Syn/anti lateral protonation

This page is currently under construction. This means that the Responsible Curator has deemed that the page's content is not quite up to CAZypedia's standards for full public consumption. All information should be considered to be under revision and may be subject to major changes.

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

---

Overview

This page provides a table 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 a following paper by Nerinckx et al. [2].

Background

The "not from above, but from the side" concept of semi-lateral glycosidic oxygen protonation by glycoside hydrolases was introduced by Heightman and Vasella [1]. It was originally only described for beta-equatorial glycoside hydrolases, but appears to be equally applicable to enzymes acting on an alpha-axial glycosidic bond [2]. When dividing subsite -1 into half-spaces by the Ox, C1' and H1' plane of the –1 glycoside, many ligand-complexed structures show that the proton donor is positioned either in the syn half-space, near the ring-oxygen of the –1 glycoside, or in the anti half-space at the opposite side of the ring-oxygen. Members of the same GH family are always syn or always anti protonators and this specificity appears to be preserved within Clans of families. This page's compilation of subsite -1 occupied complexes shows that about 70% of all GH families are anti protonators.

Closer inspection of –1/+1 subsite-spanning ligands in crystal structures reveals a further intriguing corollary [2], [3]. In anti protonating GH enzymes, the scissile anomeric bond (often as thio-analogue) always shows a dihedral angle φ (O5'-C1'-[O,S]x-Cx) that is in the lowest-energy synclinal (gauche) position. A minus synclinal dihedral angle φ for an equatorial glycosidic bond, or plus synclinal for an axial bond [4], allows for hyperconjugative overlap of the C1'-O5' antibonding orbital with an antiperiplanar-oriented lone pair orbital lobe of the glycosidic oxygen, thereby creating partial double bond character and stabilization of the glycosidic bond by 4–5 kcal/mol; this ground-state stabilizing phenomenon is known as the ‘exo-anomeric effect’ [5] [6]. However, anti protonation occurs precisely on the oxygen’s antiperiplanar lone pair, which removes the stabilizing effect, thus providing an additional enzyme-strategy for lowering the activation barrier en route to the transition state (Figure 1 centre).

Syn protonators show a different strategy [2], [3]. In many –1/+1 subsite-spanning ligand complexes the dihedral angle φ of the scissile bond has been substantially twisted away from its lowest-energy synclinal position: clockwise to minus-anticlinal or antiperiplanar for beta-equatorial; counterclockwise to plus-anticlinal or antiperiplanar for alpha-axial anomeric bonds. This removes the hyperconjugative overlap and thus the stabilizing exo-anomeric effect. And because of this twisting, the lone pair of the glycosidic oxygen is pointing into the syn half- space, ready to be protonated by the syn-positioned proton donor (Figure 1 right).

Figure 1. Newman projections, with the glycosidic oxygen as proximal atom and the anomeric carbon as distal atom, showing anti (centre) versus syn (right) semi-lateral protonation in beta-equatorial (top) and alpha-axial (bottom) glycoside hydrolases. The indicated φ is the dihedral angle for O5'-C1'-O4-C4.

Table of syn/anti protonation examples

Note

This table contains only one example per GH family of a ligand-complexed protein structure where the syn positioning or anti positioning of the proton donor can be clearly observed; other examples may be available on a family-by-family basis. The reader is thus advised to consult the CAZy database for a current, comprehensive list of CAZyme structures. Where available, the selected examples are Michaelis-type complexes with the ligand spanning the -1/+1 subsites, since these have an intact glycosidic or thioglycosidic bond, or are N-analogs of the substrate (e.g. acarbose). In some examples, the proton donor has been mutated (e.g., to the corresponding amide or to an alanine), and in those cases one may wish to look at a superposition of the given PDB example with the structure of the native enzyme. If a Michaelis-type complex is not yet available, the second and third example choices, respectively, are trapped glycosyl-enzyme intermediates and product complexes where subsite -1 is correctly occupied.

Please also be aware that this is a large table with many data, so some (hopefully few) errors may have sneaked in. Please contact the page Author or Responsible Curator with corrections.

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 at the very top of the page.

