D00426
type: Enzyme
rlcp: p10
cath: Thrombin, subunit H
ec: https://purl.uniprot.org/enzyme/3.4.21.20
uniprot: P08311
kegg enzyme: cathepsin G
kegg enzyme: chymotrypsin-like proteinase
kegg enzyme: neutral proteinase
kegg substrate: Protein
kegg substrate: Peptide
kegg substrate: H2O
kegg product: Oligopeptide
kegg product: Peptide
kegg intermediate: Peptidyl-tetrahedral intermediate
kegg intermediate: Acyl-enzyme
kegg intermediate: Tetrahedral intermediate
pdb: 1au8A01
pdb: 1cghA01
pdb: 1kynA01
pdb: 1kynB01
pdb: 1au8A02
pdb: 1cghA02
pdb: 1kynA02
pdb: 1kynB02
pdb bound state: Unbound
  compound: Protein
  pdb: 1au8A01
pdb bound state: Unbound
  compound: Protein
  pdb: 1cghA01
pdb bound state: Unbound
  compound: Protein
  pdb: 1kynA01
pdb bound state: Unbound
  compound: Protein
  pdb: 1kynB01
pdb bound state: Unbound
  compound: Protein
  pdb: 1au8A02
pdb bound state: Unbound
  compound: Protein
  pdb: 1cghA02
pdb bound state: Unbound
  compound: Protein
  pdb: 1kynA02
pdb bound state: Unbound
  compound: Protein
  pdb: 1kynB02
pdb bound state: Unbound
  compound: Peptide
  pdb: 1au8A01
pdb bound state: Unbound
  compound: Peptide
  pdb: 1cghA01
pdb bound state: Unbound
  compound: Peptide
  pdb: 1kynA01
pdb bound state: Unbound
  compound: Peptide
  pdb: 1kynB01
pdb bound state: Unbound
  compound: Peptide
  pdb: 1au8A02
pdb bound state: Unbound
  compound: Peptide
  pdb: 1cghA02
pdb bound state: Unbound
  compound: Peptide
  pdb: 1kynA02
pdb bound state: Unbound
  compound: Peptide
  pdb: 1kynB02
pdb bound state: Unbound
  compound: Oligopeptide
  pdb: 1au8A01
pdb bound state: Unbound
  compound: Oligopeptide
  pdb: 1cghA01
pdb bound state: Unbound
  compound: Oligopeptide
  pdb: 1kynA01
pdb bound state: Unbound
  compound: Oligopeptide
  pdb: 1kynB01
pdb bound state: Unbound
  compound: Oligopeptide
  pdb: 1au8A02
pdb bound state: Unbound
  compound: Oligopeptide
  pdb: 1cghA02
pdb bound state: Unbound
  compound: Oligopeptide
  pdb: 1kynA02
pdb bound state: Unbound
  compound: Oligopeptide
  pdb: 1kynB02
pdb bound state: Unbound
  compound: Peptide
  pdb: 1au8A01
pdb bound state: Unbound
  compound: Peptide
  pdb: 1cghA01
pdb bound state: Unbound
  compound: Peptide
  pdb: 1kynA01
pdb bound state: Unbound
  compound: Peptide
  pdb: 1kynB01
pdb bound state: Unbound
  compound: Peptide
  pdb: 1au8A02
active site residues resources: P08311
active site residues resources: 1au8
references: Inhibition of cathepsin G by 4H-3,1-benzoxazin-4-ones.
references: Neutrophil elastase and cathepsin G: structure, function, and biological control.
references: Nonchromogenic hydrolysis of elastase and cathepsin G p-nitroanilide substrates by Pseudomonas aeruginosa elastase.
references: Ionic inhibitors of human leukocyte elastase: pyridinium and phenyl carboxylate derivatives of 3-alkyl-N-hydroxysuccinimide.
references: Irreversible inhibition of serine proteases by peptide derivatives of (alpha-aminoalkyl)phosphonate diphenyl esters.
references: Insight into the nature and site of oxygen-centered free radical generation by endothelial cell monolayers using a novel spin trapping technique.
references: Defibrotide inhibits platelet activation by cathepsin G released from stimulated polymorphonuclear leukocytes.
references: The isoforms of human neutrophil elastase and cathepsin G differ in their carbohydrate side chain structures.
references: Cathepsin G inactivates human protein S in vitro.
references: Mechanism-based inhibition of human leukocyte elastase and cathepsin G by substituted dihydrouracils.
references: Interleukin-8 processing by neutrophil elastase, cathepsin G and proteinase-3.
references: http://ezcatdb.cbrc.jp/EzCatDB/reference/D00426#11
references: Isoxazoline derivatives as potential inhibitors of the proteolytic enzymes human leukocyte elastase, cathepsin G and proteinase 3: a structure-activity relationship study.
references: Design, synthesis, and in vitro inhibitory activity toward human leukocyte elastase, cathepsin G, and proteinase 3 of saccharin-derived sulfones and congeners.
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: Structure-based design of a general class of mechanism-based inhibitors of the serine proteinases employing a novel amino acid-derived heterocyclic scaffold.
references: Inhibition of human immunodeficiency virus type 1 infectivity by secretory leukocyte protease inhibitor occurs prior to viral reverse transcription.
references: Proteolysis of factor V by cathepsin G and elastase indicates that cleavage at Arg1545 optimizes cofactor function by facilitating factor Xa binding.
references: Angiotensin II generation at the cell surface of activated neutrophils: novel cathepsin G-mediated catalytic activity that is resistant to inhibition.
references: New, sensitive fluorogenic substrates for human cathepsin G based on the sequence of serpin-reactive site loops.
references: Enzymatic and molecular biochemical characterizations of human neutrophil elastases and a cathepsin G-like enzyme.
references: NMR solution structure of Apis mellifera chymotrypsin/cathepsin G inhibitor-1 (AMCI-1): structural similarity with Ascaris protease inhibitors.
references: Characterization of the necrotic cleavage of poly(ADP-ribose) polymerase (PARP-1): implication of lysosomal proteases.
references: Nonpeptide inhibitors of cathepsin G: optimization of a novel beta-ketophosphonic acid lead by structure-based drug design.
comment: This enzyme belongs to the peptidase family-S1. According to the literature [14], this enzyme has got a similar catalytic triad (Ser/His/Asp) and an oxyanion hole, 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

