EzCatDB: S00451
Related links:    PDB-formatted query search system Fasta-formatted query search system Fasta-formatted query search system

DB codeS00451
RLCP classification1.13.30000.44 : Hydrolysis
CATH domainDomain 13.90.70.10 : Cathepsin B; Chain ACatalytic domain
E.C.3.4.22.38

CATH domainRelated DB codes (homologues)
3.90.70.10 : Cathepsin B; Chain AS00444,S00445,S00447,S00448,S00449,S00450,S00446,S00518

Enzyme Name
UniProtKBKEGG

P43235
Protein nameCathepsin Kcathepsin K
cathepsin O and cathepsin X (both misleading, having been used forother enzymes)
cathepsin O2
SynonymsEC 3.4.22.38
Cathepsin O
Cathepsin X
Cathepsin O2
RefSeqNP_000387.1 (Protein)
NM_000396.3 (DNA/RNA sequence)
PfamPF08246 (Inhibitor_I29)
PF00112 (Peptidase_C1)
[Graphical view]


UniProtKB:Accession NumberP43235
Entry nameCATK_HUMAN
ActivityBroad proteolytic activity. With small- molecule substrates and inhibitors, the major determinant of specificity is P2, which is preferably Leu, Met > Phe, and not Arg.
Subunit
Subcellular locationLysosome.
Cofactor

Compound table: links to PDB-related databases & PoSSuM

SubstratesProductsintermediates
KEGG-idC00393C00001C00017C00012
CompoundFibrinogenH2OProteinPeptide
Typepeptide/proteinH2Opeptide/proteinpeptide/protein
ChEBI
15377



PubChem
962
22247451



             
1atkAUnbound UnboundUnboundIntermediate-analogue:E64
1au0AUnbound UnboundUnboundIntermediate-analogue:SDK
1au2AUnbound UnboundUnboundIntermediate-analogue:POS
1au3AUnbound UnboundUnboundIntermediate-analogue:PCM
1au4AUnbound UnboundUnboundIntermediate-analogue:INP
1ayuAUnbound UnboundUnboundIntermediate-analogue:INA
1ayvAUnbound UnboundUnboundIntermediate-analogue:IN6
1aywAUnbound UnboundUnboundIntermediate-analogue:IN3
1bgoAUnbound UnboundUnboundIntermediate-analogue:I10
1by8AUnbound UnboundUnboundUnbound
1memAUnbound UnboundUnboundIntermediate-analogue:BZP-LEU-NFP-BNS

Active-site residues
pdbCatalytic residuesMain-chain involved in catalysis
          
1atkAGLN  19;CYS  25;HIS 162;ASN 182
CYS  25
1au0AGLN  19;CYS  25;HIS 162;ASN 182
CYS  25
1au2AGLN  19;CYS  25;HIS 162;ASN 182
CYS  25
1au3AGLN  19;CYS  25;HIS 162;ASN 182
CYS  25
1au4AGLN  19;CYS  25;HIS 162;ASN 182
CYS  25
1ayuAGLN  19;CYS  25;HIS 162;ASN 182
CYS  25
1ayvAGLN  19;CYS  25;HIS 162;ASN 182
CYS  25
1aywAGLN  19;CYS  25;HIS 162;ASN 182
CYS  25
1bgoAGLN  19;CYS  25;HIS 162;ASN 182
CYS  25
1by8AGLN 118;CYS 124;HIS 261;ASN 281
CYS 124
1memAGLN  19;CYS  25;HIS 159;ASN 175
CYS  25