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	[7]
GH2	A	(β/α)8	beta	retaining	anti	2vzu	exo-β-glucosaminidase	Amicolatopsis orientalis	PNP-β-d-glucosamine	Glu469	Glu541	[8]
GH3	none	(β/α)8	beta	retaining	anti	1iex	exo-1,3-1,4-glucanase	Hordeum vulgare	thiocellobiose	Glu491	Asp285	[9]
GH5	A	(β/α)8	beta	retaining	anti	1h2j	endo-β-1,4-glucanase	Bacillus agaradhaerens	2',4'-DNP-2-F-cellobioside	Glu129	Glu228	[10]
GH6	none	(β/α)8	beta	inverting	syn	1qjw	cellobiohydrolase 2	Hypocrea jecorina	(Glc)2-S-(Glc)2	Asp221	debated	[11]
GH7	B	β-jelly roll	beta	retaining	syn	1ovw	endo-1,4-glucanase	Fusarium oxysporum	thio-(Glc)5	Glu202	Glu197	[12]
GH8	M	(α/α)6	beta	inverting	anti	1kwf	endo-1,4-glucanase	Clostridium thermocellum	cellopentaose	Glu95	Asp278	[13]
GH9	none	(α/α)6	beta	inverting	syn	1rq5	cellobiohydrolase	Clostridium thermocellum	cellotetraose	Glu795	Asp383	[14]
GH10	A	(β/α)8	beta	retaining	anti	2d24	β-1,4-xylanase	Streptomyces olivaceoviridis E-86	xylopentaose	Glu128	Glu236	[15]
GH11	C	β-jelly roll	beta	retaining	syn	1bvv	xylanase	Bacillus circulans	Xyl-2-F-xylosyl	Glu172	Glu78	[16]
GH12	C	β-jelly roll	beta	retaining	syn	1w2u	endoglucanase	Humicola grisea	thiocellotetraose	Glu205	Glu120	[17]
GH13	H	(β/α)8	alpha	retaining	anti	1cxk	β-cyclodextrin glucanotransferase	Bacillus circulans	maltononaose	Glu257	Asp229	[18]
GH14	none	(β/α)8	alpha	inverting	syn	1itc	β-amylase	Bacillus cereus	maltopentaose	Glu172	Glu367	[19]
GH15	L	(α/α)6	alpha	inverting	syn	1gah	glucoamylase	Aspergillus awamori	acarbose	Glu179	Glu400	[20]
GH16	B	β-jelly roll	beta	retaining	syn	1urx	β-agarase A	Zobellia galactanivorans	oligoagarose	Glu152	Glu147	[21]
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	[22]
GH20	K	(β/α)8	beta	retaining	anti	1c7s	chitobiase	Serratia marcescens	chitobiose	Glu540	internal	[23]
GH22	none	lysozyme type	beta	retaining	syn	1h6m	lysozyme C	Gallus gallus	Chit-2-F-chitosyl	Glu35	Asp52	[24]
GH23	none	lysozyme type	beta	inverting	syn	1lsp	lysozyme G	Cygnus atratus	Bulgecin A	Glu73	internal	[25]
GH24	I	α + β	beta	inverting	syn	148l	lysozyme E	Bacteriophage T4	chitobiosyl	Glu11	Glu26	[26]
GH26	A	(β/α)8	beta	retaining	anti	1gw1	mannanase A	Cellvibrio japonicus	2',4'-DNP-2-F-cellotrioside	Glu212	Glu320	[27]
GH27	D	(β/α)8	alpha	retaining	anti	1ktc	α-N-acetyl galactosaminidase	Gallus gallus	NAGal	Asp201	Asp410	[28]
GH28	N	β-helix	alpha	inverting	anti	2uvf	exo-polygalacturonosidase	Yersinia enterocolitica ATCC9610D	digalacturonic acid	Asp402	Asp381 Asp403	[29]
GH29	none	(β/α)8	alpha	retaining	syn	1hl9	α-l-fucosidase	Thermotoga maritima	2-F-fuco- pyranosyl	Glu266	Asp224	[30]
GH30	A	(β/α)8	beta	retaining	anti	2v3d	glucocerebrosidase 1	Homo sapiens	N-butyl-deoxynojirimycin	Glu235	Glu340	[31]
GH31	D	(β/α)8	alpha	retaining	anti	2qmj	maltase-glucoamylase	Homo sapiens	acarbose	Asp542	Asp443	[32]
GH32	J	5-fold β-propeller	beta	retaining	anti	2add	fructan β-(2,1)-fructosidase	Cichorium intybus	sucrose	Glu201	Asp22	[33]
GH33	E	6-fold β-propeller	alpha	retaining	anti	1s0i	trans-sialidase	Trypanosoma cruzi	sialyl-lactose	Asp59	Tyr342	[34]
GH34	E	6-fold β-propeller	alpha	retaining	anti	2bat	neuraminidase	Influenza A virus	sialic acid	Asp151	Tyr406	[35]
GH35	A	(β/α)8	beta	retaining	anti	1xc6	β-galactosidase	Penicillium sp.	d-galactose	Glu200	Glu299	[36]
