D00431
type: Enzyme
rlcp: p10
cath: Thrombin, subunit H
ec: https://purl.uniprot.org/enzyme/3.4.21.59
uniprot: P20231
kegg enzyme: tryptase
kegg enzyme: mast cell tryptase
kegg enzyme: mast cell protease II
kegg enzyme: skin tryptase
kegg enzyme: lung tryptase
kegg enzyme: pituitary tryptase
kegg enzyme: mast cell neutral proteinase
kegg enzyme: mast cell serine proteinase II
kegg enzyme: mast cell proteinase II
kegg enzyme: mast cell serine proteinase tryptase
kegg enzyme: rat mast cell protease II
kegg enzyme: tryptase M
kegg substrate: Peptide
kegg substrate: Protein
kegg substrate: H2O
kegg product: Peptide
kegg product: Protein
kegg intermediate: Peptidyl-tetrahedral intermediate
kegg intermediate: Acyl-enzyme
kegg intermediate: Tetrahedral intermediate
pdb: 1a0lA01
pdb: 1a0lB01
pdb: 1a0lC01
pdb: 1a0lD01
pdb: 1a0lA02
pdb: 1a0lB02
pdb: 1a0lC02
pdb: 1a0lD02
pdb bound state: Unbound
  compound: Peptide
  pdb: 1a0lA01
pdb bound state: Unbound
  compound: Peptide
  pdb: 1a0lB01
pdb bound state: Unbound
  compound: Peptide
  pdb: 1a0lC01
pdb bound state: Unbound
  compound: Peptide
  pdb: 1a0lD01
pdb bound state: Unbound
  compound: Peptide
  pdb: 1a0lA02
pdb bound state: Unbound
  compound: Peptide
  pdb: 1a0lB02
pdb bound state: Unbound
  compound: Peptide
  pdb: 1a0lC02
pdb bound state: Unbound
  compound: Peptide
  pdb: 1a0lD02
pdb bound state: Unbound
  compound: Protein
  pdb: 1a0lA01
pdb bound state: Unbound
  compound: Protein
  pdb: 1a0lB01
pdb bound state: Unbound
  compound: Protein
  pdb: 1a0lC01
pdb bound state: Unbound
  compound: Protein
  pdb: 1a0lD01
pdb bound state: Unbound
  compound: Protein
  pdb: 1a0lA02
pdb bound state: Unbound
  compound: Protein
  pdb: 1a0lB02
pdb bound state: Unbound
  compound: Protein
  pdb: 1a0lC02
pdb bound state: Unbound
  compound: Protein
  pdb: 1a0lD02
pdb bound state: Unbound
  compound: Peptide
  pdb: 1a0lA01
pdb bound state: Unbound
  compound: Peptide
  pdb: 1a0lB01
pdb bound state: Unbound
  compound: Peptide
  pdb: 1a0lC01
pdb bound state: Unbound
  compound: Peptide
  pdb: 1a0lD01
pdb bound state: Unbound
  compound: Peptide
  pdb: 1a0lA02
pdb bound state: Unbound
  compound: Peptide
  pdb: 1a0lB02
pdb bound state: Unbound
  compound: Peptide
  pdb: 1a0lC02
pdb bound state: Unbound
  compound: Peptide
  pdb: 1a0lD02
active site residues resources: P20231
references: Bivalent inhibition of human beta-tryptase.
references: Selective inhibition of human mast cell tryptase by gabexate mesylate, an antiproteinase drug.
references: The 1.8 A crystal structure of human cathepsin G in complex with Suc-Val-Pro-PheP-(OPh)2: a Janus-faced proteinase with two opposite specificities.
references: The three-dimensional structure of recombinant leech-derived tryptase inhibitor in complex with trypsin. Implications for the structure of human mast cell tryptase and its inhibition.
references: Human tryptase fibrinogenolysis is optimal at acidic pH and generates anticoagulant fragments in the presence of the anti-tryptase monoclonal antibody B12.
references: Oxyanion-mediated inhibition of serine proteases.
references: Inhibitors of tryptase for the treatment of mast cell-mediated diseases.
references: Human beta-tryptase is a ring-like tetramer with active sites facing a central pore.
references: Bovine mast cell tryptase inactivation: effect of temperature.
references: Generation of catalytically active granzyme K from Escherichia coli inclusion bodies and identification of efficient granzyme K inhibitors in human plasma.
references: The structure of the human betaII-tryptase tetramer: fo(u)r better or worse.
references: Extrapancreatic trypsin-2 cleaves proteinase-activated receptor-2.
references: Granzymes (lymphocyte serine proteases): characterization with natural and synthetic substrates and inhibitors.
references: The human mast cell tryptase tetramer: a fascinating riddle solved by structure.
references: Formation of enzymatically active, homotypic, and heterotypic tetramers of mouse mast cell tryptases. Dependence on a conserved Trp-rich domain on the surface.
references: Mast cell tryptases and airway remodeling.
references: Human tryptase epsilon (PRSS22), a new member of the chromosome 16p13.3 family of human serine proteases expressed in airway epithelial cells.
references: Induction of rapid histone degradation by the cytotoxic T lymphocyte protease Granzyme A.
references: Diverse stability and catalytic properties of human tryptase alpha and beta isoforms are mediated by residue differences at the S1 pocket.
references: The crystal structure of human alpha1-tryptase reveals a blocked substrate-binding region.
references: Cyclotheonamide E4 and E5, new potent tryptase inhibitors from an Ircinia species of sponge.
comment: This enzyme belongs to the peptidase family-S1. According to the literature [6], this enzyme has got a similar catalytic triad (Ser/His/Asp) to that of trypsin, suggesting a similar mechanism.

