D00502
type: Enzyme
rlcp: p972
cath: TIM Barrel
cath: Immunoglobulin-like
ec: https://purl.uniprot.org/enzyme/3.2.1.4
uniprot: P54583
kegg enzyme: cellulase
kegg enzyme: endo-1,4-beta-D-glucanase
kegg enzyme: beta-1,4-glucanase
kegg enzyme: beta-1,4-endoglucan hydrolase
kegg enzyme: celluase A
kegg enzyme: cellulosin AP
kegg enzyme: endoglucanase D
kegg enzyme: alkali cellulase
kegg enzyme: cellulase A 3
kegg enzyme: celludextrinase
kegg enzyme: 9.5 cellulase
kegg enzyme: avicelase
kegg enzyme: pancellase SS
kegg enzyme: 1,4-(1,3
kegg enzyme: 1,4)-beta-D-glucan 4-glucanohydrolase
kegg pathway: Starch and sucrose metabolism
kegg substrate: Cellulose
kegg substrate: H2O
kegg substrate: Lichenin
kegg substrate: beta-D-Glucan
kegg product: Cellulose
kegg product: beta-D-Glucan
kegg intermediate: Peptidyl-Glu-cellulose
pdb: 1c0dA
pdb: 1c0dB
pdb: 1eceA
pdb: 1eceB
pdb: 1vrxA
pdb: 1vrxB
pdb bound state: Unbound
  compound: Cellulose
  pdb: 1c0dA
pdb bound state: Unbound
  compound: Cellulose
  pdb: 1c0dB
pdb bound state: Analogue
  compound: Cellulose
  pdb: 1eceA
  ligand het code: GLC-GLC-GLC-GLC
pdb bound state: Analogue
  compound: Cellulose
  pdb: 1eceB
  ligand het code: GLC-GLC-GLC-GLC
pdb bound state: Unbound
  compound: Cellulose
  pdb: 1vrxA
pdb bound state: Unbound
  compound: Cellulose
  pdb: 1vrxB
pdb bound state: Unbound
  compound: Lichenin
  pdb: 1c0dA
pdb bound state: Unbound
  compound: Lichenin
  pdb: 1c0dB
pdb bound state: Unbound
  compound: Lichenin
  pdb: 1eceA
pdb bound state: Unbound
  compound: Lichenin
  pdb: 1eceB
pdb bound state: Unbound
  compound: Lichenin
  pdb: 1vrxA
pdb bound state: Unbound
  compound: Lichenin
  pdb: 1vrxB
pdb bound state: Unbound
  compound: beta-D-Glucan
  pdb: 1c0dA
pdb bound state: Unbound
  compound: beta-D-Glucan
  pdb: 1c0dB
pdb bound state: Unbound
  compound: beta-D-Glucan
  pdb: 1vrxA
pdb bound state: Unbound
  compound: beta-D-Glucan
  pdb: 1vrxB
pdb bound state: Unbound
  compound: Cellulose
  pdb: 1c0dA
pdb bound state: Unbound
  compound: Cellulose
  pdb: 1c0dB
pdb bound state: Unbound
  compound: Cellulose
  pdb: 1eceA
pdb bound state: Unbound
  compound: Cellulose
  pdb: 1eceB
pdb bound state: Unbound
  compound: Cellulose
  pdb: 1vrxA
pdb bound state: Unbound
  compound: Cellulose
  pdb: 1vrxB
pdb bound state: Unbound
  compound: beta-D-Glucan
  pdb: 1c0dA
pdb bound state: Unbound
  compound: beta-D-Glucan
  pdb: 1c0dB
pdb bound state: Unbound
  compound: beta-D-Glucan
  pdb: 1eceA
pdb bound state: Unbound
  compound: beta-D-Glucan
  pdb: 1eceB
pdb bound state: Unbound
  compound: beta-D-Glucan
  pdb: 1vrxA
pdb bound state: Unbound
  compound: beta-D-Glucan
  pdb: 1vrxB
pdb bound state: Unbound
  compound: Peptidyl-Glu-cellulose
  pdb: 1c0dA
pdb bound state: Unbound
  compound: Peptidyl-Glu-cellulose
  pdb: 1c0dB
pdb bound state: Unbound
  compound: Peptidyl-Glu-cellulose
  pdb: 1eceA
pdb bound state: Unbound
  compound: Peptidyl-Glu-cellulose
  pdb: 1eceB
pdb bound state: Unbound
  compound: Peptidyl-Glu-cellulose
  pdb: 1vrxA
references: A common protein fold and similar active site in two distinct families of beta-glycanases.
references: Crystal structure of the catalytic domain of a bacterial cellulase belonging to family 5.
references: Crystal structure of thermostable family 5 endocellulase E1 from Acidothermus cellulolyticus in complex with cellotetraose.
references: The crystal structure of a family 5 endoglucanase mutant in complexed and uncomplexed forms reveals an induced fit activation mechanism.
references: Solution structure of the cellulose-binding domain of the endoglucanase Z secreted by Erwinia chrysanthemi.
references: Structure of the Bacillus agaradherans family 5 endoglucanase at 1.6 A and its cellobiose complex at 2.0 A resolution.
references: Snapshots along an enzymatic reaction coordinate: analysis of a retaining beta-glycoside hydrolase.
references: Insights into ligand-induced conformational change in Cel5A from Bacillus agaradhaerens revealed by a catalytically active crystal form.
references: Type II protein secretion in gram-negative pathogenic bacteria: the study of the structure/secretion relationships of the cellulase Cel5 (formerly EGZ) from Erwinia chrysanthemi.
references: A novel combination of two classic catalytic schemes.
references: Catalytically enhanced endocellulase Cel5A from Acidothermus cellulolyticus.
comment: This family belongs to glycosidase family-5, which has an retaining mechanism (equatorial to equatorial conformation), and also a family of 4/7 superfamily, which has got catalytic residues at the C-terminal ends of beta-4 and beta-7 on the (alpha/beta)8 barrel fold. This enzyme is composed of the N-terminal catalytic domain and the C-terminal Cellulose-binding domain. The structure of the C-terminal domain has not been determined yet. This enzyme must have the same catalytic mechanism as that of the other TIM barrel cellulases (S00203, D00501 & D00503 in EzCatDB). According to the literature [3], Glu282 and Glu162 (of 1ece) act as a nucleophile and acid-base, respectively. The catalysis proceeds through a dissociative-type (or SN1-like) mechanism, with a formation of oxocarbonium ion in the transition state, during the glycosylation of the active site. During the glycosylation, Glu282 approaches the C1 atom of the glcose, whilst Glu162 protonates the leaving group. At the second stage, or during the deglycosylation, a water molecule can be activated by a general base, Glu162. This deglycosylation also goes through the dissociative-type reaction with an oxocarbonium ion in the transition state, in which water replaced the glycosyl leaving group in the first step. Moreover, comparing the structural data with that of xylanase (E.C. 3.2.1.8) (D00479 in EzCatDB), Tyr240 (of 1ece) might stabilize the leaving nucleophile, Glu282 in deglycosylation, whilst His238 might modulate the activity of Glu162 (see [3]). On the other hand, Tyr240 might modulate the activity of the nucleophile, according to the data of the other homologous enzyme, beta-glucosidase (E.C. 3.2.1.21) (S00205 in EzCatDB).

