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Hydrolase PDB id
1atk
Jmol
Contents
Protein chain
215 a.a. *
Ligands
E64
Waters ×28
* Residue conservation analysis
PDB id:
1atk
Name: Hydrolase
Title: Crystal structure of the cysteine protease human cathepsin k in complex with the covalent inhibitor e-64
Structure: Cathepsin k. Chain: a. Engineered: yes. Other_details: inhibitor e-64 covalent link between inhibitor atom c2 and the sulfur of cys 25
Source: Homo sapiens. Human. Organism_taxid: 9606. Cell_line: sf21. Cell: human osteoclasts. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf21.
Resolution:
2.20Å     R-factor:   0.215     R-free:   0.310
Authors: B.Zhao,W.W.Smith,C.A.Janson,S.S.Abdel-Meguid
Key ref: B.Zhao et al. (1997). Crystal structure of human osteoclast cathepsin K complex with E-64. Nat Struct Biol, 4, 109-111. PubMed id: 9033588 DOI: 10.1038/nsb0297-109
Date:
19-Dec-96     Release date:   04-Feb-98    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P43235  (CATK_HUMAN) -  Cathepsin K
Seq:
Struc: 		329 a.a.
215 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!
  Biological process     proteolysis   1 term 
  Biochemical function     cysteine-type peptidase activity     2 terms  

 

 
DOI no: 10.1038/nsb0297-109 Nat Struct Biol 4:109-111 (1997)
PubMed id: 9033588  
 
 
Crystal structure of human osteoclast cathepsin K complex with E-64.
B.Zhao, C.A.Janson, B.Y.Amegadzie, K.D'Alessio, C.Griffin, C.R.Hanning, C.Jones, J.Kurdyla, M.McQueney, X.Qiu, W.W.Smith, S.S.Abdel-Meguid.
 
  ABSTRACT  
 
No abstract given.

 

