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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
8
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pubmed:dateCreated |
1996-9-23
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pubmed:abstractText |
The structure of the plasmid-mediated beta-lactamase TEM-1 has been solved in complex with a designed boronic acid inhibitor (1R)-1-acetamido-2-(3-carboxyphenyl)ethane boronic acid at 1.7 A resolution. The boronate inhibitor was designed based on the crystallographic coordinates of the acyl-enzyme intermediate of TEM-1 bound to the substrate penicillin G. The boronate-TEM-1 complex is highly ordered and defines a novel transition state analogue of the deacylation step in the beta-lactamase reaction pathway. The design principles of this highly effective inhibitor (Ki = 110 nM) and the resulting structural and mechanistic implications are presented.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1072-8368
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
3
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
688-95
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pubmed:dateRevised |
2008-8-22
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pubmed:meshHeading |
pubmed-meshheading:8756327-Acetamides,
pubmed-meshheading:8756327-Binding Sites,
pubmed-meshheading:8756327-Boronic Acids,
pubmed-meshheading:8756327-Crystallography,
pubmed-meshheading:8756327-Drug Design,
pubmed-meshheading:8756327-Enzyme Inhibitors,
pubmed-meshheading:8756327-Hydrogen Bonding,
pubmed-meshheading:8756327-Models, Chemical,
pubmed-meshheading:8756327-Models, Molecular,
pubmed-meshheading:8756327-Molecular Mimicry,
pubmed-meshheading:8756327-Penicillin G,
pubmed-meshheading:8756327-beta-Lactamases
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pubmed:year |
1996
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pubmed:articleTitle |
Structure-based design of a potent transition state analogue for TEM-1 beta-lactamase.
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pubmed:affiliation |
Department of Biochemistry, University of Alberta, Edmonton, Canada.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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