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

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

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

Peptidyl-tetrahedral intermediate
type: KeggIntermediate
references: KEGG:I00087

Acyl-enzyme
type: KeggIntermediate
references: KEGG:I00085

Tetrahedral intermediate
type: KeggIntermediate
references: KEGG:I00086

1a0lA01
type: Pdb
references: 1a0l
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1a0l
catalytic residue: SER 195
main chain in catalysis: GLY 193;SER 195

1a0lB01
type: Pdb
references: 1a0l
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1a0l
catalytic residue: SER 195
main chain in catalysis: GLY 193;SER 195

1a0lC01
type: Pdb
references: 1a0l
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1a0l
catalytic residue: SER 195
main chain in catalysis: GLY 193;SER 195

1a0lD01
type: Pdb
references: 1a0l
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1a0l
catalytic residue: SER 195
main chain in catalysis: GLY 193;SER 195

1a0lA02
type: Pdb
references: 1a0l
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1a0l
catalytic residue: HIS 57;ASP 102

1a0lB02
type: Pdb
references: 1a0l
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1a0l
catalytic residue: HIS 57;ASP 102

1a0lC02
type: Pdb
references: 1a0l
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1a0l
catalytic residue: HIS 57;ASP 102

1a0lD02
type: Pdb
references: 1a0l
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1a0l
catalytic residue: HIS 57;ASP 102

Bivalent inhibition of human beta-tryptase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11325588
journal: Chem Biol
volume: 8
pages: 313-27
published year: 2001
authors:
  item: Schaschke N
  item: Matschiner G
  item: Zettl F
  item: Marquardt U
  item: Bergner A
  item: Bode W
  item: Sommerhoff CP
  item: Moroder L

Selective inhibition of human mast cell tryptase by gabexate mesylate, an antiproteinase drug.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11172730
journal: Biochem Pharmacol
volume: 61
pages: 271-6
published year: 2001
authors:
  item: Erba F
  item: Fiorucci L
  item: Pascarella S
  item: Menegatti E
  item: Ascenzi P
  item: Ascoli F

