Beta-lactamase inactivation by mechanism-based reagents.

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

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

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
Volume289
Issue number1036
StatePublished - May 16 1980
Externally publishedYes

Fingerprint

beta-lactamase
beta-Lactamases
inactivation
enzyme
Sulfones
Enzymes
enzymes
chemical derivatives
Derivatives
Cefoxitin
beta-lactams
beta acids
enzyme substrates
Enzyme activity
beta-Lactams
Escherichia coli
enzyme activity
hydrolysis
Hydrolysis
mechanism of action

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Agricultural and Biological Sciences (miscellaneous)

Cite this

Beta-lactamase inactivation by mechanism-based reagents. / Fisher, J.; Belasco, J. G.; Charnas, R. L.; Khosla, Sundeep; Knowles, J. R.

In: Philosophical transactions of the Royal Society of London. Series B: Biological sciences, Vol. 289, No. 1036, 16.05.1980, p. 309-319.

Research output: Contribution to journalArticle

Fisher, J. ; Belasco, J. G. ; Charnas, R. L. ; Khosla, Sundeep ; Knowles, J. R. / Beta-lactamase inactivation by mechanism-based reagents. In: Philosophical transactions of the Royal Society of London. Series B: Biological sciences. 1980 ; Vol. 289, No. 1036. pp. 309-319.
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