DB code: S00162

RLCP classification 1.30.36210.990 : Hydrolysis
CATH domain 2.70.100.10 : 1,4-Beta-D-Glucan Cellobiohydrolase I; Chain A Catalytic domain
E.C. 3.2.1.4
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
2.70.100.10 : 1,4-Beta-D-Glucan Cellobiohydrolase I; Chain A D00499

Uniprot Enzyme Name
UniprotKB Protein name Synonyms CAZy Pfam
P56680 Endoglucanase 1
EC 3.2.1.4
Endoglucanase I
Endo-1,4-beta-glucanase 1
Cellulase 1
GH7 (Glycoside Hydrolase Family 7)
PF00840 (Glyco_hydro_7)
[Graphical View]
P46237 Endoglucanase type C
EC 3.2.1.4
Endo-1,4-beta-glucanase
Endoglucanase I
EG I
Cellulase
GH7 (Glycoside Hydrolase Family 7)
PF00840 (Glyco_hydro_7)
[Graphical View]

KEGG enzyme name
cellulase
endo-1,4-beta-D-glucanase
beta-1,4-glucanase
beta-1,4-endoglucan hydrolase
celluase A
cellulosin AP
endoglucanase D
alkali cellulase
cellulase A 3
celludextrinase
9.5 cellulase
avicelase
pancellase SS
1,4-(1,3
1,4)-beta-D-glucan 4-glucanohydrolase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P56680 GUN1_HUMIN Endohydrolysis of (1->4)-beta-D-glucosidic linkages in cellulose, lichenin and cereal beta-D-glucans. Monomer. Secreted.
P46237 GUNC_FUSOX Endohydrolysis of (1->4)-beta-D-glucosidic linkages in cellulose, lichenin and cereal beta-D-glucans.

KEGG Pathways
Map code Pathways E.C.
MAP00500 Starch and sucrose metabolism

Compound table
Substrates Products Intermediates
KEGG-id C00760 C00478 C00551 C00001 C00760 C00551
E.C.
Compound Cellulose Lichenin beta-D-Glucan H2O Cellulose beta-D-Glucan Transition-state in glycosylation Glycosyl-enzyme intermediate Transition-state in deglycosylation
Type polysaccharide carbohydrate polysaccharide H2O polysaccharide polysaccharide
ChEBI 15377
PubChem 439241
46173706
22247451
962
46173706
1a39A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1dymA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1ojiA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1ojjA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Analogue:GAL-GLC Analogue:GAL-BGC Unbound
1ojjB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Analogue:GAL-GLC Analogue:GAL-BGC Unbound
1ojkA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Analogue:BGC-GLC Bound:BGC-BGC Unbound
1ojkB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Analogue:BGC-GLC Bound:BGC-BGC Unbound
2a39A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
2a39B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1ovwA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:DP5 Unbound Unbound Unbound Unbound Unbound
1ovwB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:DP5 Unbound Unbound Unbound Unbound Unbound
1ovwC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:DP5 Unbound Unbound Unbound Unbound Unbound
1ovwD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:DP5 Unbound Unbound Unbound Unbound Unbound
2ovwA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Bound:CBI Unbound Unbound
2ovwB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Bound:CBI Unbound Unbound
2ovwC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Bound:CBI Unbound Unbound
2ovwD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Bound:CBI Unbound Unbound
3ovwA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
3ovwB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
4ovwA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:IN1
4ovwB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:IN1