The 1.8 A crystal structure of human cathepsin G in complex with Suc-Val-Pro-PheP-(OPh)2: a Janus-faced proteinase with two opposite specificities.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/8896442
journal: EMBO J
volume: 15
pages: 5481-91
published year: 1996
authors:
  item: Hof P
  item: Mayr I
  item: Huber R
  item: Korzus E
  item: Potempa J
  item: Travis J
  item: Powers JC
  item: Bode W

The three-dimensional structure of recombinant leech-derived tryptase inhibitor in complex with trypsin. Implications for the structure of human mast cell tryptase and its inhibition.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9242660
journal: J Biol Chem
volume: 272
pages: 19931-7
published year: 1997
authors:
  item: Stubbs MT
  item: Morenweiser R
  item: Sturzebecher J
  item: Bauer M
  item: Bode W
  item: Huber R
  item: Piechottka GP
  item: Matschiner G
  item: Sommerhoff CP
  item: Fritz H
  item: Auerswald EA

Human tryptase fibrinogenolysis is optimal at acidic pH and generates anticoagulant fragments in the presence of the anti-tryptase monoclonal antibody B12.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9317153
journal: J Immunol
volume: 159
pages: 3540-8
published year: 1997
authors:
  item: Ren S
  item: Lawson AE
  item: Carr M
  item: Baumgarten CM
  item: Schwartz LB

Oxyanion-mediated inhibition of serine proteases.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9836602
journal: Biochemistry
volume: 37
pages: 17068-81
published year: 1998
authors:
  item: Presnell SR
  item: Patil GS
  item: Mura C
  item: Jude KM
  item: Conley JM
  item: Bertrand JA
  item: Kam CM
  item: Powers JC
  item: Williams LD

Inhibitors of tryptase for the treatment of mast cell-mediated diseases.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10197050
journal: Curr Pharm Des
volume: 4
pages: 381-96
published year: 1998
authors:
  item: Rice KD
  item: Tanaka RD
  item: Katz BA
  item: Numerof RP
  item: Moore WR

Human beta-tryptase is a ring-like tetramer with active sites facing a central pore.
type: BibliographicResource
comment: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS).
medline id: 98180625
references: http://www.ncbi.nlm.nih.gov/pubmed/9521329
journal: Nature
volume: 392
pages: 306-11
published year: 1998
authors:
  item: Pereira PJ
  item: Bergner A
  item: Macedo-Ribeiro S
  item: Huber R
  item: Matschiner G
  item: Fritz H
  item: Sommerhoff CP
  item: Bode W
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: P20231

Bovine mast cell tryptase inactivation: effect of temperature.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9533631
journal: Peptides
volume: 19
pages: 437-43
published year: 1998
authors:
  item: Erba F
  item: Fiorucci L
  item: Coletta M
  item: Ascoli F

Generation of catalytically active granzyme K from Escherichia coli inclusion bodies and identification of efficient granzyme K inhibitors in human plasma.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10480954
journal: J Biol Chem
volume: 274
pages: 27331-7
published year: 1999
authors:
  item: Wilharm E
  item: Parry MA
  item: Friebel R
  item: Tschesche H
  item: Matschiner G
  item: Sommerhoff CP
  item: Jenne DE

The structure of the human betaII-tryptase tetramer: fo(u)r better or worse.
type: BibliographicResource
comment: X-RAY CRYSTALLOGRAPHY (3.4 ANGSTROMS).
medline id: 99432168
references: http://www.ncbi.nlm.nih.gov/pubmed/10500112
journal: Proc Natl Acad Sci U S A
volume: 96
pages: 10984-91
published year: 1999
authors:
  item: Sommerhoff CP
  item: Bode W
  item: Pereira PJ
  item: Stubbs MT
  item: Sturzebecher J
  item: Piechottka GP
  item: Matschiner G
  item: Bergner A
references: P20231