GH37	G	(α/α)6	alpha	inverting	anti	2jf4	trehalase	Escherechia coli	validoxylamine	Asp312	Glu496	[37]
GH38	none	(β/α)7	alpha	retaining	anti	1qwn	α-mannosidase II	Drosophila melanogaster	5-F-β-l-gulosyl	Asp341	Asp204	[38]
GH39	A	(β/α)8	beta	retaining	anti	1uhv	β-xylosidase	Thermoanaerobacterium saccharolyticum	2-F-xylosyl	Glu160	Glu277	[39]
GH42	A	(β/α)8	beta	retaining	anti	1kwk	β-galactosidase	Thermus thermophylus A4	d-galactose	Glu141	Glu312	[40]
GH44	none	(β/α)8	beta	retaining	anti	2eqd	endoglucanase	Clostridium thermocellum	cellooctaose	Glu186	Glu359	[41]
GH45	none	6-strand. β-barrel	beta	inverting	syn	4eng	endo-1,4-glucanase	Humicola insolens	cellohexaose	Asp121	Asp10	[42]
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	Me-2-S-(α-Man)-2-thio-α-Man	Asp463	Glu599	[43], [44]
GH48	M	(α/α)6	beta	inverting	predicted anti by clan	see at GH8
GH49	N	β-helix	alpha	inverting	predicted anti by clan	see at GH28
GH50	A	(β/α)8	beta	retaining	predicted anti by clan	see e.g. at GH1
GH51	A	(β/α)8	alpha	retaining	anti	1qw9	α-l-arabino- furanosidase	Geobacillus stearothermophilus	PNP-l-arabino-furanoside	Glu175	Glu294	[45]
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-arabinofuranose	Asp297	Glu221	[46]
GH55	none	β-helix	beta	inverting	anti	3eqo	β-1,3-glucanase	Phanerochaete chrysosporium K-3	d-gluconolacton	Glu633	unknown	[47]
GH56	none	(β/α)7	beta	retaining	anti	1fcv	hyaluronidase	Apis mellifera	(hyaluron.)4	Glu113	internal	[48]
GH57	none	(β/α)7	alpha	retaining	anti	1kly	glucanotransferase	Thermococcus litoralis	acarbose	Asp214	Glu123	[49]
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	[50]
GH68	J	5-fold β-propeller	beta	retaining	anti	1pt2	levansucrase	Bacillus subtilis	sucrose	Glu342	Asp86	[51]
GH70	H	(β/α)8	alpha	retaining	predicted anti by clan	see e.g. at GH13
GH72	A	(β/α)8	beta	retaining	anti	2w62	β-1,3-glucano- transferase	Saccharomyces cerevisiae S288C	laminaripentaose	Glu176	Glu275	[52]
GH74	none	7-fold β-propeller	beta	inverting	syn	2ebs	cellobiohydrolase (OXG-RCBH)	Geotrichum sp. m128	xyloglucan heptasaccharide	Asp465	Asp35	[53]
GH77	H	(β/α)8	alpha	retaining	anti	1esw	amylomaltase	Thermus aquaticus	acarbose	Asp395	Asp293	[54]
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
GH84	none	(β/α)8	beta	retaining	anti	2chn	β-N-acetyl- glucosaminidase	Bacteroides thetaiota- omicron VPI-5482	NAG-thiazoline	Glu242	internal	[55]
GH85	K	(β/α)8	beta	retaining	anti	2w92	endo-β-N-acetyl- glucosaminidase D	Streptococcus pneumoniae TIGR4	NAG-thiazoline	Glu337	internal	[56]
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	[57]
GH92	none	(α/α)6 + β-sandw.	alpha	inverting	anti	2ww1	α-1,2-mannosidase	Bacteroides thetaiota- omicron VPI-5482	thiomannobioside	Glu533	Asp644 Asp642	[58]
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	[59]
GH95	none	(α/α)6	alpha	inverting	anti	2ead	α-1,2-l-fucosidase	Bifidobacterium bifidum	Fuc-α-1,2-Gal	Glu566	Asn423 Asp766	[60]
GH97	none	(β/α)8	alpha	retaining + inverting	anti	2zq0	α-glucosidase	Bacteroides thetaiota- omicron VPI-5482	acarbose	Glu532	Glu508	[61]
GH102	none	double-ψ β-barrel	beta	retaining	syn	2pi8	lytic transglycosylase A	Escherechia coli	chitohexaose	Asp308	none	[62]
GH113	A	(β/α)8	beta	retaining	predicted anti by clan	see e.g. at GH1

