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PDBsum entry 1blc
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Hydrolase(acting in cyclic amides)
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PDB id
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1blc
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References listed in PDB file
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Key reference
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Title
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Inhibition of beta-Lactamase by clavulanate. Trapped intermediates in cryocrystallographic studies.
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Authors
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C.C.Chen,
O.Herzberg.
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Ref.
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J Mol Biol, 1992,
224,
1103-1113.
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PubMed id
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Abstract
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Crystallographic studies of the complex between beta-lactamase and clavulanate
reveal a structure of two acyl-enzymes with covalent bonds at the active site
Ser70, representing two different stages of inhibitor degradation alternately
occupying the active site. Models that are consistent with biochemical data are
derived from the electron density map and refined at 2.2 A resolution: cis
enamine, in which the carboxylate group of the clavulanate molecule makes a salt
bridge with Lys234 of beta-lactamase; decarboxylated trans enamine, which is
oriented away from Lys234. For both acyl-enzymes, the carbonyl oxygen atom of
the ester group occupies the oxyanion hole in a manner similar to that found in
inhibitor binding to serine proteases. Whereas the oxygen atom in the trans
product is optimally positioned in the oxyanion hole, that of the cis product
clashes with the main-chain nitrogen atom of Ser70 and the beta-carbon atom of
the adjacent Ala69. In contrast to cis to trans isomerization in solution that
relieves the steric strain inherent in a cis double bond, at the
enzyme-inhibitor interface two additional factors play an important role. The
salt bridge enhances the stability of the cis product, while the steric strain
introduced by the short contacts with the protein reduces its stability.
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Secondary reference #1
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Title
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Structure of a phosphonate-Inhibited beta-Lactamase. An analog of the tetrahedral transition state/intermediate of beta-Lactam hydrolysis.
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Authors
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C.C.Chen,
J.Rahil,
R.F.Pratt,
O.Herzberg.
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Ref.
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J Mol Biol, 1993,
234,
165-178.
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PubMed id
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Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
perfect match.
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Secondary reference #2
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Title
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Refined crystal structure of beta-Lactamase from staphylococcus aureus pc1 at 2.0 a resolution.
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Author
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O.Herzberg.
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Ref.
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J Mol Biol, 1991,
217,
701-719.
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PubMed id
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Secondary reference #3
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Title
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Structural basis for the inactivation of the p54 mutant of beta-Lactamase from staphylococcus aureus pc1.
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Authors
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O.Herzberg,
G.Kapadia,
B.Blanco,
T.S.Smith,
A.Coulson.
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Ref.
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Biochemistry, 1991,
30,
9503-9509.
[DOI no: ]
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PubMed id
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Secondary reference #4
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Title
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Penicillin-Binding and degrading enzymes
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Authors
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O.Herzberg,
J.Moult.
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Ref.
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curr opin struct biol, 1991,
1,
946.
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Secondary reference #5
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Title
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Bacterial resistance to beta-Lactam antibiotics: crystal structure of beta-Lactamase from staphylococcus aureus pc1 at 2.5 a resolution.
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Authors
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O.Herzberg,
J.Moult.
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Ref.
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Science, 1987,
236,
694-701.
[DOI no: ]
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PubMed id
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Secondary reference #6
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Title
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The crystal structure of beta-Lactamase from staphylococcus aureus at 0.5 nm resolution.
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Authors
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J.Moult,
L.Sawyer,
O.Herzberg,
C.L.Jones,
A.F.Coulson,
D.W.Green,
M.M.Harding,
R.P.Ambler.
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Ref.
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Biochem J, 1985,
225,
167-176.
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PubMed id
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