Literature references that cite this PDB file's key reference

  PubMed id Reference
18664521 S.Tada, K.Tsutsumi, H.Ishihara, K.Suzuki, K.Gohda, and N.Teno (2008).
Species differences between human and rat in the substrate specificity of cathepsin K.
  J Biochem, 144, 499-506.  
18516623 W.E.Müller, X.Wang, K.Kropf, A.Boreiko, U.Schlossmacher, D.Brandt, H.C.Schröder, and M.Wiens (2008).
Silicatein expression in the hexactinellid Crateromorpha meyeri: the lead marker gene restricted to siliceous sponges.
  Cell Tissue Res, 333, 339-351.  
17452780 J.A.Gavira, L.A.González-Ramírez, M.C.Oliver-Salvador, M.Soriano-García, and J.M.García-Ruiz (2007).
Structure of the mexicain-E-64 complex and comparison with other cysteine proteases of the papain family.
  Acta Crystallogr D Biol Crystallogr, 63, 555-563.  
17935329 S.Ma, L.S.Devi-Kesavan, and J.Gao (2007).
Molecular dynamics simulations of the catalytic pathway of a cysteine protease: a combined QM/MM study of human cathepsin K.
  J Am Chem Soc, 129, 13633-13645.  
16358325 T.Sulea, H.A.Lindner, E.O.Purisima, and R.Ménard (2006).
Binding site-based classification of coronaviral papain-like proteases.
  Proteins, 62, 760-775.  
16149114 C.Drahl, B.F.Cravatt, and E.J.Sorensen (2005).
Protein-reactive natural products.
  Angew Chem Int Ed Engl, 44, 5788-5809.  
15843150 P.Meh, M.Pavsic, V.Turk, A.Baici, and B.Lenarcic (2005).
Dual concentration-dependent activity of thyroglobulin type-1 domain of testican: specific inhibitor and substrate of cathepsin L.
  Biol Chem, 386, 75-83.  
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.  
12833545 M.Sulpizi, A.Laio, J.VandeVondele, A.Cattaneo, U.Rothlisberger, and P.Carloni (2003).
Reaction mechanism of caspases: insights from QM/MM Car-Parrinello simulations.
  Proteins, 52, 212-224.  
12668429 M.Sulpizi, U.Rothlisberger, and P.Carloni (2003).
Molecular dynamics studies of caspase-3.
  Biophys J, 84, 2207-2215.  
12592020 Y.A.Sabnis, P.V.Desai, P.J.Rosenthal, and M.A.Avery (2003).
Probing the structure of falcipain-3, a cysteine protease from Plasmodium falciparum: comparative protein modeling and docking studies.
  Protein Sci, 12, 501-509.  
  12401493 D.C.Greenbaum, W.D.Arnold, F.Lu, L.Hayrapetian, A.Baruch, J.Krumrine, S.Toba, K.Chehade, D.Brömme, I.D.Kuntz, and M.Bogyo (2002).
Small molecule affinity fingerprinting. A tool for enzyme family subclassification, target identification, and inhibitor design.
  Chem Biol, 9, 1085-1094.  
11322895 F.Lecaille, E.Authié, T.Moreau, C.Serveau, F.Gauthier, and G.Lalmanach (2001).
Subsite specificity of trypanosomal cathepsin L-like cysteine proteases. Probing the S2 pocket with phenylalanine-derived amino acids.
  Eur J Biochem, 268, 2733-2741.  
10836133 C.Debouck, and B.Metcalf (2000).
The impact of genomics on drug discovery.
  Annu Rev Pharmacol Toxicol, 40, 193-207.  
10971478 R.Furmonaviciene, H.F.Sewell, and F.Shakib (2000).
Comparative molecular modelling identifies a common putative IgE epitope on cysteine protease allergens of diverse sources.
  Clin Exp Allergy, 30, 1307-1313.  
  10716634 R.I.Brinkworth, J.F.Tort, P.J.Brindley, and J.P.Dalton (2000).
Phylogenetic relationships and theoretical model of human cathepsin W (lymphopain), a cysteine proteinase from cytotoxic T lymphocytes.
  Int J Biochem Cell Biol, 32, 373-384.  
  11152132 S.Estrada, S.T.Olson, E.Raub-Segall, and I.Björk (2000).
The N-terminal region of cystatin A (stefin A) binds to papain subsequent to the two hairpin loops of the inhibitor. Demonstration of two-step binding by rapid-kinetic studies of cystatin A labeled at the N-terminus with a fluorescent reporter group.
  Protein Sci, 9, 2218-2224.  
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.  
10350606 C.Czaplewski, Z.Grzonka, M.Jaskólski, F.Kasprzykowski, M.Kozak, E.Politowska, and J.Ciarkowski (1999).
Binding modes of a new epoxysuccinyl-peptide inhibitor of cysteine proteases. Where and how do cysteine proteases express their selectivity?
  Biochim Biophys Acta, 1431, 290-305.  
  10021407 D.A.Jones, and F.A.Fitzpatrick (1999).
Genomics and the discovery of new drug targets.
  Curr Opin Chem Biol, 3, 71-76.  
9893980 J.M.LaLonde, B.Zhao, C.A.Janson, K.J.D'Alessio, M.S.McQueney, M.J.Orsini, C.M.Debouck, and W.W.Smith (1999).
The crystal structure of human procathepsin K.
  Biochemistry, 38, 862-869.
PDB code: 1by8
  10048321 J.Sivaraman, M.Lalumière, R.Ménard, and M.Cygler (1999).
Crystal structure of wild-type human procathepsin K.
  Protein Sci, 8, 283-290.
PDB code: 7pck
  10077535 L.D.Greller, and F.L.Tobin (1999).
Detecting selective expression of genes and proteins.
  Genome Res, 9, 282-296.  
10410800 M.E.McGrath (1999).
The lysosomal cysteine proteases.
  Annu Rev Biophys Biomol Struct, 28, 181-204.  
10470376 N.Katunuma, A.Matsui, T.Kakegawa, E.Murata, T.Asao, and Y.Ohba (1999).
Study of the functional share of lysosomal cathepsins by the development of specific inhibitors.
  Adv Enzyme Regul, 39, 247-260.  
10698261 R.Ishisaka, T.Utsumi, T.Kanno, K.Arita, N.Katunuma, J.Akiyama, and K.Utsumi (1999).
Participation of a cathepsin L-type protease in the activation of caspase-3.
  Cell Struct Funct, 24, 465-470.  
  9524065 D.Turk, G.Guncar, M.Podobnik, and B.Turk (1998).
Revised definition of substrate binding sites of papain-like cysteine proteases.
  Biol Chem, 379, 137-147.  
  9493267 G.Guncar, M.Podobnik, J.Pungercar, B.Strukelj, V.Turk, and D.Turk (1998).
Crystal structure of porcine cathepsin H determined at 2.1 A resolution: location of the mini-chain C-terminal carboxyl group defines cathepsin H aminopeptidase function.
  Structure, 6, 51-61.
PDB code: 8pch
  9655332 M.E.McGrath, J.T.Palmer, D.Brömme, and J.R.Somoza (1998).
Crystal structure of human cathepsin S.
  Protein Sci, 7, 1294-1302.  
9843405 N.Campobasso, C.A.Costello, C.Kinsland, T.P.Begley, and S.E.Ealick (1998).
Crystal structure of thiaminase-I from Bacillus thiaminolyticus at 2.0 A resolution.
  Biochemistry, 37, 15981-15989.
PDB codes: 2thi 3thi 4thi
9286755 B.J.Votta, M.A.Levy, A.Badger, J.Bradbeer, R.A.Dodds, I.E.James, S.Thompson, M.J.Bossard, T.Carr, J.R.Connor, T.A.Tomaszek, L.Szewczuk, F.H.Drake, D.F.Veber, and M.Gowen (1997).
Peptide aldehyde inhibitors of cathepsin K inhibit bone resorption both in vitro and in vivo.
  J Bone Miner Res, 12, 1396-1406.  
  9667859 D.F.Veber, F.H.Drake, and M.Gowen (1997).
The new partnership of genomics and chemistry for accelerated drug development.
  Curr Opin Chem Biol, 1, 151-156.  
15991895 M.Gowen (1997).
Inhibition of cathepsin K--a novel approach to antiresorptive therapy.
  Expert Opin Investig Drugs, 6, 1199-1202.  
9405598 S.K.Thompson, S.M.Halbert, M.J.Bossard, T.A.Tomaszek, M.A.Levy, B.Zhao, W.W.Smith, S.S.Abdel-Meguid, C.A.Janson, K.J.D'Alessio, M.S.McQueney, B.Y.Amegadzie, C.R.Hanning, R.L.DesJarlais, J.Briand, S.K.Sarkar, M.J.Huddleston, C.F.Ijames, S.A.Carr, K.T.Garnes, A.Shu, J.R.Heys, J.Bradbeer, D.Zembryki, L.Lee-Rykaczewski, I.E.James, M.W.Lark, F.H.Drake, M.Gowen, J.G.Gleason, and D.F.Veber (1997).
Design of potent and selective human cathepsin K inhibitors that span the active site.
  Proc Natl Acad Sci U S A, 94, 14249-14254.
PDB codes: 1ayu 1ayv 1ayw
  9468787 S.Rastan, and L.J.Beeley (1997).
Functional genomics: going forwards from the databases.
  Curr Opin Genet Dev, 7, 777-783.  
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.