S00451
type: Enzyme
rlcp: p44
cath: Cathepsin B; Chain A
ec: https://purl.uniprot.org/enzyme/3.4.22.38
uniprot: P43235
kegg enzyme: cathepsin K
kegg enzyme: cathepsin O and cathepsin X (both misleading, having been used forother enzymes)
kegg enzyme: cathepsin O2
kegg substrate: Fibrinogen
kegg substrate: H2O
kegg product: Protein
kegg product: Peptide
pdb: 1atkA
pdb: 1au0A
pdb: 1au2A
pdb: 1au3A
pdb: 1au4A
pdb: 1ayuA
pdb: 1ayvA
pdb: 1aywA
pdb: 1bgoA
pdb: 1by8A
pdb: 1memA
pdb bound state: Unbound
  compound: Fibrinogen
  pdb: 1atkA
pdb bound state: Unbound
  compound: Fibrinogen
  pdb: 1au0A
pdb bound state: Unbound
  compound: Fibrinogen
  pdb: 1au2A
pdb bound state: Unbound
  compound: Fibrinogen
  pdb: 1au3A
pdb bound state: Unbound
  compound: Fibrinogen
  pdb: 1au4A
pdb bound state: Unbound
  compound: Fibrinogen
  pdb: 1ayuA
pdb bound state: Unbound
  compound: Fibrinogen
  pdb: 1ayvA
pdb bound state: Unbound
  compound: Fibrinogen
  pdb: 1aywA
pdb bound state: Unbound
  compound: Fibrinogen
  pdb: 1bgoA
pdb bound state: Unbound
  compound: Fibrinogen
  pdb: 1by8A
pdb bound state: Unbound
  compound: Fibrinogen
  pdb: 1memA
pdb bound state: Unbound
  compound: Protein
  pdb: 1atkA
pdb bound state: Unbound
  compound: Protein
  pdb: 1au0A
pdb bound state: Unbound
  compound: Protein
  pdb: 1au2A
pdb bound state: Unbound
  compound: Protein
  pdb: 1au3A
pdb bound state: Unbound
  compound: Protein
  pdb: 1au4A
pdb bound state: Unbound
  compound: Protein
  pdb: 1ayuA
pdb bound state: Unbound
  compound: Protein
  pdb: 1ayvA
pdb bound state: Unbound
  compound: Protein
  pdb: 1aywA
pdb bound state: Unbound
  compound: Protein
  pdb: 1bgoA
pdb bound state: Unbound
  compound: Protein
  pdb: 1by8A
pdb bound state: Unbound
  compound: Protein
  pdb: 1memA
pdb bound state: Unbound
  compound: Peptide
  pdb: 1atkA
pdb bound state: Unbound
  compound: Peptide
  pdb: 1au0A
pdb bound state: Unbound
  compound: Peptide
  pdb: 1au2A
pdb bound state: Unbound
  compound: Peptide
  pdb: 1au3A
pdb bound state: Unbound
  compound: Peptide
  pdb: 1au4A
pdb bound state: Unbound
  compound: Peptide
  pdb: 1ayuA
pdb bound state: Unbound
  compound: Peptide
  pdb: 1ayvA
pdb bound state: Unbound
  compound: Peptide
  pdb: 1aywA
pdb bound state: Unbound
  compound: Peptide
  pdb: 1bgoA
pdb bound state: Unbound
  compound: Peptide
  pdb: 1by8A
pdb bound state: Unbound
  compound: Peptide
  pdb: 1memA
pdb bound state: IntermediateAnalogue
  pdb: 1atkA
  ligand het code: E64
pdb bound state: IntermediateAnalogue
  pdb: 1au0A
  ligand het code: SDK
pdb bound state: IntermediateAnalogue
  pdb: 1au2A
  ligand het code: POS
pdb bound state: IntermediateAnalogue
  pdb: 1au3A
  ligand het code: PCM
pdb bound state: IntermediateAnalogue
  pdb: 1au4A
  ligand het code: INP
pdb bound state: IntermediateAnalogue
  pdb: 1ayuA
  ligand het code: INA
pdb bound state: IntermediateAnalogue
  pdb: 1ayvA
  ligand het code: IN6
pdb bound state: IntermediateAnalogue
  pdb: 1aywA
  ligand het code: IN3
pdb bound state: IntermediateAnalogue
  pdb: 1bgoA
  ligand het code: I10
pdb bound state: Unbound
  pdb: 1by8A
pdb bound state: IntermediateAnalogue
  pdb: 1memA
  ligand het code: BZP-LEU-NFP-BNS
references: Pycnodysostosis, a lysosomal disease caused by cathepsin K deficiency.
references: Proteolytic activity of human osteoclast cathepsin K. Expression, purification, activation, and substrate identification.
references: Structure and design of potent and selective cathepsin k inhibitors.
references: Crystal structure of human osteoclast cathepsin K complex with E-64.
references: Crystal structure of human cathepsin K complexed with a potent inhibitor.
references: Design of potent and selective human cathepsin K inhibitors that span the active site.
references: Autocatalytic activation of human cathepsin K.
references: Use of x-ray co-crystal structures and molecular modeling to design potent and selective non-peptide inhibitors of cathepsin k.
references: The crystal structure of human procathepsin K.
references: Crystal structure of wild-type human procathepsin K.
references: Inhibition of cathepsin K by nitric oxide donors: evidence for the formation of mixed disulfides and a sulfenic acid.
references: Preparation of active recombinant cathepsin K expressed in bacteria as inclusion body.
comment: This enzyme belongs to the peptidase family-C1. The literature [4] & [5] reported that the active-site triad of this enzyme comprises Cys25, His162, Asn182. Moreover, this cysteine residue play a catalytic role as nucleophile, which attack the substrate to form a covalent bond with it (see [4] & [5]).

