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PDBsum entry 3a3h
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Contents |
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* Residue conservation analysis
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Enzyme class:
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E.C.3.2.1.4
- cellulase.
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Reaction:
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Endohydrolysis of 1,4-beta-D-glucosidic linkages in cellulose, lichenin and cereal beta-D-glucans.
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DOI no:
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Biochemistry
37:11707-11713
(1998)
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PubMed id:
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Snapshots along an enzymatic reaction coordinate: analysis of a retaining beta-glycoside hydrolase.
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G.J.Davies,
L.Mackenzie,
A.Varrot,
M.Dauter,
A.M.Brzozowski,
M.Schülein,
S.G.Withers.
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ABSTRACT
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The enzymatic hydrolysis of O-glycosidic linkages is one of the most diverse and
widespread reactions in nature and involves a classic "textbook" enzyme
mechanism. A multidisciplinary analysis of a beta-glycoside hydrolase, the Cel5A
from Bacillus agaradhaerens, is presented in which the structures of each of the
native, substrate, covalent-intermediate, and product complexes have been
determined and their interconversions analyzed kinetically, providing
unprecedented insights into the mechanism of this enzyme class. Substrate is
bound in a distorted 1S3 skew-boat conformation, thereby presenting the anomeric
carbon appropriately for nucleophilic attack as well as satisfying the
stereoelectronic requirements for an incipient oxocarbenium ion. Leaving group
departure results in the trapping of a covalent alpha-glycosyl-enzyme
intermediate in which the sugar adopts an undistorted 4C1 conformation. Finally,
hydrolysis of this intermediate yields a product complex in which the sugar is
bound in a partially disordered mode, consistent with unfavorable interactions
and low product affinity.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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D.B.Jordan,
and
J.D.Braker
(2010).
beta-D-Xylosidase from Selenomonas ruminantium: role of glutamate 186 in catalysis revealed by site-directed mutagenesis, alternate substrates, and active-site inhibitor.
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Appl Biochem Biotechnol,
161,
395-410.
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M.Saharay,
H.Guo,
and
J.C.Smith
(2010).
Catalytic mechanism of cellulose degradation by a cellobiohydrolase, CelS.
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PLoS One,
5,
e12947.
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Y.Takaoka,
M.Ohta,
A.Takeuchi,
K.Miura,
M.Matsuo,
T.Sakaeda,
A.Sugano,
and
H.Nishio
(2010).
Ligand orientation governs conjugation capacity of UDP-glucuronosyltransferase 1A1.
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J Biochem,
148,
25-28.
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K.Eurich,
M.Segawa,
S.Toei-Shimizu,
and
E.Mizoguchi
(2009).
Potential role of chitinase 3-like-1 in inflammation-associated carcinogenic changes of epithelial cells.
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World J Gastroenterol,
15,
5249-5259.
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R.Suzuki,
Z.Fujimoto,
S.Ito,
S.Kawahara,
S.Kaneko,
K.Taira,
T.Hasegawa,
and
A.Kuno
(2009).
Crystallographic snapshots of an entire reaction cycle for a retaining xylanase from Streptomyces olivaceoviridis E-86.
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J Biochem,
146,
61-70.
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PDB codes:
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D.J.Vocadlo,
and
G.J.Davies
(2008).
Mechanistic insights into glycosidase chemistry.
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Curr Opin Chem Biol,
12,
539-555.
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T.Parkkinen,
A.Koivula,
J.Vehmaanperä,
and
J.Rouvinen
(2008).
Crystal structures of Melanocarpus albomyces cellobiohydrolase Cel7B in complex with cello-oligomers show high flexibility in the substrate binding.
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Protein Sci,
17,
1383-1394.
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PDB codes:
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A.Scaffidi,
K.A.Stubbs,
R.J.Dennis,
E.J.Taylor,
G.J.Davies,
D.J.Vocadlo,
and
R.V.Stick
(2007).
A 1-acetamido derivative of 6-epi-valienamine: an inhibitor of a diverse group of beta-N-acetylglucosaminidases.
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Org Biomol Chem,
5,
3013-3019.
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PDB code:
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J.Dechancie,
F.R.Clemente,
A.J.Smith,
H.Gunaydin,
Y.L.Zhao,
X.Zhang,
and
K.N.Houk
(2007).