Reference for Active-site residues
resource references E.C.
literature [11]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1a39A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 197;ASP 199;GLU 202;HIS 213 mutant S37W, P39W
1dymA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ;ASP 199;GLU 202;HIS 213 mutant E197A
1ojiA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ;ASP 199;GLU 202;HIS 213 mutant E197S
1ojjA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ;ASP 199;GLU 202;HIS 213 mutant E197S
1ojjB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ;ASP 199;GLU 202;HIS 213 mutant E197S
1ojkA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ;ASP 199;GLU 202;HIS 213 mutant E197S
1ojkB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ;ASP 199;GLU 202;HIS 213 mutant E197S
2a39A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 197;ASP 199;GLU 202;HIS 213
2a39B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 197;ASP 199;GLU 202;HIS 213
1ovwA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 197;ASP 199;GLU 202;HIS 213
1ovwB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 197;ASP 199;GLU 202;HIS 213
1ovwC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 197;ASP 199;GLU 202;HIS 213
1ovwD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 197;ASP 199;GLU 202;HIS 213
2ovwA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 197;ASP 199;GLU 202;HIS 213
2ovwB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 197;ASP 199;GLU 202;HIS 213
2ovwC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 197;ASP 199;GLU 202;HIS 213
2ovwD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 197;ASP 199;GLU 202;HIS 213
3ovwA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 197;ASP 199;GLU 202;HIS 213
3ovwB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 197;ASP 199;GLU 202;HIS 213
4ovwA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 197;ASP 199;GLU 202;HIS 213
4ovwB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 197;ASP 199;GLU 202;HIS 213

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[5]
Fig.1, Fig.7, p.15284-15285
[7]
Fig.1, p.5900
[8]
Fig.4, p.5909-5910
[11]
p.388-389
[12]
Scheme 1, p.415-416
[13]
Scheme 1, p.27
[14]
p.1101
[15]
Fig.1, p.622-624

