Beta-lactamase inactivation by mechanism-based reagents.

J. Fisher, J. G. Belasco, R. L. Charnas, S. Khosla, J. R. Knowles

Research output: Contribution to journalArticlepeer-review

57 Scopus citations


The mechanistic pathway followed by the E. coli RTEM beta-lactamase has been studied with a view to clarifying the mode of action of a number of recently discovered inactivators of the enzyme. There is clear evidence that the beta-lactamase-catalysed hydrolysis of the 7-alpha-methoxycephem, cefoxitin, proceeds via an acyl-enzyme intermediate. An analysis of the inactivation reactions of all the known beta-lactam derivatives that result in irreversible loss of enzyme activity permits the identification of three structural features required for a beta-lactamase inactivator. The application of these principles suggests a new group of mechanism-based inactivators of the enzyme: the sulphones of N-acyl derivatives of 6-beta-aminopenicillanic acid that are themselves poor substrates for the enzyme. These sulphones are powerful inactivators of the beta-lactamase.

Original languageEnglish (US)
Pages (from-to)309-319
Number of pages11
JournalPhilosophical transactions of the Royal Society of London. Series B, Biological sciences
Issue number1036
StatePublished - May 16 1980

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)


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