How similar are enzyme active site geometries derived from quantum mechanical theozymes to crystal structures of enzyme-inhibitor complexes? Implications for enzyme design.
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Protein Sci,
16,
1851-1866.
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T.M.Gloster,
F.M.Ibatullin,
K.Macauley,
J.M.Eklöf,
S.Roberts,
J.P.Turkenburg,
M.E.Bjørnvad,
P.L.Jørgensen,
S.Danielsen,
K.S.Johansen,
T.V.Borchert,
K.S.Wilson,
H.Brumer,
and
G.J.Davies
(2007).
Characterization and three-dimensional structures of two distinct bacterial xyloglucanases from families GH5 and GH12.
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J Biol Chem,
282,
19177-19189.
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PDB codes:
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T.M.Gloster,
R.Madsen,
and
G.J.Davies
(2007).
Structural basis for cyclophellitol inhibition of a beta-glucosidase.
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Org Biomol Chem,
5,
444-446.
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PDB code:
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E.Papaleo,
P.Fantucci,
M.Vai,
and
L.De Gioia
(2006).
Three-dimensional structure of the catalytic domain of the yeast beta-(1,3)-glucan transferase Gas1: a molecular modeling investigation.
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J Mol Model,
12,
237-248.
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T.M.Gloster,
R.Madsen,
and
G.J.Davies
(2006).
Dissection of conformationally restricted inhibitors binding to a beta-glucosidase.
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Chembiochem,
7,
738-742.
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PDB codes:
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V.A.Money,
N.L.Smith,
A.Scaffidi,
R.V.Stick,
H.J.Gilbert,
and
G.J.Davies
(2006).
Substrate distortion by a lichenase highlights the different conformational itineraries harnessed by related glycoside hydrolases.
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Angew Chem Int Ed Engl,
45,
5136-5140.
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PDB codes:
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V.Receveur-Bréchot,
M.Czjzek,
A.Barre,
A.Roussel,
W.J.Peumans,
E.J.Van Damme,
and
P.Rougé
(2006).
Crystal structure at 1.45-A resolution of the major allergen endo-beta-1,3-glucanase of banana as a molecular basis for the latex-fruit syndrome.
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Proteins,
63,
235-242.
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PDB code:
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X.Biarnés,
J.Nieto,
A.Planas,
and
C.Rovira
(2006).
Substrate distortion in the Michaelis complex of Bacillus 1,3-1,4-beta-glucanase. Insight from first principles molecular dynamics simulations.
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J Biol Chem,
281,
1432-1441.
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A.L.Lovering,
S.S.Lee,
Y.W.Kim,
S.G.Withers,
and
N.C.Strynadka
(2005).
Mechanistic and structural analysis of a family 31 alpha-glycosidase and its glycosyl-enzyme intermediate.
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J Biol Chem,
280,
2105-2115.
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PDB codes:
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E.J.Taylor,
A.Goyal,
C.I.Guerreiro,
J.A.Prates,
V.A.Money,
N.Ferry,
C.Morland,
A.Planas,
J.A.Macdonald,
R.V.Stick,
H.J.Gilbert,
C.M.Fontes,
and
G.J.Davies
(2005).
How family 26 glycoside hydrolases orchestrate catalysis on different polysaccharides: structure and activity of a Clostridium thermocellum lichenase, CtLic26A.
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J Biol Chem,
280,
32761-32767.
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PDB codes:
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J.Jänis,
J.Hakanpää,
N.Hakulinen,
F.M.Ibatullin,
A.Hoxha,
P.J.Derrick,
J.Rouvinen,
and
P.Vainiotalo
(2005).
Determination of thioxylo-oligosaccharide binding to family 11 xylanases using electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry and X-ray crystallography.
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FEBS J,
272,
2317-2333.
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PDB code:
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R.Bourgault,
A.J.Oakley,
J.D.Bewley,
and
M.C.Wilce
(2005).
Three-dimensional structure of (1,4)-beta-D-mannan mannanohydrolase from tomato fruit.
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Protein Sci,
14,
1233-1241.
