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Hydrolase/hydrolase inhibitor
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PDB id
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1mem
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Contents |
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* Residue conservation analysis
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Enzyme class:
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E.C.3.4.22.38
- Cathepsin K.
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Reaction:
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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.
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Gene Ontology (GO) functional annotation
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Biological process
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proteolysis
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1 term
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Biochemical function
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cysteine-type peptidase activity
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2 terms
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DOI no:
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Nat Struct Biol
4:105-109
(1997)
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PubMed id:
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Crystal structure of human cathepsin K complexed with a potent inhibitor.
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M.E.McGrath,
J.L.Klaus,
M.G.Barnes,
D.Brömme.
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ABSTRACT
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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L.Mendieta,
A.Picó,
T.Tarragó,
M.Teixidó,
M.Castillo,
L.Rafecas,
A.Moyano,
and
E.Giralt
(2010).
Novel peptidyl aryl vinyl sulfones as highly potent and selective inhibitors of cathepsins L and B.
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| |
ChemMedChem, 5,
1556-1567.
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E.T.Larson,
F.Parussini,
M.H.Huynh,
J.D.Giebel,
A.M.Kelley,
L.Zhang,
M.Bogyo,
E.A.Merritt,
and
V.B.Carruthers
(2009).
Toxoplasma gondii cathepsin L is the primary target of the invasion-inhibitory compound morpholinurea-leucyl-homophenyl-vinyl sulfone phenyl.
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| |
J Biol Chem, 284,
26839-26850.
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PDB code:
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F.R.Salsbury,
S.T.Knutson,
L.B.Poole,
and
J.S.Fetrow
(2008).
Functional site profiling and electrostatic analysis of cysteines modifiable to cysteine sulfenic acid.
|
| |
Protein Sci, 17,
299-312.
|
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M.Mihelic,
A.Dobersek,
G.Guncar,
and
D.Turk
(2008).
Inhibitory fragment from the p41 form of invariant chain can regulate activity of cysteine cathepsins in antigen presentation.
|
| |
J Biol Chem, 283,
14453-14460.
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M.Ravikumar,
S.Pavan,
S.Bairy,
A.B.Pramod,
M.Sumakanth,
M.Kishore,
and
T.Sumithra
(2008).
Virtual screening of cathepsin k inhibitors using docking and pharmacophore models.
|
| |
Chem Biol Drug Des, 72,
79-90.
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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.
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J.Selent,
J.Kaleta,
Z.Li,
G.Lalmanach,
and
D.Brömme
(2007).
Selective inhibition of the collagenase activity of cathepsin K.
|
| |
J Biol Chem, 282,
16492-16501.
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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.
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W.C.Black,
and
M.D.Percival
(2006).
The consequences of lysosomotropism on the design of selective cathepsin K inhibitors.
|
| |
Chembiochem, 7,
1525-1535.
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A.Rossi,
Q.Deveraux,
B.Turk,
and
A.Sali
(2004).
Comprehensive search for cysteine cathepsins in the human genome.
|
| |
Biol Chem, 385,
363-372.
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M.Fabra,
and
J.Cerdà
(2004).
Ovarian cysteine proteinases in the teleost Fundulus heteroclitus: molecular cloning and gene expression during vitellogenesis and oocyte maturation.
|
| |
Mol Reprod Dev, 67,
282-294.
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O.B.De Oliveira Neto,
J.A.Batista,
D.J.Rigden,
O.L.Franco,
R.R.Fragoso,
A.C.Monteiro,
R.G.Monnerat,
and
M.F.Grossi-De-Sa
(2004).
Molecular cloning of a cysteine proteinase cDNA from the cotton boll weevil Anthonomus grandis (Coleoptera: Curculionidae).
|
| |
Biosci Biotechnol Biochem, 68,
1235-1242.
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A.Nayeem,
S.Krystek,
and
T.Stouch
(2003).
An assessment of protein-ligand binding site polarizability.
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| |
Biopolymers, 70,
201-211.
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M.E.McGrath,
P.A.Sprengeler,
C.M.Hill,
V.Martichonok,
H.Cheung,
J.R.Somoza,
J.T.Palmer,
and
J.W.Janc
(2003).
Peptide ketobenzoxazole inhibitors bound to cathepsin K.
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| |
Biochemistry, 42,
15018-15028.