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

Peptide
type: KeggSubstrate
references: KEGG:C00012
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

Oligopeptide
type: KeggProduct
references: KEGG:C00098
compound type: amine group
compound type: carboxyl group
compound type: peptide/protein

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

Acyl-enzyme
type: KeggIntermediate
references: KEGG:I00085

Tetrahedral intermediate
type: KeggIntermediate
references: KEGG:I00086

1au8A01
type: Pdb
references: 1au8
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1au8
catalytic residue: SER 195
main chain in catalysis: GLY 193;SER 195

1cghA01
type: Pdb
references: 1cgh
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1cgh
catalytic residue: SER 195
main chain in catalysis: GLY 193;SER 195

1kynA01
type: Pdb
references: 1kyn
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1kyn
catalytic residue: SER 195
main chain in catalysis: GLY 193;SER 195

1kynB01
type: Pdb
references: 1kyn
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1kyn
catalytic residue: SER 495
main chain in catalysis: GLY 493;SER 495

1au8A02
type: Pdb
references: 1au8
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1au8
catalytic residue: HIS 57;ASP 102

1cghA02
type: Pdb
references: 1cgh
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1cgh
catalytic residue: HIS 57;ASP 102

1kynA02
type: Pdb
references: 1kyn
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1kyn
catalytic residue: HIS 57;ASP 102

1kynB02
type: Pdb
references: 1kyn
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1kyn
catalytic residue: HIS 357;ASP 402

Inhibition of cathepsin G by 4H-3,1-benzoxazin-4-ones.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9370038
journal: Bioorg Med Chem
volume: 5
pages: 1935-42
published year: 1997
authors:
  item: Gutschow M
  item: Neumann U