Cathepsin B; Chain A
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/3.90.70.10
catalytic domain: index.html

Fibrinogen
type: KeggSubstrate
references: KEGG:C00393
compound type: peptide/protein

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

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

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

1atkA
type: Pdb
references: 1atk
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1atk
catalytic residue: GLN 19;CYS 25;HIS 162;ASN 182
main chain in catalysis: CYS 25

1au0A
type: Pdb
references: 1au0
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1au0
catalytic residue: GLN 19;CYS 25;HIS 162;ASN 182
main chain in catalysis: CYS 25

1au2A
type: Pdb
references: 1au2
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1au2
catalytic residue: GLN 19;CYS 25;HIS 162;ASN 182
main chain in catalysis: CYS 25

1au3A
type: Pdb
references: 1au3
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1au3
catalytic residue: GLN 19;CYS 25;HIS 162;ASN 182
main chain in catalysis: CYS 25

1au4A
type: Pdb
references: 1au4
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1au4
catalytic residue: GLN 19;CYS 25;HIS 162;ASN 182
main chain in catalysis: CYS 25

1ayuA
type: Pdb
references: 1ayu
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1ayu
catalytic residue: GLN 19;CYS 25;HIS 162;ASN 182
main chain in catalysis: CYS 25

1ayvA
type: Pdb
references: 1ayv
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1ayv
catalytic residue: GLN 19;CYS 25;HIS 162;ASN 182
main chain in catalysis: CYS 25

1aywA
type: Pdb
references: 1ayw
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1ayw
catalytic residue: GLN 19;CYS 25;HIS 162;ASN 182
main chain in catalysis: CYS 25

1bgoA
type: Pdb
references: 1bgo
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1bgo
catalytic residue: GLN 19;CYS 25;HIS 162;ASN 182
main chain in catalysis: CYS 25

1by8A
type: Pdb
references: 1by8
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1by8
catalytic residue: GLN 118;CYS 124;HIS 261;ASN 281
main chain in catalysis: CYS 124

1memA
type: Pdb
references: 1mem
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1mem
catalytic residue: GLN 19;CYS 25;HIS 159;ASN 175
main chain in catalysis: CYS 25

Pycnodysostosis, a lysosomal disease caused by cathepsin K deficiency.
type: BibliographicResource
comment: Variant Pycnodysostosis
medline id: 96355650
references: http://www.ncbi.nlm.nih.gov/pubmed/8703060
journal: Science
volume: 273
pages: 1236-8
published year: 1996
authors:
  item: Gelb BD
  item: Shi GP
  item: Chapman HA
  item: Desnick RJ
references: P43235

Proteolytic activity of human osteoclast cathepsin K. Expression, purification, activation, and substrate identification.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/8647860
journal: J Biol Chem
volume: 271
pages: 12517-24
published year: 1996
authors:
  item: Bossard MJ
  item: Tomaszek TA
  item: Thompson SK
  item: Amegadzie BY
  item: Hanning CR
  item: Jones C
  item: Kurdyla JT
  item: McNulty DE
  item: Drake FH
  item: Gowen M
  item: Levy MA

Structure and design of potent and selective cathepsin k inhibitors.
type: BibliographicResource
journal: J Am Chem Soc
volume: 119
pages: 11351-2
published year: 1997
authors:
  item: D.S.Yamashita
  item: W.W.Smith
  item: B.Zhao
  item: C.A.Janson
  item: T.A.Tomaszek
  item: M.J.Bossard
  item: M.A.Levy
  item: H.-J.Oh
  item: T.J.Carr
  item: S.K.Thompson
  item: C.F.Ijames
  item: S.A.Carr
  item: M.Mcqueney
  item: K.J.D'alessio
  item: B.Y.Amegadzie
  item: C.R.Hanning
  item: S.Abdel-Meguid
  item: R.L.Desjarlais
  item: J.G.Gleason
  item: D.F.Veber
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

