Abstract
The interaction of representative beta-lactam antibiotics with a bacterial enzyme target has been mapped in three dimensions using X-ray diffraction data to 2.25 A resolution. Examination of complexes of cephalosporin C, benzylmonobactam, and alpha-(2,3)-methylenepenicillin G with the D-alanyl-D-alanine transpeptidase-carboxypeptidase from Streptomyces R61 shows that the enzyme's reactive serine has acylated the beta-lactam ring of each inhibitor. The known half-lives of the three acyl complexes can be correlated with the distance of the drug's carboxylate (or sulfonate) group from complementary groups on the DD-peptidase.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Anti-Bacterial Agents / chemistry
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Anti-Bacterial Agents / metabolism*
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Cephalosporins / chemistry
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Cephalosporins / metabolism
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Models, Molecular*
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Monobactams / chemistry
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Monobactams / metabolism
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Muramoylpentapeptide Carboxypeptidase / chemistry
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Muramoylpentapeptide Carboxypeptidase / metabolism*
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Penicillin G / analogs & derivatives
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Penicillin G / chemistry
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Penicillin G / metabolism
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Streptomyces / enzymology*
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X-Ray Diffraction
Substances
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Anti-Bacterial Agents
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Cephalosporins
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Monobactams
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2,3-methylene penam
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cephalosporin C
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benzylmonobactam
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Muramoylpentapeptide Carboxypeptidase
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Penicillin G