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PDBsum entry 1cte
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Thiol protease
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PDB id
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1cte
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Contents |
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* Residue conservation analysis
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Enzyme class:
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E.C.3.4.22.1
- cathepsin B.
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Reaction:
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Hydrolysis of proteins with broad specificity for peptide bonds. Preferentially cleaves -Arg-Arg-|-Xaa bonds in small molecule substrates (thus differing from cathepsin L). In addition to being an endopeptidase, shows peptidyl-dipeptidase activity, liberating C-terminal dipeptides.
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J Biol Chem
270:5527-5533
(1995)
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PubMed id:
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Crystal structures of recombinant rat cathepsin B and a cathepsin B-inhibitor complex. Implications for structure-based inhibitor design.
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Z.Jia,
S.Hasnain,
T.Hirama,
X.Lee,
J.S.Mort,
R.To,
C.P.Huber.
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ABSTRACT
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The lysosomal cysteine proteinase cathepsin B (EC 3.4.22.1) plays an important
role in protein catabolism and has also been implicated in various disease
states. The crystal structures of two forms of native recombinant rat cathepsin
B have been determined. The overall folding of rat cathepsin B was shown to be
very similar to that of the human liver enzyme. The structure of the native
enzyme containing an underivatized active site cysteine (Cys29) showed the
active enzyme conformation to be similar to that determined previously for the
oxidized form. In a second structure Cys29 was derivatized with the reversible
blocking reagent pyridyl disulfide. In this structure large side chain
conformational changes were observed for the two key catalytic residues Cys29
and His199, demonstrating the potential flexibility of these side chains. In
addition the structure of the complex between rat cathepsin B and the inhibitor
benzyloxycarbonyl-Arg-Ser(O-Bzl) chloromethylketone was determined. The complex
structure showed that very little conformational change occurs in the enzyme
upon inhibitor binding. It also allowed visualization of the interaction between
the enzyme and inhibitor. In particular the interaction between Glu245 and the
P2 Arg residue was clearly demonstrated, and it was found that the benzyl group
of the P1 substrate residue occupies a large hydrophobic pocket thought to
represent the S'1 subsite. This may have important implications for
structure-based design of cathepsin B inhibitors.
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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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Q.Yao,
J.Cui,
Y.Zhu,
G.Wang,
L.Hu,
C.Long,
R.Cao,
X.Liu,
N.Huang,
S.Chen,
L.Liu,
and
F.Shao
(2009).
A bacterial type III effector family uses the papain-like hydrolytic activity to arrest the host cell cycle.
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Proc Natl Acad Sci U S A,
106,
3716-3721.
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PDB codes:
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E.Wieczerzak,
S.Rodziewicz-Motowidło,
E.Jankowska,
A.Giełdoń,
and
J.Ciarkowski
(2007).
An enormously active and selective azapeptide inhibitor of cathepsin B.
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J Pept Sci,
13,
536-543.
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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.
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J Pept Res,
66,
1.
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H.Li,
A.D.Robertson,
and
J.H.Jensen
(2005).
Very fast empirical prediction and rationalization of protein pKa values.
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Proteins,
61,
704-721.
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M.Zhu,
F.Shao,
R.W.Innes,
J.E.Dixon,
and
Z.Xu
(2004).
The crystal structure of Pseudomonas avirulence protein AvrPphB: a papain-like fold with a distinct substrate-binding site.
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Proc Natl Acad Sci U S A,
101,
302-307.
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PDB code:
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W.A.Judice,
L.Puzer,
S.S.Cotrin,
A.K.Carmona,
G.H.Coombs,
L.Juliano,
and
M.A.Juliano
(2004).
Carboxydipeptidase activities of recombinant cysteine peptidases. Cruzain of Trypanosoma cruzi and CPB of Leishmania mexicana.
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Eur J Biochem,
271,
1046-1053.
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D.Turk,
and
G.Guncar
(2003).
Lysosomal cysteine proteases (cathepsins): promising drug targets.
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Acta Crystallogr D Biol Crystallogr,
59,
203-213.
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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.
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Proteins,
52,
212-224.
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M.Sulpizi,
U.Rothlisberger,
and
P.Carloni
(2003).
Molecular dynamics studies of caspase-3.
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Biophys J,
84,
2207-2215.
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R.Reutzel,
S.K.Boehlein,
L.Govindasamy,
R.B.Brenes,
M.Agbandje-McKenna,
S.M.Schuster,
and
R.McKenna
(2002).
Crystallization and preliminary X-ray analysis of the tumor metastasis factor p37.
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Acta Crystallogr D Biol Crystallogr,
58,
2141-2144.
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D.Peters,
and
J.Peters
(2001).
The pseudomolecule method and the structure of globular proteins. II. The example of ribonuclease F1 and T1.
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Biopolymers,
59,
402-410.
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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.
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Int J Biochem Cell Biol,
32,
373-384.
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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.
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Eur J Biochem,
259,
275-280.
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O.Carugo,
and
P.Argos
(1999).
Reliability of atomic displacement parameters in protein crystal structures.
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Acta Crystallogr D Biol Crystallogr,
55,
473-478.
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A.R.Khan,
and
M.N.James
(1998).
Molecular mechanisms for the conversion of zymogens to active proteolytic enzymes.
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Protein Sci,
7,
815-836.
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M.E.McGrath,
J.T.Palmer,
D.Brömme,
and
J.R.Somoza
(1998).
Crystal structure of human cathepsin S.
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Protein Sci,
7,
1294-1302.
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D.A.Giegel
(1997).
ICE processing and kinetic mechanism.
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J Cell Biochem,
64,
11-18.
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R.Tikkanen,
M.Peltola,
C.Oinonen,
J.Rouvinen,
and
L.Peltonen
(1997).
Several cooperating binding sites mediate the interaction of a lysosomal enzyme with phosphotransferase.
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EMBO J,
16,
6684-6693.
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S.A.Gillmor,
C.S.Craik,
and
R.J.Fletterick
(1997).
Structural determinants of specificity in the cysteine protease cruzain.
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Protein Sci,
6,
1603-1611.
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PDB codes:
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D.Maes,
J.Bouckaert,
F.Poortmans,
L.Wyns,
and
Y.Looze
(1996).
Structure of chymopapain at 1.7 A resolution.
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Biochemistry,
35,
16292-16298.
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PDB code:
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M.Cygler,
J.Sivaraman,
P.Grochulski,
R.Coulombe,
A.C.Storer,
and
J.S.Mort
(1996).
Structure of rat procathepsin B: model for inhibition of cysteine protease activity by the proregion.
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Structure,
4,
405-416.
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PDB codes:
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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
codes are
shown on the right.
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Links