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. Wu M, Nerinckx W, Piens K, Ishida T, Hansson H, Sandgren M, and Ståhlberg J. (2013). Rational design, synthesis, evaluation and enzyme-substrate structures of improved fluorogenic substrates for family 6 glycoside hydrolases. FEBS J. 2013;280(1):184-98. DOI:10.1111/febs.12060 |

4. Pérez S and Marchessault RH (1978) The exo-anomeric effect: experimental evidence from crystal structures. Carbohydr res 65, 114-120.

5. Cramer CJ, Truhlar DG and French AD (1997) Exo-anomeric effects on energies and geometries of different conformations of glucose and related systems in the gas phase and aqueous solution. Carbohydr res 298, 1-14.

6. Johnson GP, Petersen L, French AD, and Reilly PJ. (2009). Twisting of glycosidic bonds by hydrolases. Carbohydr Res. 2009;344(16):2157-66. DOI:10.1016/j.carres.2009.08.011 |
7. Gloster TM, Roberts S, Perugino G, Rossi M, Moracci M, Panday N, Terinek M, Vasella A, and Davies GJ. (2006). Structural, kinetic, and thermodynamic analysis of glucoimidazole-derived glycosidase inhibitors. Biochemistry. 2006;45(39):11879-84. DOI:10.1021/bi060973x |
8. van Bueren AL, Ghinet MG, Gregg K, Fleury A, Brzezinski R, and Boraston AB. (2009). The structural basis of substrate recognition in an exo-beta-D-glucosaminidase involved in chitosan hydrolysis. J Mol Biol. 2009;385(1):131-9. DOI:10.1016/j.jmb.2008.10.031 |
9. 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 |
10. 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 |
11. Zou Jy, Kleywegt GJ, Ståhlberg J, Driguez H, Nerinckx W, Claeyssens M, Koivula A, Teeri TT, and Jones TA. (1999). Crystallographic evidence for substrate ring distortion and protein conformational changes during catalysis in cellobiohydrolase Ce16A from trichoderma reesei. Structure. 1999;7(9):1035-45. DOI:10.1016/s0969-2126(99)80171-3 |
12. 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 |
13. 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 |
14. Schubot FD, Kataeva IA, Chang J, Shah AK, Ljungdahl LG, Rose JP, and Wang BC. (2004). Structural basis for the exocellulase activity of the cellobiohydrolase CbhA from Clostridium thermocellum. Biochemistry. 2004;43(5):1163-70. DOI:10.1021/bi030202i |
15. Suzuki R, Fujimoto Z, Ito S, Kawahara S, Kaneko S, Taira K, Hasegawa T, and Kuno A. (2009). Crystallographic snapshots of an entire reaction cycle for a retaining xylanase from Streptomyces olivaceoviridis E-86. J Biochem. 2009;146(1):61-70. DOI:10.1093/jb/mvp047 |
16. 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 |
17. Sandgren M, Berglund GI, Shaw A, Ståhlberg J, Kenne L, Desmet T, and Mitchinson C. (2004). Crystal complex structures reveal how substrate is bound in the -4 to the +2 binding sites of Humicola grisea Cel12A. J Mol Biol. 2004;342(5):1505-17. DOI:10.1016/j.jmb.2004.07.098 |
18. 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 |
19. Miyake H, Kurisu G, Kusunoki M, Nishimura S, Kitamura S, and Nitta Y. (2003). Crystal structure of a catalytic site mutant of beta-amylase from Bacillus cereus var. mycoides cocrystallized with maltopentaose. Biochemistry. 2003;42(19):5574-81. DOI:10.1021/bi020712x |