Neutrophil elastase and cathepsin G: structure, function, and biological control.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/3266707
journal: Adv Exp Med Biol
volume: 240
pages: 23-31
published year: 1988
authors:
  item: Watorek W
  item: Farley D
  item: Salvesen G
  item: Travis J

Nonchromogenic hydrolysis of elastase and cathepsin G p-nitroanilide substrates by Pseudomonas aeruginosa elastase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/2516450
journal: Am J Respir Cell Mol Biol
volume: 1
pages: 37-9
published year: 1989
authors:
  item: Pelletier A
  item: Dimicoli JL
  item: Boudier C
  item: Bieth JG

Ionic inhibitors of human leukocyte elastase: pyridinium and phenyl carboxylate derivatives of 3-alkyl-N-hydroxysuccinimide.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/2280356
journal: J Pharm Sci
volume: 79
pages: 886-8
published year: 1990
authors:
  item: Groutas WC
  item: Stanga MA
  item: Castrisos JC
  item: Schatz EJ
  item: Brubaker MJ

Irreversible inhibition of serine proteases by peptide derivatives of (alpha-aminoalkyl)phosphonate diphenyl esters.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/1988040
journal: Biochemistry
volume: 30
pages: 485-93
published year: 1991
authors:
  item: Oleksyszyn J
  item: Powers JC

Insight into the nature and site of oxygen-centered free radical generation by endothelial cell monolayers using a novel spin trapping technique.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/1310061
journal: Blood
volume: 79
pages: 699-707
published year: 1992
authors:
  item: Britigan BE
  item: Roeder TL
  item: Shasby DM

Defibrotide inhibits platelet activation by cathepsin G released from stimulated polymorphonuclear leukocytes.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/1509406
journal: Thromb Haemost
volume: 67
pages: 660-4
published year: 1992
authors:
  item: Evangelista V
  item: Piccardoni P
  item: de Gaetano G
  item: Cerletti C

The isoforms of human neutrophil elastase and cathepsin G differ in their carbohydrate side chain structures.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/8357534
journal: Biol Chem Hoppe Seyler
volume: 374
pages: 385-93
published year: 1993
authors:
  item: Watorek W
  item: van Halbeek H
  item: Travis J

Cathepsin G inactivates human protein S in vitro.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/8365692
journal: Haemostasis
volume: 23
pages: 98-103
published year: 1993
authors:
  item: Turkington PT

Mechanism-based inhibition of human leukocyte elastase and cathepsin G by substituted dihydrouracils.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/7986820
journal: Biochim Biophys Acta
volume: 1227
pages: 130-6
published year: 1994
authors:
  item: Groutas WC
  item: Huang H
  item: Epp JB
  item: Venkataraman R
  item: McClenahan JJ
  item: Tagusagawa F

Interleukin-8 processing by neutrophil elastase, cathepsin G and proteinase-3.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/7925979
journal: FEBS Lett
volume: 352
pages: 231-5
published year: 1994
authors:
  item: Padrines M
  item: Wolf M
  item: Walz A
  item: Baggiolini M

http://ezcatdb.cbrc.jp/EzCatDB/reference/D00426#11
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/7796053
journal: Bioorg Med Chem
volume: 3
pages: 187-93
published year: 1995
authors:
  item: Groutas WC
  item: Chong LS
  item: Venkataraman R
  item: Epp JB
  item: Kuang R
  item: Houser-Archield N
  item: Hoidal JR
title: The Gabriel-Colman rearrangement in biological systems: design, synthesis and biological evaluation of phthalimide and saccharin derivatives as potential mechanism-based inhibitors of human leukocyte elastase, cathepsin G and proteinase 3.