References
[1]
Resource
Comments
Medline ID
PubMed ID
Journal FEBS Lett
Year 1989
Volume 243
Pages 239-43
Authors Tomme P, Clayssens M
Title Identification of a functionally important carboxyl group in cellobiohydrolase I from Trichoderma reesei.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 2396985
Journal Biochem J
Year 1990
Volume 270
Pages 251-6
Authors Claeyssens M, van Tilbeurgh H, Kamerling JP, Berg J, Vrsanska M, Biely P
Title Studies of the cellulolytic system of the filamentous fungus Trichoderma reesei QM 9414. Substrate specificity and transfer activity of endoglucanase I.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 2261982
Journal FEBS Lett
Year 1990
Volume 275
Pages 135-8
Authors Mitsuishi Y, Nitisinprasert S, Saloheimo M, Biese I, Reinikainen T, Claeyssens M, Keranen S, Knowles JK, Teeri TT
Title Site-directed mutagenesis of the putative catalytic residues of Trichoderma reesei cellobiohydrolase I and endoglucanase I.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 8223652
Journal Eur J Biochem
Year 1993
Volume 217
Pages 947-53
Authors Schou C, Rasmussen G, Kaltoft MB, Henrissat B, Schulein M
Title Stereochemistry, specificity and kinetics of the hydrolysis of reduced cellodextrins by nine cellulases.
Related PDB
Related UniProtKB
[5]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS).
Medline ID 97110317
PubMed ID 8952478
Journal Biochemistry
Year 1996
Volume 35
Pages 15280-7
Authors Sulzenbacher G, Driguez H, Henrissat B, Schulein M, Davies GJ
Title 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.
Related PDB 1ovw
Related UniProtKB P46237
[6]
Resource
Comments
Medline ID
PubMed ID 8706890
Journal FEBS Lett
Year 1996
Volume 390
Pages 339-44
Authors Henriksson H, Stahlberg J, Isaksson R, Pettersson G
Title The active sites of cellulases are involved in chiral recognition: a comparison of cellobiohydrolase 1 and endoglucanase 1.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 9153431
Journal Biochemistry
Year 1997
Volume 36
Pages 5893-901
Authors Mackenzie LF, Davies GJ, Schulein M, Withers SG
Title Identification of the catalytic nucleophile of endoglucanase I from Fusarium oxysporum by mass spectrometry.
Related PDB
Related UniProtKB
[8]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
Medline ID 97297800
PubMed ID 9153432
Journal Biochemistry
Year 1997
Volume 36
Pages 5902-11
Authors Sulzenbacher G, Schulein M, Davies GJ
Title Structure of the endoglucanase I from Fusarium oxysporum: native, cellobiose, and 3,4-epoxybutyl beta-D-cellobioside-inhibited forms, at 2.3 A resolution.
Related PDB 2ovw 3ovw 4ovw
Related UniProtKB P46237
[9]
Resource
Comments
Medline ID
PubMed ID 9006908
Journal J Biol Chem
Year 1997
Volume 272
Pages 2709-13
Authors Armand S, Drouillard S, Schulein M, Henrissat B, Driguez H
Title A bifunctionalized fluorogenic tetrasaccharide as a substrate to study cellulases.
Related PDB
Related UniProtKB
[10]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF MUTANT S37W/P39W.
Medline ID 97475713
PubMed ID 9335168
Journal J Biotechnol
Year 1997
Volume 57
Pages 91-100
Authors Davies GJ, Ducros V, Lewis RJ, Borchert TV, Schulein M
Title Oligosaccharide specificity of a family 7 endoglucanase: insertion of potential sugar-binding subsites.
Related PDB 1a39
Related UniProtKB P56680
[11]
Resource
Comments
Medline ID
PubMed ID 9325098
Journal J Mol Biol
Year 1997
Volume 272
Pages 383-97
Authors Kleywegt GJ, Zou JY, Divne C, Davies GJ, Sinning I, Stahlberg J, Reinikainen T, Srisodsuk M, Teeri TT, Jones TA
Title The crystal structure of the catalytic core domain of endoglucanase I from Trichoderma reesei at 3.6 A resolution, and a comparison with related enzymes.
Related PDB
Related UniProtKB
[12]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS), AND MUTAGENESIS.
Medline ID 98437137
PubMed ID 9761741
Journal Biochem J
Year 1998
Volume 335
Pages 409-16
Authors MacKenzie LF, Sulzenbacher G, Divne C, Jones TA, Woldike HF, Schulein M, Withers SG, Davies GJ
Title Crystal structure of the family 7 endoglucanase I (Cel7B) from Humicola insolens at 2.2 A resolution and identification of the catalytic nucleophile by trapping of the covalent glycosyl-enzyme intermediate.
Related PDB 1dym 2a39
Related UniProtKB P56680
[13]
Resource
Comments
Medline ID
PubMed ID 11336632
Journal Biochem J
Year 2001
Volume 356
Pages 19-30
Authors Becker D, Braet C, Brumer H 3rd, Claeyssens M, Divne C, Fagerstrom BR, Harris M, Jones TA, Kleywegt GJ, Koivula A, Mahdi S, Piens K, Sinnott ML, Stahlberg J, Teeri TT, Underwood M, Wohlfahrt G
Title Engineering of a glycosidase Family 7 cellobiohydrolase to more alkaline pH optimum: the pH behaviour of Trichoderma reesei Cel7A and its E223S/ A224H/L225V/T226A/D262G mutant.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 11743726
Journal J Mol Biol
Year 2001
Volume 314
Pages 1097-111
Authors Munoz IG, Ubhayasekera W, Henriksson H, Szabo I, Pettersson G, Johansson G, Mowbray SL, Stahlberg J
Title Family 7 cellobiohydrolases from Phanerochaete chrysosporium: crystal structure of the catalytic module of Cel7D (CBH58) at 1.32 A resolution and homology models of the isozymes.
Related PDB
Related UniProtKB
[15]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 12890535
Journal Chem Biol
Year 2003
Volume 10
Pages 619-28
Authors Ducros VM, Tarling CA, Zechel DL, Brzozowski AM, Frandsen TP, von Ossowski I, Schulein M, Withers SG, Davies GJ
Title Anatomy of glycosynthesis: structure and kinetics of the Humicola insolens Cel7B E197A and E197S glycosynthase mutants.
Related PDB 1oji 1ojj 1ojk
Related UniProtKB

Comments
This enzyme belongs to the glycosidase family-7.
According to the literature [7], [8], [11], [12] & [14], the catalytic reaction proceeds as follows:
(0) Asp199 modulates the pKa of Glu197, which is a nucleophile. His213 modulates these residues, Asp199 and Glu197.
(1) Glu202 acts as a general acid, to protonate the leaving group, through a water molecule, to give an oxacarbenium ion-like transition state. (SN1-like reaction)
(2) Glu197 makes a nucleophilic attack on the C2 atom of the transition-state, to form a glycosyl-enzyme intermediate.
(3) Glu202 acts as a general base, to activate the water.
(4) The activated water makes a nucleophilic attack on the intermediate, through an oxacarbenium ion-like transition-state, to complete the hydrolysis.

Created Updated
2004-03-22 2009-02-26