DB code: S00451

RLCP classification 1.13.30000.44 : Hydrolysis
CATH domain 3.90.70.10 : Cathepsin B; Chain A Catalytic domain
E.C. 3.4.22.38
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
3.90.70.10 : Cathepsin B; Chain A S00444 S00445 S00447 S00448 S00449 S00450 S00446 S00518

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq MEROPS Pfam
P43235 Cathepsin K
EC 3.4.22.38
Cathepsin O
Cathepsin X
Cathepsin O2
NP_000387.1 (Protein)
NM_000396.3 (DNA/RNA sequence)
I29.007 ()
PF08246 (Inhibitor_I29)
PF00112 (Peptidase_C1)
[Graphical View]

KEGG enzyme name
cathepsin K
cathepsin O and cathepsin X (both misleading, having been used forother enzymes)
cathepsin O2

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P43235 CATK_HUMAN Broad proteolytic activity. With small- molecule substrates and inhibitors, the major determinant of specificity is P2, which is preferably Leu, Met > Phe, and not Arg. Lysosome.

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C00393 C00001 C00017 C00012
E.C.
Compound Fibrinogen H2O Protein Peptide
Type peptide/protein H2O peptide/protein peptide/protein
ChEBI 15377
 15377
PubChem 22247451
 962
 22247451
 962
1atkA Unbound Unbound Unbound Intermediate-analogue:E64
1au0A Unbound Unbound Unbound Intermediate-analogue:SDK
1au2A Unbound Unbound Unbound Intermediate-analogue:POS
1au3A Unbound Unbound Unbound Intermediate-analogue:PCM
1au4A Unbound Unbound Unbound Intermediate-analogue:INP
1ayuA Unbound Unbound Unbound Intermediate-analogue:INA
1ayvA Unbound Unbound Unbound Intermediate-analogue:IN6
1aywA Unbound Unbound Unbound Intermediate-analogue:IN3
1bgoA Unbound Unbound Unbound Intermediate-analogue:I10
1by8A Unbound Unbound Unbound Unbound
1memA Unbound Unbound Unbound Intermediate-analogue:BZP-LEU-NFP-BNS

Reference for Active-site residues
resource references E.C.

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1atkA GLN 19;CYS 25;HIS 162;ASN 182 CYS 25
1au0A GLN 19;CYS 25;HIS 162;ASN 182 CYS 25
1au2A GLN 19;CYS 25;HIS 162;ASN 182 CYS 25
1au3A GLN 19;CYS 25;HIS 162;ASN 182 CYS 25
1au4A GLN 19;CYS 25;HIS 162;ASN 182 CYS 25
1ayuA GLN 19;CYS 25;HIS 162;ASN 182 CYS 25
1ayvA GLN 19;CYS 25;HIS 162;ASN 182 CYS 25
1aywA GLN 19;CYS 25;HIS 162;ASN 182 CYS 25
1bgoA GLN 19;CYS 25;HIS 162;ASN 182 CYS 25
1by8A GLN 118;CYS 124;HIS 261;ASN 281 CYS 124
1memA GLN 19;CYS 25;HIS 159;ASN 175 CYS 25

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[4]
p.110
[5]
p.106

References
[1]
Resource
Comments Variant Pycnodysostosis
Medline ID 96355650
PubMed ID 8703060
Journal Science
Year 1996
Volume 273
Pages 1236-8
Authors Gelb BD, Shi GP, Chapman HA, Desnick RJ
Title Pycnodysostosis, a lysosomal disease caused by cathepsin K deficiency.
Related PDB
Related UniProtKB P43235
[2]
Resource
Comments
Medline ID
PubMed ID 8647860
Journal J Biol Chem
Year 1996
Volume 271
Pages 12517-24
Authors Bossard MJ, Tomaszek TA, Thompson SK, Amegadzie BY, Hanning CR, Jones C, Kurdyla JT, McNulty DE, Drake FH, Gowen M, Levy MA
Title Proteolytic activity of human osteoclast cathepsin K. Expression, purification, activation, and substrate identification.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID
Journal J Am Chem Soc
Year 1997
Volume 119
Pages 11351-2
Authors D.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
Title Structure and design of potent and selective cathepsin k inhibitors.
Related PDB 1au0 1au2 1au3 1au4
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 9033588
Journal Nat Struct Biol
Year 1997
Volume 4
Pages 109-11
Authors Zhao 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
Title Crystal structure of human osteoclast cathepsin K complex with E-64.
Related PDB 1atk
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 9033587
Journal Nat Struct Biol
Year 1997
Volume 4
Pages 105-9
Authors McGrath ME, Klaus JL, Barnes MG, Bromme D
Title Crystal structure of human cathepsin K complexed with a potent inhibitor.
Related PDB 1mem
Related UniProtKB
[6]
Resource
Comments inhibitor designe (X-ray crystallography, MS, NMR, kinetic studies)
Medline ID
PubMed ID 9405598
Journal Proc Natl Acad Sci U S A
Year 1997
Volume 94
Pages 14249-54
Authors Thompson 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
Title Design of potent and selective human cathepsin K inhibitors that span the active site.
Related PDB 1ayu 1ayv 1ayw
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 9153258
Journal J Biol Chem
Year 1997
Volume 272
Pages 13955-60
Authors McQueney MS, Amegadzie BY, D'Alessio K, Hanning CR, McLaughlin MM, McNulty D, Carr SA, Ijames C, Kurdyla J, Jones CS
Title Autocatalytic activation of human cathepsin K.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID
Journal J Am Chem Soc
Year 1998
Volume 120
Pages 9114-5
Authors R.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
Title Use of x-ray co-crystal structures and molecular modeling to design potent and selective non-peptide inhibitors of cathepsin k.
Related PDB 1bgo
Related UniProtKB
[9]
Resource
Comments X-ray crystallography (2.8 Angstroms)
Medline ID
PubMed ID 9893980
Journal Biochemistry
Year 1999
Volume 38
Pages 862-9
Authors LaLonde JM, Zhao B, Janson CA, D'Alessio KJ, McQueney MS, Orsini MJ, Debouck CM, Smith WW
Title The crystal structure of human procathepsin K.
Related PDB 1by8
Related UniProtKB
[10]
Resource
Comments X-ray crystallography (3.2 Angstroms)
Medline ID 99156066
PubMed ID 10048321
Journal Protein Sci
Year 1999
Volume 8
Pages 283-90
Authors Sivaraman J, Lalumiere M, Menard R, Cygler M
Title Crystal structure of wild-type human procathepsin K.
Related PDB
Related UniProtKB P43235
[11]
Resource
Comments
Medline ID
PubMed ID 10521264
Journal Biochemistry
Year 1999
Volume 38
Pages 13574-83
Authors Percival MD, Ouellet M, Campagnolo C, Claveau D, Li C
Title Inhibition of cathepsin K by nitric oxide donors: evidence for the formation of mixed disulfides and a sulfenic acid.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 12182837
Journal Protein Expr Purif
Year 2002
Volume 25
Pages 541-6
Authors Hwang HS, Chung HS
Title Preparation of active recombinant cathepsin K expressed in bacteria as inclusion body.
Related PDB
Related UniProtKB

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]).

Created Updated
2002-07-01 2010-02-02