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F.Lecaille,
Y.Choe,
W.Brandt,
Z.Li,
C.S.Craik,
and
D.Brömme
(2002).
Selective inhibition of the collagenolytic activity of human cathepsin K by altering its S2 subsite specificity.
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| |
Biochemistry, 41,
8447-8454.
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G.Lalmanach,
A.Boulangé,
C.Serveau,
F.Lecaille,
J.Scharfstein,
F.Gauthier,
and
E.Authié
(2002).
Congopain from Trypanosoma congolense: drug target and vaccine candidate.
|
| |
Biol Chem, 383,
739-749.
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Z.Li,
W.S.Hou,
C.R.Escalante-Torres,
B.D.Gelb,
and
D.Bromme
(2002).
Collagenase activity of cathepsin K depends on complex formation with chondroitin sulfate.
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| |
J Biol Chem, 277,
28669-28676.
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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.
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J.R.Somoza,
H.Zhan,
K.K.Bowman,
L.Yu,
K.D.Mortara,
J.T.Palmer,
J.M.Clark,
and
M.E.McGrath
(2000).
Crystal structure of human cathepsin V.
|
| |
Biochemistry, 39,
12543-12551.
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PDB code:
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L.S.Brinen,
E.Hansell,
J.Cheng,
W.R.Roush,
J.H.McKerrow,
and
R.J.Fletterick
(2000).
A target within the target: probing cruzain's P1' site to define structural determinants for the Chagas' disease protease.
|
| |
Structure, 8,
831-840.
|
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PDB codes:
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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.
|
|
|
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|
|
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.
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
C.Serveau,
G.Lalmanach,
I.Hirata,
J.Scharfstein,
M.A.Juliano,
and
F.Gauthier
(1999).
Discrimination of cruzipain, the major cysteine proteinase of Trypanosoma cruzi, and mammalian cathepsins B and L, by a pH-inducible fluorogenic substrate of trypanosomal cysteine proteinases.
|
| |
Eur J Biochem, 259,
275-280.
|
|
|
|
|
|
|
D.A.Jones,
and
F.A.Fitzpatrick
(1999).
Genomics and the discovery of new drug targets.
|
| |
Curr Opin Chem Biol, 3,
71-76.
|
|
|
|
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|
|
J.Herold,
S.G.Siddell,
and
A.E.Gorbalenya
(1999).
A human RNA viral cysteine proteinase that depends upon a unique Zn2+-binding finger connecting the two domains of a papain-like fold .
|
| |
J Biol Chem, 274,
14918-14925.
|
|
|
|
|
|
|
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:
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|
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|
|
M.E.McGrath
(1999).
The lysosomal cysteine proteases.
|
| |
Annu Rev Biophys Biomol Struct, 28,
181-204.
|
|
|
|
|
|
|
W.S.Hou,
D.Brömme,
Y.Zhao,
E.Mehler,
C.Dushey,
H.Weinstein,
C.S.Miranda,
C.Fraga,
F.Greig,
J.Carey,
D.L.Rimoin,
R.J.Desnick,
and
B.D.Gelb
(1999).
Characterization of novel cathepsin K mutations in the pro and mature polypeptide regions causing pycnodysostosis.
|
| |
J Clin Invest, 103,
731-738.
|
|
|
|
|
|
|
A.S.Ripka,
and
D.H.Rich
(1998).
Peptidomimetic design.
|
| |
Curr Opin Chem Biol, 2,
441-452.
|
|
|
|
|
|
|
B.Wang,
G.P.Shi,
P.M.Yao,
Z.Li,
H.A.Chapman,
and
D.Brömme
(1998).
Human cathepsin F. Molecular cloning, functional expression, tissue localization, and enzymatic characterization.
|
| |
J Biol Chem, 273,
32000-32008.
|
|
|
|
|
|
|
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.
|
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PDB code:
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|
|
M.E.McGrath,
J.T.Palmer,
D.Brömme,
and
J.R.Somoza
(1998).
Crystal structure of human cathepsin S.
|
| |
Protein Sci, 7,
1294-1302.
|
|
|
|
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|
|
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.
|
|
|
|
|
|
|
M.Gowen
(1997).
Inhibition of cathepsin K--a novel approach to antiresorptive therapy.
|
| |
Expert Opin Investig Drugs, 6,
1199-1202.
|
|
|
|
|
|
|
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.
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Links
