DB code: D00537

RLCP classification 1.30.300.2 : Hydrolysis
CATH domain 2.-.-.- :
3.20.20.40 : TIM Barrel Catalytic domain
E.C. 3.2.1.91
CSA 1qk2
M-CSA 1qk2
MACiE

CATH domain Related DB codes (homologues)
3.20.20.40 : TIM Barrel S00194 D00536

Uniprot Enzyme Name
UniprotKB Protein name Synonyms CAZy Pfam
P07987 Exoglucanase 2
EC 3.2.1.91
Exoglucanase II
Exocellobiohydrolase II
CBHII
1,4-beta-cellobiohydrolase
CBM1 (Carbohydrate-Binding Module Family 1)
GH6 (Glycoside Hydrolase Family 6)
PF00734 (CBM_1)
PF01341 (Glyco_hydro_6)
[Graphical View]
Q9C1S9 Exoglucanase-6A
EC 3.2.1.91
Exocellobiohydrolase 6A
1,4-beta-cellobiohydrolase 6A
Beta-glucancellobiohydrolase 6A
Avicelase 2
CBM1 (Carbohydrate-Binding Module Family 1)
GH6 (Glycoside Hydrolase Family 6)
PF00734 (CBM_1)
PF01341 (Glyco_hydro_6)
[Graphical View]

KEGG enzyme name
cellulose 1,4-beta-cellobiosidase
exo-cellobiohydrolase
beta-1,4-glucan cellobiohydrolase
beta-1,4-glucan cellobiosylhydrolase
1,4-beta-glucan cellobiosidase
exoglucanase
avicelase
CBH 1
C1 cellulase
cellobiohydrolase I
cellobiohydrolase
exo-beta-1,4-glucan cellobiohydrolase
1,4-beta-D-glucan cellobiohydrolase
cellobiosidase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P07987 GUX2_TRIRE Hydrolysis of 1,4-beta-D-glucosidic linkages in cellulose and cellotetraose, releasing cellobiose from the non- reducing ends of the chains. Secreted.
Q9C1S9 GUX6_HUMIN Hydrolysis of 1,4-beta-D-glucosidic linkages in cellulose and cellotetraose, releasing cellobiose from the non- reducing ends of the chains. Monomer.

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

Compound table
Substrates Products Intermediates
KEGG-id C00760 C02013 C00001 C00185 C00760
E.C.
Compound Cellulose Cellotetraose H2O Cellobiose Cellulose
Type polysaccharide polysaccharide H2O polysaccharide polysaccharide
ChEBI 62974
15377
17057
PubChem 439626
22247451
962
439178
1cb2A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1cb2B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1qjwA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Analogue:GLC-GLC-SGC-MGL Unbound Unbound
1qjwB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Analogue:GLC-GLC-SGC-MGL Unbound Unbound
1qk0A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Analogue:GLC-XYS-IOB Unbound Unbound
1qk0B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Analogue:GLC-XYS-IOB Unbound Unbound
1qk2A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Analogue:GLC-GLC-SGC-MGL Unbound Unbound
1qk2B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Analogue:GLC-GLC-SGC-MGL Unbound Unbound
1bvwA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
2bvwA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:HOH_97 Analogue:CTT Analogue:GLC_602
2bvwB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:HOH_431 Analogue:CT3 Analogue:GLC_603

Reference for Active-site residues
resource references E.C.
literature [15]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1cb2A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 175;ASP 221;ASP 263;ASP 401 mutant Y169F
1cb2B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 175;ASP 221;ASP 263;ASP 401 mutant Y169F
1qjwA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 175;ASP 221;ASP 263;ASP 401 mutant Y169F
1qjwB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 175;ASP 221;ASP 263;ASP 401 mutant Y169F
1qk0A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 175;ASP 221;ASP 263;ASP 401
1qk0B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 175;ASP 221;ASP 263;ASP 401
1qk2A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 175;ASP 221;ASP 263;ASP 401
1qk2B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 175;ASP 221;ASP 263;ASP 401
1bvwA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 180;ASP 226;ASP 268;ASP 405
2bvwA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 180;ASP 226;ASP 268;ASP 405
2bvwB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 180;ASP 226;ASP 268;ASP 405

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[14]
Scheme 1 1
[15]
Fig.6, Fig.7, p.8888-8890 1

