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PDBsum entry 1ms6
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Contents |
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* Residue conservation analysis
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PDB id:
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Hydrolase
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Title:
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Dipeptide nitrile inhibitor bound to cathepsin s.
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Structure:
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Cathepsin s. Chain: a. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562
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Resolution:
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1.90Å
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R-factor:
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0.155
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R-free:
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0.197
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Authors:
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Y.D.Ward,D.S.Thomson,L.L.Frye,C.L.Cywin,T.Morwick,M.J.Emmanuel, R.Zindell,D.Mcneil,Y.Bekkali,M.Giradot,M.Hrapchak,M.Deturi,K.Crane, D.White,S.Pav,Y.Wang,M.H.Hao,C.A.Grygon,M.E.Labadia,D.M.Freeman, W.Davidson,J.L.Hopkins,M.L.Brown,D.M.Spero
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Key ref:
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Y.D.Ward
et al.
(2002).
Design and synthesis of dipeptide nitriles as reversible and potent Cathepsin S inhibitors.
J Med Chem,
45,
5471-5482.
PubMed id:
DOI:
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Date:
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19-Sep-02
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Release date:
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22-Apr-03
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PROCHECK
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Headers
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References
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P25774
(CATS_HUMAN) -
Cathepsin S from Homo sapiens
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Seq:
Struc:
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331 a.a.
217 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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Enzyme class:
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E.C.3.4.22.27
- cathepsin S.
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Reaction:
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Similar to cathepsin L, but with much less activity on Z-Phe-Arg-|-NHMec, and more activity on the Z-Val-Val-Arg-|-Xaa compound.
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DOI no:
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J Med Chem
45:5471-5482
(2002)
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PubMed id:
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Design and synthesis of dipeptide nitriles as reversible and potent Cathepsin S inhibitors.
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Y.D.Ward,
D.S.Thomson,
L.L.Frye,
C.L.Cywin,
T.Morwick,
M.J.Emmanuel,
R.Zindell,
D.McNeil,
Y.Bekkali,
M.Girardot,
M.Hrapchak,
M.DeTuri,
K.Crane,
D.White,
S.Pav,
Y.Wang,
M.H.Hao,
C.A.Grygon,
M.E.Labadia,
D.M.Freeman,
W.Davidson,
J.L.Hopkins,
M.L.Brown,
D.M.Spero,
M.Giradot.
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ABSTRACT
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The specificity of the immune response relies on processing of foreign proteins
and presentation of antigenic peptides at the cell surface. Inhibition of
antigen presentation, and the subsequent activation of T-cells, should, in
theory, modulate the immune response. The cysteine protease Cathepsin S performs
a fundamental step in antigen presentation and therefore represents an
attractive target for inhibition. Herein, we report a series of potent and
reversible Cathepsin S inhibitors based on dipeptide nitriles. These inhibitors
show nanomolar inhibition of the target enzyme as well as cellular potency in a
human B cell line. The first X-ray crystal structure of a reversible inhibitor
cocrystallized with Cathepsin S is also reported.
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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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K.Steert,
M.Berg,
J.C.Mottram,
G.D.Westrop,
G.H.Coombs,
P.Cos,
L.Maes,
J.Joossens,
P.Van der Veken,
A.Haemers,
and
K.Augustyns
(2010).
α-ketoheterocycles as inhibitors of Leishmania mexicana cysteine protease CPB.
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ChemMedChem,
5,
1734-1748.
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R.Löser,
J.Gut,
P.J.Rosenthal,
M.Frizler,
M.Gütschow,
and
K.T.Andrews
(2010).
Antimalarial activity of azadipeptide nitriles.
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Bioorg Med Chem Lett,
20,
252-255.
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A.W.Schüttelkopf,
G.Hamilton,
C.Watts,
and
D.M.van Aalten
(2006).
Structural basis of reduction-dependent activation of human cystatin F.
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J Biol Chem,
281,
16570-16575.
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PDB code:
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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.
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Protein Sci,
15,
2619-2629.
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PDB code:
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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
code is
shown on the right.
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Links
