D00855
type: Enzyme
rlcp: p10
cath: Thrombin, subunit H
ec: https://purl.uniprot.org/enzyme/3.4.21.79
uniprot: P18291
uniprot: P10144
kegg enzyme: Granzyme B
kegg enzyme: CTLA1
kegg enzyme: CCPII
kegg enzyme: Cytotoxic cell proteinase-1
kegg enzyme: Granzyme G
kegg enzyme: Granzyme H
kegg enzyme: CCP1 proteinase
kegg substrate: Protein
kegg substrate: H2O
kegg product: Protein
kegg product: Peptide
kegg intermediate: Peptidyl-Ser-tetrahedral-intermediate (with previous peptide)
kegg intermediate: Acyl-enzyme(Peptidyl-Ser-acyl group)
kegg intermediate: Peptidyl-Ser-tetrahedral-intermediate
pdb: 1fi8A01
pdb: 1fi8B01
pdb: 1fq3A01
pdb: 1fq3B01
pdb: 1iauA01
pdb: 1fi8A02
pdb: 1fi8B02
pdb: 1fq3A02
pdb: 1fq3B02
pdb: 1iauA02
pdb bound state: Unbound
  compound: Protein
  pdb: 1fi8A01
pdb bound state: Unbound
  compound: Protein
  pdb: 1fi8B01
pdb bound state: Unbound
  compound: Protein
  pdb: 1fq3A01
pdb bound state: Unbound
  compound: Protein
  pdb: 1fq3B01
pdb bound state: Unbound
  compound: Protein
  pdb: 1iauA01
pdb bound state: Unbound
  compound: Protein
  pdb: 1fi8A02
pdb bound state: Unbound
  compound: Protein
  pdb: 1fi8B02
pdb bound state: Unbound
  compound: Protein
  pdb: 1fq3A02
pdb bound state: Unbound
  compound: Protein
  pdb: 1fq3B02
pdb bound state: Unbound
  compound: Protein
  pdb: 1iauA02
pdb bound state: Unbound
  compound: Protein
  pdb: 1fi8A01
pdb bound state: Unbound
  compound: Protein
  pdb: 1fi8B01
pdb bound state: Unbound
  compound: Protein
  pdb: 1fq3A01
pdb bound state: Unbound
  compound: Protein
  pdb: 1fq3B01
pdb bound state: Unbound
  compound: Protein
  pdb: 1iauA01
pdb bound state: Unbound
  compound: Protein
  pdb: 1fi8A02
pdb bound state: Unbound
  compound: Protein
  pdb: 1fi8B02
pdb bound state: Unbound
  compound: Protein
  pdb: 1fq3A02
pdb bound state: Unbound
  compound: Protein
  pdb: 1fq3B02
pdb bound state: Unbound
  compound: Protein
  pdb: 1iauA02
pdb bound state: Analogue
  compound: Peptide
  pdb: 1fi8A01
  ligand het code: PRO_83-ASP_84(chain C)
pdb bound state: Analogue
  compound: Peptide
  pdb: 1fi8B01
  ligand het code: PRO_83-ASP_84(chain E)
pdb bound state: Unbound
  compound: Peptide
  pdb: 1fq3A01
pdb bound state: Unbound
  compound: Peptide
  pdb: 1fq3B01
pdb bound state: Unbound
  compound: Peptide
  pdb: 1iauA01
pdb bound state: Unbound
  compound: Peptide
  pdb: 1fi8A02
pdb bound state: Unbound
  compound: Peptide
  pdb: 1fi8B02
pdb bound state: Unbound
  compound: Peptide
  pdb: 1fq3A02
pdb bound state: Unbound
  compound: Peptide
  pdb: 1fq3B02
pdb bound state: Unbound
  compound: Peptide
  pdb: 1iauA02
pdb bound state: Unbound
  compound: Peptidyl-Ser-tetrahedral-intermediate (with previous peptide)
  pdb: 1fi8A01
pdb bound state: Unbound
  compound: Peptidyl-Ser-tetrahedral-intermediate (with previous peptide)
  pdb: 1fi8B01
pdb bound state: Unbound
  compound: Peptidyl-Ser-tetrahedral-intermediate (with previous peptide)
  pdb: 1fq3A01
pdb bound state: Unbound
  compound: Peptidyl-Ser-tetrahedral-intermediate (with previous peptide)
  pdb: 1fq3B01
pdb bound state: Unbound
  compound: Peptidyl-Ser-tetrahedral-intermediate (with previous peptide)
  pdb: 1iauA01
active site residues resources: The structure of the pro-apoptotic protease granzyme B reveals the molecular determinants of its specificity.
active site residues resources: Serine protease mechanism and specificity.
active site residues resources: P10144
active site residues resources: P18291
references: A combinatorial approach defines specificities of members of the caspase family and granzyme B. Functional relationships established for key mediators of apoptosis.
references: Definition and redesign of the extended substrate specificity of granzyme B.
references: Crystal structure of the caspase activator human granzyme B, a proteinase highly specific for an Asp-P1 residue.
references: The structure of the pro-apoptotic protease granzyme B reveals the molecular determinants of its specificity.
references: The three-dimensional structure of human granzyme B compared to caspase-3, key mediators of cell death with cleavage specificity for aspartic acid in P1.
references: Serine protease mechanism and specificity.
references: Mechanisms of granule-dependent killing.
references: Analysis of protein processing by N-terminal proteomics reveals novel species-specific substrate determinants of granzyme B orthologs.
references: Cytotoxic and non-cytotoxic roles of the CTL/NK protease granzyme B.
references: Granzyme B-induced apoptosis in cancer cells and its regulation (review).
comment: This enzyme belongs to peptidase family-S1. This enzyme seems to activate caspases, and is involved in apoptosis in cancer cells (see [7], [9], [10]). Since this enzyme has got the same catalytic site as trypsin, it must catalyze the trypsin-like reaction.