TIM Barrel
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/3.20.20.80
catalytic domain: index.html

Immunoglobulin-like
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/2.60.40.290

Starch and sucrose metabolism
type: KeggPathway
references: KEGG:MAP00500

Cellulose
type: KeggSubstrate
references: KEGG:C00760
compound type: polysaccharide
type: KeggProduct

H2O
type: KeggSubstrate
references: KEGG:C00001
compound type: H2O
references: CHEBI:15377
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

Lichenin
type: KeggSubstrate
references: KEGG:C00478
compound type: carbohydrate
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

beta-D-Glucan
type: KeggSubstrate
references: KEGG:C00551
compound type: polysaccharide
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi
type: KeggProduct

Peptidyl-Glu-cellulose
type: KeggIntermediate
references: KEGG:I00120

1c0dA
type: Pdb
references: 1c0d
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1c0d
catalytic residue: ARG 62;ASN 161;GLU 162;HIS 238;TYR 240;GLU 282

1c0dB
type: Pdb
references: 1c0d
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1c0d
catalytic residue: ARG 62;ASN 161;GLU 162;HIS 238;TYR 240;GLU 282

1eceA
type: Pdb
references: 1ece
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1ece
catalytic residue: ARG 62;ASN 161;GLU 162;HIS 238;TYR 240;GLU 282

1eceB
type: Pdb
references: 1ece
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1ece
catalytic residue: ARG 62;ASN 161;GLU 162;HIS 238;TYR 240;GLU 282

1vrxA
type: Pdb
references: 1vrx
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1vrx
catalytic residue: ARG 62;ASN 161;GLU 162;HIS 238;TYR 240;GLU 282

1vrxB
type: Pdb
references: 1vrx
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1vrx
catalytic residue: ARG 62;ASN 161;GLU 162;HIS 238;TYR 240;GLU 282

A common protein fold and similar active site in two distinct families of beta-glycanases.
type: BibliographicResource
comment: X-ray crystallography (2.15 Angstroms)
medline id: 95393242
references: http://www.ncbi.nlm.nih.gov/pubmed/7664125
journal: Nat Struct Biol
volume: 2
pages: 569-76
published year: 1995
authors:
  item: Dominguez R
  item: Souchon H
  item: Spinelli S
  item: Dauter Z
  item: Wilson KS
  item: Chauvaux S
  item: Beguin P
  item: Alzari PM
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: P07985

Crystal structure of the catalytic domain of a bacterial cellulase belonging to family 5.
type: BibliographicResource
comment: X-ray crystallography (1.64 Angstroms) of 27-406
medline id: 96097400
references: http://www.ncbi.nlm.nih.gov/pubmed/8535787
journal: Structure
volume: 3
pages: 939-49
published year: 1995
authors:
  item: Ducros V
  item: Czjzek M
  item: Belaich A
  item: Gaudin C
  item: Fierobe HP
  item: Belaich JP
  item: Davies GJ
  item: Haser R
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: P17901

