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Hydrolase PDB id
1by8
Jmol
Contents
Protein chain
310 a.a. *
* Residue conservation analysis
PDB id:
1by8
Name: Hydrolase
Title: The crystal structure of human procathepsin k
Structure: Protein (procathepsin k). Chain: a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
2.60Å     R-factor:   0.214     R-free:   0.344
Authors: J.M.Lalonde,B.Zhao,W.W.Smith,C.A.Janson,R.L.Desjarlais, T.A.Tomaszek,T.J.Carr,S.K.Thompson,D.S.Yamashita,D.F.Veber, S.S.Abdel-Mequid
Key ref:
J.M.LaLonde et al. (1999). The crystal structure of human procathepsin K. Biochemistry, 38, 862-869. PubMed id: 9893980 DOI: 10.1021/bi9822271
Date:
27-Oct-98     Release date:   24-Oct-99    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P43235  (CATK_HUMAN) -  Cathepsin K
Seq:
Struc: 		329 a.a.
310 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.3.4.22.38  - Cathepsin K.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: 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.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular space   3 terms 
  Biological process     bone resorption   3 terms 
  Biochemical function     protein binding     5 terms  

 

 
DOI no: 10.1021/bi9822271 Biochemistry 38:862-869 (1999)
PubMed id: 9893980  
 
 
The crystal structure of human procathepsin K.
J.M.LaLonde, B.Zhao, C.A.Janson, K.J.D'Alessio, M.S.McQueney, M.J.Orsini, C.M.Debouck, W.W.Smith.
 