Thrombin, subunit H
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/2.40.10.10
catalytic domain: index.html

Protein
type: KeggSubstrate
references: KEGG:C00017
compound type: peptide/protein
type: KeggProduct

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

Peptide
type: KeggProduct
references: KEGG:C00012
compound type: peptide/protein

Peptidyl-Ser-tetrahedral-intermediate (with previous peptide)
type: KeggIntermediate
references: KEGG:I00087

Acyl-enzyme(Peptidyl-Ser-acyl group)
type: KeggIntermediate
references: KEGG:I00085

Peptidyl-Ser-tetrahedral-intermediate
type: KeggIntermediate
references: KEGG:I00086

1fi8A01
type: Pdb
references: 1fi8
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1fi8
catalytic residue: SER 195
main chain in catalysis: GLY 193;SER 195

1fi8B01
type: Pdb
references: 1fi8
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1fi8
catalytic residue: SER 195
main chain in catalysis: GLY 193;SER 195

1fq3A01
type: Pdb
references: 1fq3
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1fq3
catalytic residue: SER 195
main chain in catalysis: GLY 193;SER 195

1fq3B01
type: Pdb
references: 1fq3
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1fq3
catalytic residue: SER 195
main chain in catalysis: GLY 193;SER 195

1iauA01
type: Pdb
references: 1iau
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1iau
catalytic residue: SER 195
main chain in catalysis: GLY 193;SER 195

1fi8A02
type: Pdb
references: 1fi8
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1fi8
catalytic residue: HIS 57;ASP 102

1fi8B02
type: Pdb
references: 1fi8
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1fi8
catalytic residue: HIS 57;ASP 102

1fq3A02
type: Pdb
references: 1fq3
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1fq3
catalytic residue: HIS 57;ASP 102

1fq3B02
type: Pdb
references: 1fq3
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1fq3
catalytic residue: HIS 57;ASP 102

1iauA02
type: Pdb
references: 1iau
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1iau
catalytic residue: HIS 57;ASP 102