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PDB code:
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C.Carotti,
E.Ragni,
O.Palomares,
T.Fontaine,
G.Tedeschi,
R.Rodríguez,
J.P.Latgé,
M.Vai,
and
L.Popolo
(2004).
Characterization of recombinant forms of the yeast Gas1 protein and identification of residues essential for glucanosyltransferase activity and folding.
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Eur J Biochem,
271,
3635-3645.
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G.Kleiger,
E.M.Panina,
P.Mallick,
and
D.Eisenberg
(2004).
PFIT and PFRIT: bioinformatic algorithms for detecting glycosidase function from structure and sequence.
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Protein Sci,
13,
221-229.
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J.Allouch,
W.Helbert,
B.Henrissat,
and
M.Czjzek
(2004).
Parallel substrate binding sites in a beta-agarase suggest a novel mode of action on double-helical agarose.
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Structure,
12,
623-632.
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PDB code:
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J.K.Choi,
B.H.Lee,
C.H.Chae,
and
W.Shin
(2004).
Computer modeling of the rhamnogalacturonase-"hairy" pectin complex.
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Proteins,
55,
22-33.
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M.Hrmova,
R.De Gori,
B.J.Smith,
A.Vasella,
J.N.Varghese,
and
G.B.Fincher
(2004).
Three-dimensional structure of the barley beta-D-glucan glucohydrolase in complex with a transition state mimic.
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J Biol Chem,
279,
4970-4980.
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PDB code:
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O.J.Sul,
J.H.Kim,
S.J.Park,
Y.J.Son,
B.R.Park,
D.K.Chung,
C.S.Jeong,
and
I.S.Han
(2004).
Characterization and molecular cloning of a novel endoglucanase from Trichoderma sp. C-4.
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Appl Microbiol Biotechnol,
66,
63-70.
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T.M.Gloster,
J.M.Macdonald,
C.A.Tarling,
R.V.Stick,
S.G.Withers,
and
G.J.Davies
(2004).
Structural, thermodynamic, and kinetic analyses of tetrahydrooxazine-derived inhibitors bound to beta-glucosidases.
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J Biol Chem,
279,
49236-49242.
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PDB codes:
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A.Varrot,
and
G.J.Davies
(2003).
Direct experimental observation of the hydrogen-bonding network of a glycosidase along its reaction coordinate revealed by atomic resolution analyses of endoglucanase Cel5A.
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Acta Crystallogr D Biol Crystallogr,
59,
447-452.
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PDB codes:
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B.Aguilera,
K.Ghauharali-van der Vlugt,
M.T.Helmond,
J.M.Out,
W.E.Donker-Koopman,
J.E.Groener,
R.G.Boot,
G.H.Renkema,
G.A.van der Marel,
J.H.van Boom,
H.S.Overkleeft,
and
J.M.Aerts
(2003).
Transglycosidase activity of chitotriosidase: improved enzymatic assay for the human macrophage chitinase.
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J Biol Chem,
278,
40911-40916.
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D.Mandelman,
A.Belaich,
J.P.Belaich,
N.Aghajari,
H.Driguez,
and
R.Haser
(2003).
X-Ray crystal structure of the multidomain endoglucanase Cel9G from Clostridium cellulolyticum complexed with natural and synthetic cello-oligosaccharides.
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J Bacteriol,
185,
4127-4135.
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PDB codes:
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K.Hövel,
D.Shallom,
K.Niefind,
V.Belakhov,
G.Shoham,
T.Baasov,
Y.Shoham,
and
D.Schomburg
(2003).
Crystal structure and snapshots along the reaction pathway of a family 51 alpha-L-arabinofuranosidase.
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EMBO J,
22,
4922-4932.
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PDB codes:
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A.Varrot,
T.P.Frandsen,
H.Driguez,
and
G.J.Davies
(2002).
Structure of the Humicola insolens cellobiohydrolase Cel6A D416A mutant in complex with a non-hydrolysable substrate analogue, methyl cellobiosyl-4-thio-beta-cellobioside, at 1.9 A.
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Acta Crystallogr D Biol Crystallogr,
58,
2201-2204.
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PDB code:
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A.Vasella,
G.J.Davies,
and
M.Böhm
(2002).
Glycosidase mechanisms.
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Curr Opin Chem Biol,
6,
619-629.