20. 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 |
21. 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 |
22. Papanikolau Y, Prag G, Tavlas G, Vorgias CE, Oppenheim AB, and Petratos K. (2001). High resolution structural analyses of mutant chitinase A complexes with substrates provide new insight into the mechanism of catalysis. Biochemistry. 2001;40(38):11338-43. DOI:10.1021/bi010505h |
23. Prag G, Papanikolau Y, Tavlas G, Vorgias CE, Petratos K, and Oppenheim AB. (2000). Structures of chitobiase mutants complexed with the substrate Di-N-acetyl-d-glucosamine: the catalytic role of the conserved acidic pair, aspartate 539 and glutamate 540. J Mol Biol. 2000;300(3):611-7. DOI:10.1006/jmbi.2000.3906 |
24. Vocadlo DJ, Davies GJ, Laine R, and Withers SG. (2001). Catalysis by hen egg-white lysozyme proceeds via a covalent intermediate. Nature. 2001;412(6849):835-8. DOI:10.1038/35090602 |
25. Karlsen S, Hough E, Rao ZH, and Isaacs NW. (1996). Structure of a bulgecin-inhibited g-type lysozyme from the egg white of the Australian black swan. A comparison of the binding of bulgecin to three muramidases. Acta Crystallogr D Biol Crystallogr. 1996;52(Pt 1):105-14. DOI:10.1107/S0907444995008468 |
26. Baldwin EP, Hajiseyedjavadi O, Baase WA, and Matthews BW. (1993). The role of backbone flexibility in the accommodation of variants that repack the core of T4 lysozyme. Science. 1993;262(5140):1715-8. DOI:10.1126/science.8259514 |
27. 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 |
28. Garman SC, Hannick L, Zhu A, and Garboczi DN. (2002). The 1.9 A structure of alpha-N-acetylgalactosaminidase: molecular basis of glycosidase deficiency diseases. Structure. 2002;10(3):425-34. DOI:10.1016/s0969-2126(02)00726-8 |
29. Abbott DW and Boraston AB. (2007). The structural basis for exopolygalacturonase activity in a family 28 glycoside hydrolase. J Mol Biol. 2007;368(5):1215-22. DOI:10.1016/j.jmb.2007.02.083 |
30. 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 |
31. Brumshtein B, Greenblatt HM, Butters TD, Shaaltiel Y, Aviezer D, Silman I, Futerman AH, and Sussman JL. (2007). Crystal structures of complexes of N-butyl- and N-nonyl-deoxynojirimycin bound to acid beta-glucosidase: insights into the mechanism of chemical chaperone action in Gaucher disease. J Biol Chem. 2007;282(39):29052-29058. DOI:10.1074/jbc.M705005200 |
32. Sim L, Quezada-Calvillo R, Sterchi EE, Nichols BL, and Rose DR. (2008). Human intestinal maltase-glucoamylase: crystal structure of the N-terminal catalytic subunit and basis of inhibition and substrate specificity. J Mol Biol. 2008;375(3):782-92. DOI:10.1016/j.jmb.2007.10.069 |
33. Verhaest M, Lammens W, Le Roy K, De Ranter CJ, Van Laere A, Rabijns A, and Van den Ende W. (2007). Insights into the fine architecture of the active site of chicory fructan 1-exohydrolase: 1-kestose as substrate vs sucrose as inhibitor. New Phytol. 2007;174(1):90-100. DOI:10.1111/j.1469-8137.2007.01988.x |