A combinatorial approach defines specificities of members of the caspase family and granzyme B. Functional relationships established for key mediators of apoptosis.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9218414
journal: J Biol Chem
volume: 272
pages: 17907-11
published year: 1997
authors:
  item: Thornberry NA
  item: Rano TA
  item: Peterson EP
  item: Rasper DM
  item: Timkey T
  item: Garcia-Calvo M
  item: Houtzager VM
  item: Nordstrom PA
  item: Roy S
  item: Vaillancourt JP
  item: Chapman KT
  item: Nicholson DW

Definition and redesign of the extended substrate specificity of granzyme B.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9765264
journal: J Biol Chem
volume: 273
pages: 27364-73
published year: 1998
authors:
  item: Harris JL
  item: Peterson EP
  item: Hudig D
  item: Thornberry NA
  item: Craik CS

Crystal structure of the caspase activator human granzyme B, a proteinase highly specific for an Asp-P1 residue.
type: BibliographicResource
comment: X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 21-247.
references: http://www.ncbi.nlm.nih.gov/pubmed/11209755
journal: Biol Chem
volume: 381
pages: 1203-14
published year: 2000
authors:
  item: Estebanez-Perpina E
  item: Fuentes-Prior P
  item: Belorgey D
  item: Braun M
  item: Kiefersauer R
  item: Maskos K
  item: Huber R
  item: Rubin H
  item: Bode W
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: P10144

The structure of the pro-apoptotic protease granzyme B reveals the molecular determinants of its specificity.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10966646
journal: Nat Struct Biol
volume: 7
pages: 762-5
published year: 2000
authors:
  item: Waugh SM
  item: Harris JL
  item: Fletterick R
  item: Craik CS
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: P18291

The three-dimensional structure of human granzyme B compared to caspase-3, key mediators of cell death with cleavage specificity for aspartic acid in P1.
type: BibliographicResource
comment: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 21-247.
references: http://www.ncbi.nlm.nih.gov/pubmed/11325591
journal: Chem Biol
volume: 8
pages: 357-68
published year: 2001
authors:
  item: Rotonda J
  item: Garcia-Calvo M
  item: Bull HG
  item: Geissler WM
  item: McKeever BM
  item: Willoughby CA
  item: Thornberry NA
  item: Becker JW
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: P10144

Serine protease mechanism and specificity.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/12475199
journal: Chem Rev
volume: 102
pages: 4501-24
published year: 2002
authors:
  item: Hedstrom L

Mechanisms of granule-dependent killing.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/17975553
journal: Cell Death Differ
volume: 15
pages: 251-62
published year: 2008
authors:
  item: Cullen SP
  item: Martin SJ

Analysis of protein processing by N-terminal proteomics reveals novel species-specific substrate determinants of granzyme B orthologs.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/18836177
journal: Mol Cell Proteomics
volume: 8
pages: 258-72
published year: 2009
authors:
  item: Van Damme P
  item: Maurer-Stroh S
  item: Plasman K
  item: Van Durme J
  item: Colaert N
  item: Timmerman E
  item: De Bock PJ
  item: Goethals M
  item: Rousseau F
  item: Schymkowitz J
  item: Vandekerckhove J
  item: Gevaert K

Cytotoxic and non-cytotoxic roles of the CTL/NK protease granzyme B.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/20536558
journal: Immunol Rev
volume: 235
pages: 105-16
published year: 2010
authors:
  item: Afonina IS
  item: Cullen SP
  item: Martin SJ

Granzyme B-induced apoptosis in cancer cells and its regulation (review).
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/21042704
journal: Int J Oncol
volume: 37
pages: 1361-78
published year: 2010
authors:
  item: Rousalova I
  item: Krepela E

TransitionStateAnalogue
compound: Peptidyl-Ser-tetrahedral-intermediate
pdb: 1iauA01
ligand het code: ACE-ILE-GLU-PRO-ASA

ReferenceForCatalyticMechanism
reference index: 6
reference section: Figure 5