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S.Khademi,
D.Zhang,
S.M.Swanson,
A.Wartenberg,
K.Witte,
and
E.F.Meyer
(2002).
Determination of the structure of an endoglucanase from Aspergillus niger and its mode of inhibition by palladium chloride.
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Acta Crystallogr D Biol Crystallogr,
58,
660-667.
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PDB codes:
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T.Kaper,
H.H.van Heusden,
B.van Loo,
A.Vasella,
J.van der Oost,
and
W.M.de Vos
(2002).
Substrate specificity engineering of beta-mannosidase and beta-glucosidase from Pyrococcus by exchange of unique active site residues.
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Biochemistry,
41,
4147-4155.
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T.P.Frandsen,
M.M.Palcic,
and
B.Svensson
(2002).
Substrate recognition by three family 13 yeast alpha-glucosidases.
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Eur J Biochem,
269,
728-734.
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A.Varrot,
M.Schülein,
S.Fruchard,
H.Driguez,
and
G.J.Davies
(2001).
Atomic resolution structure of endoglucanase Cel5A in complex with methyl 4,4II,4III,4IV-tetrathio-alpha-cellopentoside highlights the alternative binding modes targeted by substrate mimics.
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Acta Crystallogr D Biol Crystallogr,
57,
1739-1742.
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PDB code:
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B.L.Mark,
D.J.Vocadlo,
D.Zhao,
S.Knapp,
S.G.Withers,
and
M.N.James
(2001).
Biochemical and structural assessment of the 1-N-azasugar GalNAc-isofagomine as a potent family 20 beta-N-acetylhexosaminidase inhibitor.
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J Biol Chem,
276,
42131-42137.
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PDB code:
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D.M.van Aalten,
D.Komander,
B.Synstad,
S.Gåseidnes,
M.G.Peter,
and
V.G.Eijsink
(2001).
Structural insights into the catalytic mechanism of a family 18 exo-chitinase.
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Proc Natl Acad Sci U S A,
98,
8979-8984.
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PDB codes:
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M.Hrmova,
J.N.Varghese,
R.De Gori,
B.J.Smith,
H.Driguez,
and
G.B.Fincher
(2001).
Catalytic mechanisms and reaction intermediates along the hydrolytic pathway of a plant beta-D-glucan glucohydrolase.
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Structure,
9,
1005-1016.
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PDB codes:
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O.D.Schärer,
and
J.Jiricny
(2001).
Recent progress in the biology, chemistry and structural biology of DNA glycosylases.
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Bioessays,
23,
270-281.
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Y.Hou,
D.J.Vocadlo,
A.Leung,
S.G.Withers,
and
D.Mahuran
(2001).
Characterization of the Glu and Asp residues in the active site of human beta-hexosaminidase B.
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Biochemistry,
40,
2201-2209.
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A.Planas
(2000).
Bacterial 1,3-1,4-beta-glucanases: structure, function and protein engineering.
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Biochim Biophys Acta,
1543,
361-382.
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C.S.Rye,
and
S.G.Withers
(2000).
Glycosidase mechanisms.
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Curr Opin Chem Biol,
4,
573-580.
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D.O.Hart,
S.He,
C.J.Chany,
S.G.Withers,
P.F.Sims,
M.L.Sinnott,
and
H.Brumer
(2000).
Identification of Asp-130 as the catalytic nucleophile in the main alpha-galactosidase from Phanerochaete chrysosporium, a family 27 glycosyl hydrolase.
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Biochemistry,
39,
9826-9836.
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G.P.Connelly,
S.G.Withers,
and
L.P.McIntosh
(2000).
Analysis of the dynamic properties of Bacillus circulans xylanase upon formation of a covalent glycosyl-enzyme intermediate.
|
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Protein Sci,
9,
512-524.
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L.L.Leggio,
J.Jenkins,
G.W.Harris,
and
R.W.Pickersgill
(2000).
X-ray crystallographic study of xylopentaose binding to Pseudomonas fluorescens xylanase A.
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Proteins,
41,
362-373.
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PDB code:
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M.Czjzek,
M.Cicek,
V.Zamboni,
D.R.Bevan,
B.Henrissat,
and
A.Esen
(2000).