Crystal structure of thermostable family 5 endocellulase E1 from Acidothermus cellulolyticus in complex with cellotetraose.
type: BibliographicResource
comment: X-ray crystallography (2.4 Angstroms)
medline id: 96346058
references: http://www.ncbi.nlm.nih.gov/pubmed/8718854
journal: Biochemistry
volume: 35
pages: 10648-60
published year: 1996
authors:
  item: Sakon
  item: J.
  item: Adney
  item: W S.
  item: Himmel
  item: M E.
  item: Thomas
  item: S R.
  item: Karplus
  item: P A
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: P54583

The crystal structure of a family 5 endoglucanase mutant in complexed and uncomplexed forms reveals an induced fit activation mechanism.
type: BibliographicResource
comment: X-ray crystallography (2.3 Angstroms) of mutant GLN-140.
medline id: 96192088
references: http://www.ncbi.nlm.nih.gov/pubmed/8632467
journal: J Mol Biol
volume: 257
pages: 1042-51
published year: 1996
authors:
  item: Dominguez R
  item: Souchon H
  item: Lascombe M
  item: Alzari PM
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: P07985

Solution structure of the cellulose-binding domain of the endoglucanase Z secreted by Erwinia chrysanthemi.
type: BibliographicResource
comment: structure by NMR of 365-426
medline id: 98070232
references: http://www.ncbi.nlm.nih.gov/pubmed/9405041
journal: Biochemistry
volume: 36
pages: 16074-86
published year: 1997
authors:
  item: Brun E
  item: Moriaud F
  item: Gans P
  item: Blackledge MJ
  item: Barras F
  item: Marion D
references: P07103

Structure of the Bacillus agaradherans family 5 endoglucanase at 1.6 A and its cellobiose complex at 2.0 A resolution.
type: BibliographicResource
comment: X-ray crystallography (1.57 Angstroms) of 30-329
medline id: 98153671
references: http://www.ncbi.nlm.nih.gov/pubmed/9485319
journal: Biochemistry
volume: 37
pages: 1926-32
published year: 1998
authors:
  item: Davies GJ
  item: Dauter M
  item: Brzozowski AM
  item: Bjornvad ME
  item: Andersen KV
  item: Schulein M
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: O85465

Snapshots along an enzymatic reaction coordinate: analysis of a retaining beta-glycoside hydrolase.
type: BibliographicResource
comment: X-ray crystallography (1.64 Angstroms) of 30-329
medline id: 98384136
references: http://www.ncbi.nlm.nih.gov/pubmed/9718293
journal: Biochemistry
volume: 37
pages: 11707-13
published year: 1998
authors:
  item: Davies GJ
  item: Mackenzie L
  item: Varrot A
  item: Dauter M
  item: Brzozowski AM
  item: Schulein M
  item: Withers SG
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: O85465

Insights into ligand-induced conformational change in Cel5A from Bacillus agaradhaerens revealed by a catalytically active crystal form.
type: BibliographicResource
comment: X-ray crystallography (1.75/1.95/2.1 Angstroms)
references: http://www.ncbi.nlm.nih.gov/pubmed/10731432
journal: J Mol Biol
volume: 297
pages: 819-28
published year: 2000
authors:
  item: Varrot A
  item: Schulein M
  item: Davies GJ
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

Type II protein secretion in gram-negative pathogenic bacteria: the study of the structure/secretion relationships of the cellulase Cel5 (formerly EGZ) from Erwinia chrysanthemi.
type: BibliographicResource
comment: X-ray crystallography (2.3 Angstroms) of 44-335
medline id: 21392910
references: http://www.ncbi.nlm.nih.gov/pubmed/11501995
journal: J Mol Biol
volume: 310
pages: 1055-66
published year: 2001
authors:
  item: Chapon V
  item: Czjzek M
  item: El Hassouni M
  item: Py B
  item: Juy M
  item: Barras F
references: P07103

A novel combination of two classic catalytic schemes.
type: BibliographicResource
comment: X-ray crystallography, catalysis
references: http://www.ncbi.nlm.nih.gov/pubmed/12079387
journal: J Mol Biol
volume: 320
pages: 303-9
published year: 2002
authors:
  item: Shaw A
  item: Bott R
  item: Vonrhein C
  item: Bricogne G
  item: Power S
  item: Day AG

Catalytically enhanced endocellulase Cel5A from Acidothermus cellulolyticus.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/15917594
journal: Appl Biochem Biotechnol
volume: 121-124
pages: 129-48
published year: 2005
authors:
  item: Baker JO
  item: McCarley JR
  item: Lovett R
  item: Yu CH
  item: Adney WS
  item: Rignall TR
  item: Vinzant TB
  item: Decker SR
  item: Sakon J
  item: Himmel ME
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

ReferenceForCatalyticMechanism
reference index: 3
reference section: p.10656-10657, Fig.9
reference step: 4

ReferenceForCatalyticMechanism
reference index: 6
reference section: Fig.3
reference step: 4

ReferenceForCatalyticMechanism
reference index: 7
reference section: Fig.1, Fig.2
reference step: 4