic stabilisation of the transition state as a general strategy. FEBS Lett. 2005;579(2):302-12. DOI:10.1016/j.febslet.2004.12.021 |
3. Wiesmann C, Hengstenberg W, and Schulz GE. (1997). Crystal structures and mechanism of 6-phospho-beta-galactosidase from Lactococcus lactis. J Mol Biol. 1997;269(5):851-60. DOI:10.1006/jmbi.1997.1084 |
4. Juers DH, Heightman TD, Vasella A, McCarter JD, Mackenzie L, Withers SG, and Matthews BW. (2001). A structural view of the action of Escherichia coli (lacZ) beta-galactosidase. Biochemistry. 2001;40(49):14781-94. DOI:10.1021/bi011727i |
5. Hrmova M, Varghese JN, De Gori R, Smith BJ, Driguez H, and Fincher GB. (2001). Catalytic mechanisms and reaction intermediates along the hydrolytic pathway of a plant beta-D-glucan glucohydrolase. Structure. 2001;9(11):1005-16. DOI:10.1016/s0969-2126(01)00673-6 |
6. Varrot A and Davies GJ. (2003). Direct experimental observation of the hydrogen-bonding network of a glycosidase along its reaction coordinate revealed by atomic resolution analyses of endoglucanase Cel5A. Acta Crystallogr D Biol Crystallogr. 2003;59(Pt 3):447-52. DOI:10.1107/s0907444902023405 |
7. Varrot A, Macdonald J, Stick RV, Pell G, Gilbert HJ, and Davies GJ. (2003). Distortion of a cellobio-derived isofagomine highlights the potential conformational itinerary of inverting beta-glucosidases. Chem Commun (Camb). 2003(8):946-7. DOI:10.1039/b301592k |
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 |
9. Guérin DM, Lascombe MB, Costabel M, Souchon H, Lamzin V, Béguin P, and Alzari PM. (2002). Atomic (0.94 A) resolution structure of an inverting glycosidase in complex with substrate. J Mol Biol. 2002;316(5):1061-9. DOI:10.1006/jmbi.2001.5404 |
10. Irwin D, Shin DH, Zhang S, Barr BK, Sakon J, Karplus PA, and Wilson DB. (1998). Roles of the catalytic domain and two cellulose binding domains of Thermomonospora fusca E4 in cellulose hydrolysis. J Bacteriol. 1998;180(7):1709-14. DOI:10.1128/JB.180.7.1709-1714.1998 |
14. Uitdehaag JC, Mosi R, Kalk KH, van der Veen BA, Dijkhuizen L, Withers SG, and Dijkstra BW. (1999). X-ray structures along the reaction pathway of cyclodextrin glycosyltransferase elucidate catalysis in the alpha-amylase family. Nat Struct Biol. 1999;6(5):432-6. DOI:10.1038/8235 |
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 |