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PDBsum entry 1ke2
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Hydrolase/hydrolase inhibitor
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PDB id
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1ke2
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Inhibitor complexes of the pseudomonas serine-Carboxyl proteinase.
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Authors
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A.Wlodawer,
M.Li,
A.Gustchina,
Z.Dauter,
K.Uchida,
H.Oyama,
N.E.Goldfarb,
B.M.Dunn,
K.Oda.
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Ref.
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Biochemistry, 2001,
40,
15602-15611.
[DOI no: ]
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PubMed id
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Abstract
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Crystal structures of the serine-carboxyl proteinase from Pseudomonas sp. 101
(PSCP), complexed with a number of inhibitors, have been solved and refined at
high- to atomic-level resolution. All of these inhibitors (tyrostatin,
pseudo-tyrostatin, AcIPF, AcIAF, and chymostatin, as well as previously studied
iodotyrostatin and pseudo-iodotyrostatin) make covalent bonds to the active site
Ser287 through their aldehyde moieties, while their side chains occupy subsites
S1-S4 of the enzyme. The mode of binding of the inhibitors is almost identical
for their P1 and P2 side chains, while significant differences are observed for
P3 and P4 (if present). Kinetic parameters for the binding of these nanomolar
inhibitors to PSCP have been established and correlated with the observed mode
of binding. The preferences of this enzyme for a larger side chain in P2 as well
as Tyr or Phe in P1 are explained by the size, shape, and characteristics of the
S2 and S1 regions of the protein structure, respectively. Networks of hydrogen
bonds involving glutamic and aspartic acids have been analyzed for the
atomic-resolution structure of the native enzyme. PSCP contains a
calcium-binding site that consists of Asp328, Asp348, three amide carbonyl
groups, and a water molecule, in almost perfect octahedral coordination. The
presence of Ca(2+) cation is necessary for the activity of the enzyme.
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