Extrapancreatic trypsin-2 cleaves proteinase-activated receptor-2.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10944445
journal: Biochem Biophys Res Commun
volume: 275
pages: 77-83
published year: 2000
authors:
  item: Alm AK
  item: Gagnemo-Persson R
  item: Sorsa T
  item: Sundelin J

Granzymes (lymphocyte serine proteases): characterization with natural and synthetic substrates and inhibitors.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10708866
journal: Biochim Biophys Acta
volume: 1477
pages: 307-23
published year: 2000
authors:
  item: Kam CM
  item: Hudig D
  item: Powers JC

The human mast cell tryptase tetramer: a fascinating riddle solved by structure.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10708850
journal: Biochim Biophys Acta
volume: 1477
pages: 75-89
published year: 2000
authors:
  item: Sommerhoff CP
  item: Bode W
  item: Matschiner G
  item: Bergner A
  item: Fritz H

Formation of enzymatically active, homotypic, and heterotypic tetramers of mouse mast cell tryptases. Dependence on a conserved Trp-rich domain on the surface.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10617625
journal: J Biol Chem
volume: 275
pages: 351-8
published year: 2000
authors:
  item: Huang C
  item: Morales G
  item: Vagi A
  item: Chanasyk K
  item: Ferrazzi M
  item: Burklow C
  item: Qiu WT
  item: Feyfant E
  item: Sali A
  item: Stevens RL

Mast cell tryptases and airway remodeling.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11734467
journal: Am J Respir Crit Care Med
volume: 164
pages: S52-8
published year: 2001
authors:
  item: Sommerhoff CP

Human tryptase epsilon (PRSS22), a new member of the chromosome 16p13.3 family of human serine proteases expressed in airway epithelial cells.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11602603
journal: J Biol Chem
volume: 276
pages: 49169-82
published year: 2001
authors:
  item: Wong GW
  item: Yasuda S
  item: Madhusudhan MS
  item: Li L
  item: Yang Y
  item: Krilis SA
  item: Sali A
  item: Stevens RL

Induction of rapid histone degradation by the cytotoxic T lymphocyte protease Granzyme A.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11060286
journal: J Biol Chem
volume: 276
pages: 3683-90
published year: 2001
authors:
  item: Zhang D
  item: Pasternack MS
  item: Beresford PJ
  item: Wagner L
  item: Greenberg AH
  item: Lieberman J

Diverse stability and catalytic properties of human tryptase alpha and beta isoforms are mediated by residue differences at the S1 pocket.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11876641
journal: Biochemistry
volume: 41
pages: 3329-40
published year: 2002
authors:
  item: Selwood T
  item: Wang ZM
  item: McCaslin DR
  item: Schechter NM

The crystal structure of human alpha1-tryptase reveals a blocked substrate-binding region.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/12162961
journal: J Mol Biol
volume: 321
pages: 491-502
published year: 2002
authors:
  item: Marquardt U
  item: Zettl F
  item: Huber R
  item: Bode W
  item: Sommerhoff C

Cyclotheonamide E4 and E5, new potent tryptase inhibitors from an Ircinia species of sponge.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11908961
journal: J Nat Prod
volume: 65
pages: 259-61
published year: 2002
authors:
  item: Murakami Y
  item: Takei M
  item: Shindo K
  item: Kitazume C
  item: Tanaka J
  item: Higa T
  item: Fukamachi H

IntermediateAnalogue
compound: Peptidyl-tetrahedral intermediate
pdb: 1a0lA01
ligand het code: APA

IntermediateAnalogue
compound: Peptidyl-tetrahedral intermediate
pdb: 1a0lB01
ligand het code: APA

IntermediateAnalogue
compound: Peptidyl-tetrahedral intermediate
pdb: 1a0lC01
ligand het code: APA

IntermediateAnalogue
compound: Peptidyl-tetrahedral intermediate
pdb: 1a0lD01
ligand het code: APA

ReferenceForCatalyticMechanism
reference index: 4
reference section: p.17079

ReferenceForCatalyticMechanism
reference index: 6
reference section: p.309