34. Amaya MF, Watts AG, Damager I, Wehenkel A, Nguyen T, Buschiazzo A, Paris G, Frasch AC, Withers SG, and Alzari PM. (2004). Structural insights into the catalytic mechanism of Trypanosoma cruzi trans-sialidase. Structure. 2004;12(5):775-84. DOI:10.1016/j.str.2004.02.036 |
35. Varghese JN, McKimm-Breschkin JL, Caldwell JB, Kortt AA, and Colman PM. (1992). The structure of the complex between influenza virus neuraminidase and sialic acid, the viral receptor. Proteins. 1992;14(3):327-32. DOI:10.1002/prot.340140302 |
36. Rojas AL, Nagem RA, Neustroev KN, Arand M, Adamska M, Eneyskaya EV, Kulminskaya AA, Garratt RC, Golubev AM, and Polikarpov I. (2004). Crystal structures of beta-galactosidase from Penicillium sp. and its complex with galactose. J Mol Biol. 2004;343(5):1281-92. DOI:10.1016/j.jmb.2004.09.012 |
37. Gibson RP, Gloster TM, Roberts S, Warren RA, Storch de Gracia I, García A, Chiara JL, and Davies GJ. (2007). Molecular basis for trehalase inhibition revealed by the structure of trehalase in complex with potent inhibitors. Angew Chem Int Ed Engl. 2007;46(22):4115-9. DOI:10.1002/anie.200604825 |
38. 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 |
39. Yang JK, Yoon HJ, Ahn HJ, Lee BI, Pedelacq JD, Liong EC, Berendzen J, Laivenieks M, Vieille C, Zeikus GJ, Vocadlo DJ, Withers SG, and Suh SW. (2004). Crystal structure of beta-D-xylosidase from Thermoanaerobacterium saccharolyticum, a family 39 glycoside hydrolase. J Mol Biol. 2004;335(1):155-65. DOI:10.1016/j.jmb.2003.10.026 |
40. 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 |
41. Kitago Y, Karita S, Watanabe N, Kamiya M, Aizawa T, Sakka K, and Tanaka I. (2007). Crystal structure of Cel44A, a glycoside hydrolase family 44 endoglucanase from Clostridium thermocellum. J Biol Chem. 2007;282(49):35703-11. DOI:10.1074/jbc.M706835200 |
42. Davies GJ, Dodson G, Moore MH, Tolley SP, Dauter Z, Wilson KS, Rasmussen G, and Schülein M. (1996). Structure determination and refinement of the Humicola insolens endoglucanase V at 1.5 A resolution. Acta Crystallogr D Biol Crystallogr. 1996;52(Pt 1):7-17. DOI:10.1107/S0907444995009280 |
43. 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 |
44. 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 |
45. Hövel K, Shallom D, Niefind K, Belakhov V, Shoham G, Baasov T, Shoham Y, and Schomburg D. (2003). Crystal structure and snapshots along the reaction pathway of a family 51 alpha-L-arabinofuranosidase. EMBO J. 2003;22(19):4922-32. DOI:10.1093/emboj/cdg494 |
46. Miyanaga A, Koseki T, Matsuzawa H, Wakagi T, Shoun H, and Fushinobu S. (2004). Crystal structure of a family 54 alpha-L-arabinofuranosidase reveals a novel carbohydrate-binding module that can bind arabinose. J Biol Chem. 2004;279(43):44907-14. DOI:10.1074/jbc.M405390200 |
47. Ishida T, Fushinobu S, Kawai R, Kitaoka M, Igarashi K, and Samejima M. (2009). Crystal structure of glycoside hydrolase family 55 {beta}-1,3-glucanase from the basidiomycete Phanerochaete chrysosporium. J Biol Chem. 2009;284(15):10100-9. DOI:10.1074/jbc.M808122200 |