The mechanism of substrate (aglycone) specificity in beta -glucosidases is revealed by crystal structures of mutant maize beta -glucosidase-DIMBOA, -DIMBOAGlc, and -dhurrin complexes.
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Proc Natl Acad Sci U S A,
97,
13555-13560.
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PDB codes:
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S.S.Parikh,
G.Walcher,
G.D.Jones,
G.Slupphaug,
H.E.Krokan,
G.M.Blackburn,
and
J.A.Tainer
(2000).
Uracil-DNA glycosylase-DNA substrate and product structures: conformational strain promotes catalytic efficiency by coupled stereoelectronic effects.
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Proc Natl Acad Sci U S A,
97,
5083-5088.
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PDB codes:
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U.M.Unligil,
and
J.M.Rini
(2000).
Glycosyltransferase structure and mechanism.
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Curr Opin Struct Biol,
10,
510-517.
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U.M.Unligil,
S.Zhou,
S.Yuwaraj,
M.Sarkar,
H.Schachter,
and
J.M.Rini
(2000).
X-ray crystal structure of rabbit N-acetylglucosaminyltransferase I: catalytic mechanism and a new protein superfamily.
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| |
EMBO J,
19,
5269-5280.
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PDB codes:
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V.Notenboom,
S.J.Williams,
R.Hoos,
S.G.Withers,
and
D.R.Rose
(2000).
Detailed structural analysis of glycosidase/inhibitor interactions: complexes of Cex from Cellulomonas fimi with xylobiose-derived aza-sugars.
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| |
Biochemistry,
39,
11553-11563.
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PDB codes:
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Y.Hou,
D.Vocadlo,
S.Withers,
and
D.Mahuran
(2000).
Role of beta Arg211 in the active site of human beta-hexosaminidase B.
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| |
Biochemistry,
39,
6219-6227.
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Z.Marković-Housley,
G.Miglierini,
L.Soldatova,
P.J.Rizkallah,
U.Müller,
and
T.Schirmer
(2000).
Crystal structure of hyaluronidase, a major allergen of bee venom.
|
| |
Structure,
8,
1025-1035.
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PDB codes:
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A.Varrot,
M.Schülein,
and
G.J.Davies
(1999).
Structural changes of the active site tunnel of Humicola insolens cellobiohydrolase, Cel6A, upon oligosaccharide binding.
|
| |
Biochemistry,
38,
8884-8891.
|
|
|
PDB code:
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E.Sabini,
G.Sulzenbacher,
M.Dauter,
Z.Dauter,
P.L.Jørgensen,
M.Schülein,
C.Dupont,
G.J.Davies,
and
K.S.Wilson
(1999).
Catalysis and specificity in enzymatic glycoside hydrolysis: a 2,5B conformation for the glycosyl-enzyme intermediate revealed by the structure of the Bacillus agaradhaerens family 11 xylanase.
|
| |
Chem Biol,
6,
483-492.
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PDB codes:
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G.Sidhu,
S.G.Withers,
N.T.Nguyen,
L.P.McIntosh,
L.Ziser,
and
G.D.Brayer
(1999).
Sugar ring distortion in the glycosyl-enzyme intermediate of a family G/11 xylanase.
|
| |
Biochemistry,
38,
5346-5354.
|
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|
PDB codes:
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G.Sulzenbacher,
L.F.Mackenzie,
K.S.Wilson,
S.G.Withers,
C.Dupont,
and
G.J.Davies
(1999).
The crystal structure of a 2-fluorocellotriosyl complex of the Streptomyces lividans endoglucanase CelB2 at 1.2 A resolution.
|
| |
Biochemistry,
38,
4826-4833.
|
|
|
PDB code:
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J.Jiménez-Barbero,
J.L.Asensio,
F.J.Cañada,
and
A.Poveda
(1999).
Free and protein-bound carbohydrate structures.
|
| |
Curr Opin Struct Biol,
9,
549-555.
|
|
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K.Piotukh,
V.Serra,
R.Borriss,
and
A.Planas
(1999).
Protein-carbohydrate interactions defining substrate specificity in Bacillus 1,3-1,4-beta-D-glucan 4-glucanohydrolases as dissected by mutational analysis.
|
| |
Biochemistry,
38,
16092-16104.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
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