Isoxazoline derivatives as potential inhibitors of the proteolytic enzymes human leukocyte elastase, cathepsin G and proteinase 3: a structure-activity relationship study.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/7796046
journal: Bioorg Med Chem
volume: 3
pages: 125-8
published year: 1995
authors:
  item: Groutas WC
  item: Venkataraman R
  item: Chong LS
  item: Yoder JE
  item: Epp JB
  item: Stanga MA
  item: Kim EH

Design, synthesis, and in vitro inhibitory activity toward human leukocyte elastase, cathepsin G, and proteinase 3 of saccharin-derived sulfones and congeners.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/8894097
journal: Bioorg Med Chem
volume: 4
pages: 1393-400
published year: 1996
authors:
  item: Groutas WC
  item: Epp JB
  item: Venkataraman R
  item: Kuang R
  item: Truong TM
  item: McClenahan JJ
  item: Prakash O

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
comment: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
medline id: 97051807
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
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: P08311

Structure-based design of a general class of mechanism-based inhibitors of the serine proteinases employing a novel amino acid-derived heterocyclic scaffold.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9125494
journal: Biochemistry
volume: 36
pages: 4739-50
published year: 1997
authors:
  item: Groutas WC
  item: Kuang R
  item: Venkataraman R
  item: Epp JB
  item: Ruan S
  item: Prakash O

Inhibition of human immunodeficiency virus type 1 infectivity by secretory leukocyte protease inhibitor occurs prior to viral reverse transcription.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9242546
journal: Blood
volume: 90
pages: 1141-9
published year: 1997
authors:
  item: McNeely TB
  item: Shugars DC
  item: Rosendahl M
  item: Tucker C
  item: Eisenberg SP
  item: Wahl SM

Proteolysis of factor V by cathepsin G and elastase indicates that cleavage at Arg1545 optimizes cofactor function by facilitating factor Xa binding.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9718313
journal: Biochemistry
volume: 37
pages: 11896-906
published year: 1998
authors:
  item: Camire RM
  item: Kalafatis M
  item: Tracy PB

Angiotensin II generation at the cell surface of activated neutrophils: novel cathepsin G-mediated catalytic activity that is resistant to inhibition.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9570564
journal: J Immunol
volume: 160
pages: 1436-43
published year: 1998
authors:
  item: Owen CA
  item: Campbell EJ

New, sensitive fluorogenic substrates for human cathepsin G based on the sequence of serpin-reactive site loops.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10318785
journal: J Biol Chem
volume: 274
pages: 13810-7
published year: 1999
authors:
  item: Rehault S
  item: Brillard-Bourdet M
  item: Juliano MA
  item: Juliano L
  item: Gauthier F
  item: Moreau T

Enzymatic and molecular biochemical characterizations of human neutrophil elastases and a cathepsin G-like enzyme.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11101139
journal: Mol Cells
volume: 10
pages: 498-504
published year: 2000
authors:
  item: Kim WM
  item: Kang K

NMR solution structure of Apis mellifera chymotrypsin/cathepsin G inhibitor-1 (AMCI-1): structural similarity with Ascaris protease inhibitors.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10850807
journal: Protein Sci
volume: 9
pages: 976-84
published year: 2000
authors:
  item: Cierpicki T
  item: Bania J
  item: Otlewski J

Characterization of the necrotic cleavage of poly(ADP-ribose) polymerase (PARP-1): implication of lysosomal proteases.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11536009
journal: Cell Death Differ
volume: 8
pages: 588-94
published year: 2001
authors:
  item: Gobeil S
  item: Boucher CC
  item: Nadeau D
  item: Poirier GG

Nonpeptide inhibitors of cathepsin G: optimization of a novel beta-ketophosphonic acid lead by structure-based drug design.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11942800
journal: J Am Chem Soc
volume: 124
pages: 3810-1
published year: 2002
authors:
  item: Greco MN
  item: Hawkins MJ
  item: Powell ET
  item: Almond HR Jr
  item: Corcoran TW
  item: de Garavilla L
  item: Kauffman JA
  item: Recacha R
  item: Chattopadhyay D
  item: Andrade-Gordon P
  item: Maryanoff BE
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

IntermediateAnalogue
compound: Tetrahedral intermediate
pdb: 1au8A01
ligand het code: SIN-VAL-PRO-KPH (chain S)

IntermediateAnalogue
compound: Tetrahedral intermediate
pdb: 1cghA01
ligand het code: SIN-VAL-PRO-PPH (chain S)

ReferenceForCatalyticMechanism
reference index: 14
reference section: p.5485-5486