48. Marković-Housley Z, Miglierini G, Soldatova L, Rizkallah PJ, Müller U, Schirmer T. Crystal structure of hyaluronidase, a major allergen of bee venom. Structure. 2000 Oct 15;8(10):1025-35.

    Note: Due to a problem with PubMed data, this reference is not automatically formatted. Please see these links out: DOI:10.1016/S0969-2126(00)00511-6 PMID:11080624

49. 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 |
50. Nurizzo D, Nagy T, Gilbert HJ, and Davies GJ. (2002). The structural basis for catalysis and specificity of the Pseudomonas cellulosa alpha-glucuronidase, GlcA67A. Structure. 2002;10(4):547-56. DOI:10.1016/s0969-2126(02)00742-6 |
51. Meng G and Fütterer K. (2003). Structural framework of fructosyl transfer in Bacillus subtilis levansucrase. Nat Struct Biol. 2003;10(11):935-41. DOI:10.1038/nsb974 |
52. Hurtado-Guerrero R, Schüttelkopf AW, Mouyna I, Ibrahim AF, Shepherd S, Fontaine T, Latgé JP, and van Aalten DM. (2009). Molecular mechanisms of yeast cell wall glucan remodeling. J Biol Chem. 2009;284(13):8461-9. DOI:10.1074/jbc.M807990200 |
53. Yaoi K, Kondo H, Hiyoshi A, Noro N, Sugimoto H, Tsuda S, Mitsuishi Y, and Miyazaki K. (2007). The structural basis for the exo-mode of action in GH74 oligoxyloglucan reducing end-specific cellobiohydrolase. J Mol Biol. 2007;370(1):53-62. DOI:10.1016/j.jmb.2007.04.035 |
54. 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 |
55. Dennis RJ, Taylor EJ, Macauley MS, Stubbs KA, Turkenburg JP, Hart SJ, Black GN, Vocadlo DJ, and Davies GJ. (2006). Structure and mechanism of a bacterial beta-glucosaminidase having O-GlcNAcase activity. Nat Struct Mol Biol. 2006;13(4):365-71. DOI:10.1038/nsmb1079 |
56. Abbott DW, Macauley MS, Vocadlo DJ, and Boraston AB. (2009). Streptococcus pneumoniae endohexosaminidase D, structural and mechanistic insight into substrate-assisted catalysis in family 85 glycoside hydrolases. J Biol Chem. 2009;284(17):11676-89. DOI:10.1074/jbc.M809663200 |
57. Ficko-Blean E, Stubbs KA, Nemirovsky O, Vocadlo DJ, and Boraston AB. (2008). Structural and mechanistic insight into the basis of mucopolysaccharidosis IIIB. Proc Natl Acad Sci U S A. 2008;105(18):6560-5. DOI:10.1073/pnas.0711491105 |

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

59. Hidaka M, Honda Y, Kitaoka M, Nirasawa S, Hayashi K, Wakagi T, Shoun H, and Fushinobu S. (2004). Chitobiose phosphorylase from Vibrio proteolyticus, a member of glycosyl transferase family 36, has a clan GH-L-like (alpha/alpha)(6) barrel fold. Structure. 2004;12(6):937-47. DOI:10.1016/j.str.2004.03.027 |
60. Nagae M, Tsuchiya A, Katayama T, Yamamoto K, Wakatsuki S, and Kato R. (2007). Structural basis of the catalytic reaction mechanism of novel 1,2-alpha-L-fucosidase from Bifidobacterium bifidum. J Biol Chem. 2007;282(25):18497-18509. DOI:10.1074/jbc.M702246200 |
61. Kitamura M, Okuyama M, Tanzawa F, Mori H, Kitago Y, Watanabe N, Kimura A, Tanaka I, and Yao M. (2008). Structural and functional analysis of a glycoside hydrolase family 97 enzyme from Bacteroides thetaiotaomicron. J Biol Chem. 2008;283(52):36328-37. DOI:10.1074/jbc.M806115200 |
62. van Straaten KE, Barends TR, Dijkstra BW, and Thunnissen AM. (2007). Structure of Escherichia coli Lytic transglycosylase MltA with bound chitohexaose: implications for peptidoglycan binding and cleavage. J Biol Chem. 2007;282(29):21197-205. DOI:10.1074/jbc.M701818200 |