Crystal structure of human osteoclast cathepsin K complex with E-64.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9033588
journal: Nat Struct Biol
volume: 4
pages: 109-11
published year: 1997
authors:
  item: Zhao B
  item: Janson CA
  item: Amegadzie BY
  item: D'Alessio K
  item: Griffin C
  item: Hanning CR
  item: Jones C
  item: Kurdyla J
  item: McQueney M
  item: Qiu X
  item: Smith WW
  item: Abdel-Meguid SS
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

Crystal structure of human cathepsin K complexed with a potent inhibitor.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9033587
journal: Nat Struct Biol
volume: 4
pages: 105-9
published year: 1997
authors:
  item: McGrath ME
  item: Klaus JL
  item: Barnes MG
  item: Bromme D
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

Design of potent and selective human cathepsin K inhibitors that span the active site.
type: BibliographicResource
comment: inhibitor designe (X-ray crystallography, MS, NMR, kinetic studies)
references: http://www.ncbi.nlm.nih.gov/pubmed/9405598
journal: Proc Natl Acad Sci U S A
volume: 94
pages: 14249-54
published year: 1997
authors:
  item: Thompson SK
  item: Halbert SM
  item: Bossard MJ
  item: Tomaszek TA
  item: Levy MA
  item: Zhao B
  item: Smith WW
  item: Abdel-Meguid SS
  item: Janson CA
  item: D'Alessio KJ
  item: McQueney MS
  item: Amegadzie BY
  item: Hanning CR
  item: DesJarlais RL
  item: Briand J
  item: Sarkar SK
  item: Huddleston MJ
  item: Ijames CF
  item: Carr SA
  item: Garnes KT
  item: Shu A
  item: Heys JR
  item: Bradbeer J
  item: Zembryki D
  item: Veber DF
  item: et al
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

Autocatalytic activation of human cathepsin K.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9153258
journal: J Biol Chem
volume: 272
pages: 13955-60
published year: 1997
authors:
  item: McQueney MS
  item: Amegadzie BY
  item: D'Alessio K
  item: Hanning CR
  item: McLaughlin MM
  item: McNulty D
  item: Carr SA
  item: Ijames C
  item: Kurdyla J
  item: Jones CS

Use of x-ray co-crystal structures and molecular modeling to design potent and selective non-peptide inhibitors of cathepsin k.
type: BibliographicResource
journal: J Am Chem Soc
volume: 120
pages: 9114-5
published year: 1998
authors:
  item: R.L.Desjarlais
  item: D.S.Yamashita
  item: H.J.Oh
  item: I.N.Uzinskas
  item: K.F.Erhard
  item: A.C.Allen
  item: R.C.Haltiwanger
  item: B.G.Zhao
  item: W.W.Smith
  item: S.S.Abdel-Meguid
  item: K.Dalessio
  item: C.A.Janson
  item: M.S.Mcqueney
  item: T.A.Tomaszek
  item: M.A.Levy
  item: D.F.Veber
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

The crystal structure of human procathepsin K.
type: BibliographicResource
comment: X-ray crystallography (2.8 Angstroms)
references: http://www.ncbi.nlm.nih.gov/pubmed/9893980
journal: Biochemistry
volume: 38
pages: 862-9
published year: 1999
authors:
  item: LaLonde JM
  item: Zhao B
  item: Janson CA
  item: D'Alessio KJ
  item: McQueney MS
  item: Orsini MJ
  item: Debouck CM
  item: Smith WW
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

Crystal structure of wild-type human procathepsin K.
type: BibliographicResource
comment: X-ray crystallography (3.2 Angstroms)
medline id: 99156066
references: http://www.ncbi.nlm.nih.gov/pubmed/10048321
journal: Protein Sci
volume: 8
pages: 283-90
published year: 1999
authors:
  item: Sivaraman J
  item: Lalumiere M
  item: Menard R
  item: Cygler M
references: P43235

Inhibition of cathepsin K by nitric oxide donors: evidence for the formation of mixed disulfides and a sulfenic acid.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10521264
journal: Biochemistry
volume: 38
pages: 13574-83
published year: 1999
authors:
  item: Percival MD
  item: Ouellet M
  item: Campagnolo C
  item: Claveau D
  item: Li C

Preparation of active recombinant cathepsin K expressed in bacteria as inclusion body.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/12182837
journal: Protein Expr Purif
volume: 25
pages: 541-6
published year: 2002
authors:
  item: Hwang HS
  item: Chung HS

ReferenceForCatalyticMechanism
reference index: 4
reference section: p.110

ReferenceForCatalyticMechanism
reference index: 5
reference section: p.106