References
[1]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
Medline ID 90333255
PubMed ID 2377893
Journal Science
Year 1990
Volume 249
Pages 380-6
Authors Rouvinen J, Bergfors T, Teeri T, Knowles JK, Jones TA
Title Three-dimensional structure of cellobiohydrolase II from Trichoderma reesei.
Related PDB
Related UniProtKB P07987
[2]
Resource
Comments
Medline ID
PubMed ID 1761039
Journal Eur J Biochem
Year 1991
Volume 202
Pages 367-77
Authors Gilkes NR, Claeyssens M, Aebersold R, Henrissat B, Meinke A, Morrison HD, Kilburn DG, Warren RA, Miller RC Jr
Title Structural and functional relationships in two families of beta-1,4-glycanases.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 8399160
Journal Biochemistry
Year 1993
Volume 32
Pages 9906-16
Authors Spezio M, Wilson DB, Karplus PA
Title Crystal structure of the catalytic domain of a thermophilic endocellulase.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 8192865
Journal Biotechnol Appl Biochem
Year 1994
Volume 19
Pages 141-53
Authors Woodward J, Brown JP, Evans BR, Affholter KA
Title Papain digestion of crude Trichoderma reesei cellulase: purification and properties of cellobiohydrolase I and II core proteins.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 7733957
Journal Biochem Biophys Res Commun
Year 1995
Volume 209
Pages 1046-52
Authors Shultz MD, Lassig JP, Gooch MG, Evans BR, Woodward J
Title Palladium--a new inhibitor of cellulase activities.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 7857933
Journal Biochemistry
Year 1995
Volume 34
Pages 2220-4
Authors Damude HG, Withers SG, Kilburn DG, Miller RC Jr, Warren RA
Title Site-directed mutation of the putative catalytic residues of endoglucanase CenA from Cellulomonas fimi.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 8615816
Journal Biochem J
Year 1996
Volume 315
Pages 467-72
Authors Damude HG, Ferro V, Withers SG, Warren RA
Title Substrate specificity of endoglucanase A from Cellulomonas fimi: fundamental differences between endoglucanases and exoglucanases from family 6.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 8856058
Journal Eur J Biochem
Year 1996
Volume 240
Pages 584-91
Authors Harjunpaa V, Teleman A, Koivula A, Ruohonen L, Teeri TT, Teleman O, Drakenberg T
Title Cello-oligosaccharide hydrolysis by cellobiohydrolase II from Trichoderma reesei. Association and rate constants derived from an analysis of progress curves.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 9010760
Journal J Biochem (Tokyo)
Year 1996
Volume 120
Pages 1123-9
Authors Amano Y, Shiroishi M, Nisizawa K, Hoshino E, Kanda T
Title Fine substrate specificities of four exo-type cellulases produced by Aspergillus niger, Trichoderma reesei, and Irpex lacteus on (1-->3), (1-->4)-beta-D-glucans and xyloglucan.
Related PDB
Related UniProtKB
[10]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
Medline ID 97029636
PubMed ID 8875646
Journal Protein Eng
Year 1996
Volume 9
Pages 691-9
Authors Koivula A, Reinikainen T, Ruohonen L, Valkeajarvi A, Claeyssens M, Teleman O, Kleywegt GJ, Szardenings M, Rouvinen J, Jones TA, Teeri TT
Title The active site of Trichoderma reesei cellobiohydrolase II: the role of tyrosine 169.
Related PDB 1cb2
Related UniProtKB P07987
[11]
Resource
Comments
Medline ID
PubMed ID 8959766
Journal Protein Expr Purif
Year 1996
Volume 8
Pages 399-400
Authors Koivula A, Lappalainen A, Virtanen S, Mantyla AL, Suominen P, Teeri TT
Title Immunoaffinity chromatographic purification of cellobiohydrolase II mutants from recombinant trichoderma reesei strains devoid of major endoglucanase genes.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 9204518
Journal Appl Biochem Biotechnol
Year 1997
Volume 66
Pages 39-56
Authors Medve J, Stahlberg J, Tjerneld F
Title Isotherms for adsorption of cellobiohydrolase I and II from Trichoderma reesei on microcrystalline cellulose.
Related PDB
Related UniProtKB
[13]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 9662445
Journal FEBS Lett
Year 1998
Volume 429
Pages 341-6
Authors Koivula A, Kinnari T, Harjunpaa V, Ruohonen L, Teleman A, Drakenberg T, Rouvinen J, Jones TA, Teeri TT
Title Tryptophan 272: an essential determinant of crystalline cellulose degradation by Trichoderma reesei cellobiohydrolase Cel6A.
Related PDB 1bvw
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 9882628
Journal Biochem J
Year 1999
Volume 337
Pages 297-304
Authors Varrot A, Hastrup S, Schulein M, Davies GJ