  ABSTRACT  
 
Cathepsin K is a cysteine protease present in human osteoclasts that plays an important role in bone resorption. Cathepsin K is synthesized as an inactive proenzyme and activated under conditions of low pH. Autoproteolytic processing of the N-terminal 99 amino acid propeptide produces the active, mature form of cathepsin K. It is presumed that the activation of procathepsin K in vivo occurs in the bone resorption pit, which has a low-pH environment. We have determined the structure of human procathepsin K at 2.8 A resolution. The structure of the mature enzyme domain within procathepsin K is virtually identical to that of mature cathepsin K. The fold of the propeptide of procathepsin K is similar to that observed in procathepsins B and L despite differences in length and sequence. A portion of the propeptide occupies the active site cleft of cathepsin K. Hydrophobic interactions, salt bridges, and hydrogen-bonding interactions are observed in the structure of the propeptide and between the propeptide and the mature enzyme of procathepsin K. These interactions suggest an explanation for the stability of the proenzyme. The structure of procathepsin K contributes to an understanding of the molecular basis of inhibition by the propeptide portion of the molecule and activation of this important member of the cysteine protease family.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20921628 J.Reiser, B.Adair, and T.Reinheckel (2010).
Specialized roles for cysteine cathepsins in health and disease.
  J Clin Invest, 120, 3421-3431.  
20345903 M.Fairhead, and L.Thöny-Meyer (2010).
Role of the C-terminal extension in a bacterial tyrosinase.
  FEBS J, 277, 2083-2095.  
19910310 R.M.Deshapriya, S.Yuhashi, M.Usui, T.Kageyama, and Y.Yamamoto (2010).
Identification of essential residues of CTLA-2alpha for inhibitory potency.
  J Biochem, 147, 393-404.  
19479029 K.C.Pandey, D.T.Barkan, A.Sali, and P.J.Rosenthal (2009).
Regulatory elements within the prodomain of falcipain-2, a cysteine protease of the malaria parasite Plasmodium falciparum.
  PLoS One, 4, e5694.  
19040358 K.Schilling, A.Körner, S.Sehmisch, A.Kreusch, R.Kleint, Y.Benedix, A.Schlabrakowski, and B.Wiederanders (2009).
Selectivity of propeptide-enzyme interaction in cathepsin L-like cysteine proteases.
  Biol Chem, 390, 167-174.  
17206399 A.F.Schilling, C.Mülhausen, W.Lehmann, R.Santer, T.Schinke, J.M.Rueger, and M.Amling (2007).
High bone mineral density in pycnodysostotic patients with a novel mutation in the propeptide of cathepsin K.
  Osteoporos Int, 18, 659-669.  
17298440 F.C.Reis, T.F.Costa, T.Sulea, A.Mezzetti, J.Scharfstein, D.Brömme, R.Ménard, and A.P.Lima (2007).
The propeptide of cruzipain--a potent selective inhibitor of the trypanosomal enzymes cruzipain and brucipain, and of the human enzyme cathepsin F.
  FEBS J, 274, 1224-1234.  
17242381 M.Kliemannel, R.Golbik, R.Rudolph, E.Schwarz, and H.Lilie (2007).
The pro-peptide of proNGF: structure formation and intramolecular association with NGF.
  Protein Sci, 16, 411-419.  
17075137 G.Kaulmann, G.J.Palm, K.Schilling, R.Hilgenfeld, and B.Wiederanders (2006).
The crystal structure of a Cys25 -> Ala mutant of human procathepsin S elucidates enzyme-prosequence interactions.
  Protein Sci, 15, 2619-2629.
PDB code: 2c0y
16650055 E.Wieczerzak, E.Jankowska, S.Rodziewicz-Motowidło, A.Giełdoń, J.Lagiewka, Z.Grzonka, M.Abrahamson, A.Grubb, and D.Brömme (2005).
Novel azapeptide inhibitors of cathepsins B and K. Structural background to increased specificity for cathepsin B.
  J Pept Res, 66, 1.  
15195995 A.Rossi, Q.Deveraux, B.Turk, and A.Sali (2004).
Comprehensive search for cysteine cathepsins in the human genome.
  Biol Chem, 385, 363-372.  
14625277 K.C.Pandey, P.S.Sijwali, A.Singh, B.K.Na, and P.J.Rosenthal (2004).
Independent intramolecular mediators of folding, activity, and inhibition for the Plasmodium falciparum cysteine protease falcipain-2.
  J Biol Chem, 279, 3484-3491.  
12860980 D.N.Li, S.P.Matthews, A.N.Antoniou, D.Mazzeo, and C.Watts (2003).
Multistep autoactivation of asparaginyl endopeptidase in vitro and in vivo.
  J Biol Chem, 278, 38980-38990.  
12554931 D.Turk, and G.Guncar (2003).
Lysosomal cysteine proteases (cathepsins): promising drug targets.
  Acta Crystallogr D Biol Crystallogr, 59, 203-213.  
12437139 S.Pietschmann, M.Fehn, G.Kaulmann, I.Wenz, B.Wiederanders, and K.Schilling (2002).
Foldase function of the cathepsin S proregion is strictly based upon its domain structure.
  Biol Chem, 383, 1453-1458.  
11517942 K.Schilling, S.Pietschmann, M.Fehn, I.Wenz, and B.Wiederanders (2001).
Folding incompetence of cathepsin L-like cysteine proteases may be compensated by the highly conserved, domain-building N-terminal extension of the proregion.
  Biol Chem, 382, 859-865.  
10760593 K.Sol-Church, J.Frenck, and R.W.Mason (2000).
Mouse cathepsin M, a placenta-specific lysosomal cysteine protease related to cathepsins L and P.
  Biochim Biophys Acta, 1491, 289-294.  
10679409 R.J.Riese, and H.A.Chapman (2000).
Cathepsins and compartmentalization in antigen presentation.
  Curr Opin Immunol, 12, 107-113.  
10806395 S.Kreusch, M.Fehn, G.Maubach, K.Nissler, W.Rommerskirch, K.Schilling, E.Weber, I.Wenz, and B.Wiederanders (2000).
An evolutionarily conserved tripartite tryptophan motif stabilizes the prodomains of cathepsin L-like cysteine proteases.
  Eur J Biochem, 267, 2965-2972.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.