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

This table can be re-sorted by clicking on the icons in the header (javascript must be turned on in your browser). To reset the page to be sorted by GH family, click the page tab above the page title.

Family	Clan	Structure fold	Anomeric specificity	Mechanism	Example PDB ID	General acid	syn/anti	Nucleophile or General base	Ligand	Organism	Enzyme	Primary reference
GH1	A	(β/α)8	beta	retaining	4pbg	Glu160	anti	Glu375	product	Lactococcus lactis	6-phospho-beta-galactosidase	[3]
GH2	A	(β/α)8	beta	retaining	1jz0	Glu461	anti	Glu537	2-F-galactosyl	Escherechia coli	beta-galactosidase	[4]
GH3	none	(β/α)8	beta	retaining	1iew	Glu491	anti	Asp285	2-F-glucosyl	Hordeum vulgare	exo-1,3-1,4-glucanase	[5]
GH5	A	(β/α)8	beta	retaining	1h2j	Glu129	anti	Glu228	2-F-glucosyl	Bacillus agaradhaerans	endo-1,4-glucanase	[6]
GH6	none	(β/α)8	beta	inverting	1ocn	Asp226	syn	debated	Glc-isofagomine	Humicola insolens	cellobiohydrolase	[7]
GH7	B	β-jelly roll	beta	retaining	1ovw	Glu202	syn	Glu197	thio-Glc5	Fusarium oxysporum	endo-1,4-glucanase	[8]
GH8	M	(α/α)6	beta	inverting	1kwf	Glu95	anti	Asp278	Michaelis	Clostridium thermocellum	endo-1,4-glucanase	[9]
GH9	none	(α/α)6	beta	inverting	3tf4,4tf4	Glu424	syn	Asp55,Asp58	product	Thermomonospora fusca	cellulase	[10]
GH10	A	(β/α)8	beta	retaining	2xyl	Glu127	anti	Glu233	Xyl-2-F-xylosyl	Cellulomonas fimi	xylanase B (Cex)	[11]
GH11	C	β-jelly roll	beta	retaining	1bvv	Glu172	syn	Glu78	Xyl-2-F-xylosyl	Bacillus circulans	xylanase	[12]
GH12	C	β-jelly roll	beta	retaining	2nlr	Glu203	syn	Glu120	Glc2-2-F-glucosyl	Streptomyces lividans	endo-1,4-glucanase	[13]
GH13	H	(β/α)8	alpha	retaining	1ckx	Glu257	anti	Asp229	Michaelis	Bacillus circulans	beta-cyclodextrin glucanotransferase	[14]
GH14	none	(β/α)8	alpha	inverting	1b9z	Glu172	syn	Glu367	product	Bacillus cereus	beta-amylase	[15]
GH15	L	(α/α)6	alpha	inverting	1gah	Glu179	syn	Glu400	acarbose	Aspergillus awamori	glucoamylase	[16]
GH16	B	β-jelly roll	beta	retaining	1urx	Glu152	syn	Glu147	product	Zobellia galactanivorans	beta-agarase A	[17]

References

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 |
11. Notenboom V, Birsan C, Warren RA, Withers SG, and Rose DR. (1998). Exploring the cellulose/xylan specificity of the beta-1,4-glycanase cex from Cellulomonas fimi through crystallography and mutation. Biochemistry. 1998;37(14):4751-8. DOI:10.1021/bi9729211 |
12. Sidhu G, Withers SG, Nguyen NT, McIntosh LP, Ziser L, and Brayer GD. (1999). Sugar ring distortion in the glycosyl-enzyme intermediate of a family G/11 xylanase. Biochemistry. 1999;38(17):5346-54. DOI:10.1021/bi982946f |
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 |
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 |
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 |
16. Aleshin AE, Stoffer B, Firsov LM, Svensson B, and Honzatko RB. (1996). Crystallographic complexes of glucoamylase with maltooligosaccharide analogs: relationship of stereochemical distortions at the nonreducing end to the catalytic mechanism. Biochemistry. 1996;35(25):8319-28. DOI:10.1021/bi960321g |
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 |