Title Crystal structure of the catalytic core domain of the family 6 cellobiohydrolase II, Cel6A, from Humicola insolens, at 1.92 A resolution.
Related PDB
Related UniProtKB
[15]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10413461
Journal Biochemistry
Year 1999
Volume 38
Pages 8884-91
Authors Varrot A, Schulein M, Davies GJ
Title Structural changes of the active site tunnel of Humicola insolens cellobiohydrolase, Cel6A, upon oligosaccharide binding.
Related PDB 2bvw
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 10411622
Journal Eur J Biochem
Year 1999
Volume 262
Pages 637-43
Authors Carrard G, Linder M
Title Widely different off rates of two closely related cellulose-binding domains from Trichoderma reesei.
Related PDB
Related UniProtKB
[17]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10508787
Journal Structure Fold Des
Year 1999
Volume 7
Pages 1035-45
Authors Zou J, Kleywegt GJ, Stahlberg J, Driguez H, Nerinckx W, Claeyssens M, Koivula A, Teeri TT, Jones TA
Title Crystallographic evidence for substrate ring distortion and protein conformational changes during catalysis in cellobiohydrolase Ce16A from trichoderma reesei.
Related PDB 1qk0 1qk2 1qjw
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 10794732
Journal Biochem J
Year 2000
Volume 348 Pt 1
Pages 201-7
Authors Davies GJ, Brzozowski AM, Dauter M, Varrot A, Schulein M
Title Structure and function of Humicola insolens family 6 cellulases: structure of the endoglucanase, Cel6B, at 1.6 A resolution.
Related PDB
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 10601873
Journal Eur J Biochem
Year 2000
Volume 267
Pages 244-52
Authors Zhang S, Barr BK, Wilson DB
Title Effects of noncatalytic residue mutations on substrate specificity and ligand binding of Thermobifida fusca endocellulase cel6A.
Related PDB
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID 11179652
Journal FEMS Microbiol Lett
Year 2001
Volume 195
Pages 197-204
Authors Lehtio J, Wernerus H, Samuelson P, Teeri TT, Stahl S
Title Directed immobilization of recombinant staphylococci on cotton fibers by functional display of a fungal cellulose-binding domain.
Related PDB
Related UniProtKB
[21]
Resource
Comments
Medline ID
PubMed ID 11325554
Journal FEMS Microbiol Lett
Year 2001
Volume 198
Pages 57-63
Authors Limon MC, Margolles-Clark E, Benitez T, Penttila M
Title Addition of substrate-binding domains increases substrate-binding capacity and specific activity of a chitinase from Trichoderma harzianum.
Related PDB
Related UniProtKB
[22]
Resource
Comments
Medline ID
PubMed ID 12007616
Journal Biochim Biophys Acta
Year 2002
Volume 1596
Pages 366-80
Authors Tuohy MG, Walsh DJ, Murray PG, Claeyssens M, Cuffe MM, Savage AV, Coughlan MP
Title Kinetic parameters and mode of action of the cellobiohydrolases produced by Talaromyces emersonii.
Related PDB
Related UniProtKB
[23]
Resource
Comments
Medline ID
PubMed ID 12188666
Journal J Am Chem Soc
Year 2002
Volume 124
Pages 10015-24
Authors Koivula A, Ruohonen L, Wohlfahrt G, Reinikainen T, Teeri TT, Piens K, Claeyssens M, Weber M, Vasella A, Becker D, Sinnott ML, Zou JY, Kleywegt GJ, Szardenings M, Stahlberg J, Jones TA
Title The active site of cellobiohydrolase Cel6A from Trichoderma reesei: the roles of aspartic acids D221 and D175.
Related PDB
Related UniProtKB
[24]
Resource
Comments
Medline ID
PubMed ID 12565856
Journal Biochem Biophys Res Commun
Year 2003
Volume 301
Pages 280-6
Authors Murray PG, Collins CM, Grassick A, Tuohy MG
Title Molecular cloning, transcriptional, and expression analysis of the first cellulase gene (cbh2), encoding cellobiohydrolase II, from the moderately thermophilic fungus Talaromyces emersonii and structure prediction of the gene product.
Related PDB
Related UniProtKB

Comments
The literature [15] confirmed that Asp226 (2bvw) atcs as proton donor (acid catalyst) and Asp405 as the catalytic base. In sharp contrast, the literature [6] doubted the role of Asp405, which suggests Asp268 might act as base catalyst. In any case, the identification of catalytic base is difficult for these enzymes.
This family belongs to Glycosidase family-6, which has an inverting mechanism (equatorial to axial conformation). Furthermore, this enzyme belongs to exoglucanase, which requrires polymer-chain ends for catalytic activity, whilst its family member (EC 3.2.1.4) is endoglucanase.
The literature [7] suggests that endoglucanases from this family-6 may function by different mechanisms from this exoglucanase from the same family.

Created Updated
2002-10-15 2009-09-29