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[4]p.110
[5]p.106

references
[1]
CommentsVariant Pycnodysostosis
Medline ID96355650
PubMed ID8703060
JournalScience
Year1996
Volume273
Pages1236-8
AuthorsGelb BD, Shi GP, Chapman HA, Desnick RJ
TitlePycnodysostosis, a lysosomal disease caused by cathepsin K deficiency.
Related UniProtKBP43235
[2]
PubMed ID8647860
JournalJ Biol Chem
Year1996
Volume271
Pages12517-24
AuthorsBossard MJ, Tomaszek TA, Thompson SK, Amegadzie BY, Hanning CR, Jones C, Kurdyla JT, McNulty DE, Drake FH, Gowen M, Levy MA
TitleProteolytic activity of human osteoclast cathepsin K. Expression, purification, activation, and substrate identification.
[3]
JournalJ Am Chem Soc
Year1997
Volume119
Pages11351-2
AuthorsD.S.Yamashita,W.W.Smith,B.Zhao,C.A.Janson,T.A.Tomaszek,M.J.Bossard,M.A.Levy,H.-J.Oh,T.J.Carr,S.K.Thompson,C.F.Ijames,S.A.Carr,M.Mcqueney,K.J.D'alessio,B.Y.Amegadzie,C.R.Hanning,S.Abdel-Meguid,R.L.Desjarlais,J.G.Gleason,D.F.Veber
TitleStructure and design of potent and selective cathepsin k inhibitors.
Related PDB1au0,1au2,1au3,1au4
[4]
PubMed ID9033588
JournalNat Struct Biol
Year1997
Volume4
Pages109-11
AuthorsZhao B, Janson CA, Amegadzie BY, D'Alessio K, Griffin C, Hanning CR, Jones C, Kurdyla J, McQueney M, Qiu X, Smith WW, Abdel-Meguid SS
TitleCrystal structure of human osteoclast cathepsin K complex with E-64.
Related PDB1atk
[5]
PubMed ID9033587
JournalNat Struct Biol
Year1997
Volume4
Pages105-9
AuthorsMcGrath ME, Klaus JL, Barnes MG, Bromme D
TitleCrystal structure of human cathepsin K complexed with a potent inhibitor.
Related PDB1mem
[6]
Commentsinhibitor designe (X-ray crystallography, MS, NMR, kinetic studies)
PubMed ID9405598
JournalProc Natl Acad Sci U S A
Year1997
Volume94
Pages14249-54
AuthorsThompson SK, Halbert SM, Bossard MJ, Tomaszek TA, Levy MA, Zhao B, Smith WW, Abdel-Meguid SS, Janson CA, D'Alessio KJ, McQueney MS, Amegadzie BY, Hanning CR, DesJarlais RL, Briand J, Sarkar SK, Huddleston MJ, Ijames CF, Carr SA, Garnes KT, Shu A, Heys JR, Bradbeer J, Zembryki D, Veber DF, et al
TitleDesign of potent and selective human cathepsin K inhibitors that span the active site.
Related PDB1ayu,1ayv,1ayw
[7]
PubMed ID9153258
JournalJ Biol Chem
Year1997
Volume272
Pages13955-60
AuthorsMcQueney MS, Amegadzie BY, D'Alessio K, Hanning CR, McLaughlin MM, McNulty D, Carr SA, Ijames C, Kurdyla J, Jones CS
TitleAutocatalytic activation of human cathepsin K.
[8]
JournalJ Am Chem Soc
Year1998
Volume120
Pages9114-5
AuthorsR.L.Desjarlais, D.S.Yamashita, H.J.Oh, I.N.Uzinskas, K.F.Erhard, A.C.Allen, R.C.Haltiwanger, B.G.Zhao, W.W.Smith, S.S.Abdel-Meguid, K.Dalessio, C.A.Janson, M.S.Mcqueney, T.A.Tomaszek, M.A.Levy, D.F.Veber
TitleUse of x-ray co-crystal structures and molecular modeling to design potent and selective non-peptide inhibitors of cathepsin k.
Related PDB1bgo
[9]
CommentsX-ray crystallography (2.8 Angstroms)
PubMed ID9893980
JournalBiochemistry
Year1999
Volume38
Pages862-9
AuthorsLaLonde JM, Zhao B, Janson CA, D'Alessio KJ, McQueney MS, Orsini MJ, Debouck CM, Smith WW
TitleThe crystal structure of human procathepsin K.
Related PDB1by8
[10]
CommentsX-ray crystallography (3.2 Angstroms)
Medline ID99156066
PubMed ID10048321
JournalProtein Sci
Year1999
Volume8
Pages283-90
AuthorsSivaraman J, Lalumiere M, Menard R, Cygler M
TitleCrystal structure of wild-type human procathepsin K.
Related UniProtKBP43235
[11]
PubMed ID10521264
JournalBiochemistry
Year1999
Volume38
Pages13574-83
AuthorsPercival MD, Ouellet M, Campagnolo C, Claveau D, Li C
TitleInhibition of cathepsin K by nitric oxide donors: evidence for the formation of mixed disulfides and a sulfenic acid.
[12]
PubMed ID12182837
JournalProtein Expr Purif
Year2002
Volume25
Pages541-6
AuthorsHwang HS, Chung HS
TitlePreparation of active recombinant cathepsin K expressed in bacteria as inclusion body.

comments
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]).

createdupdated
2002-07-012010-02-02


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
© Biotechnology Research Institute for Drug Discovery, AIST, 2015-2016 All Rights Reserved.
© Computational Biology Research Center, AIST, 2004-2016 All Rights Reserved.