Role of ser-237 in the Substrate Specificity of the Carbapenem-Hydrolyzing Class A Beta-Lactamase Sme-1

Biochim Biophys Acta. 1999 Aug 17;1433(1-2):153-8. doi: 10.1016/s0167-4838(99)00138-7.

Abstract

The role of the serine residue found at position 237 in the carbapenemase Sme-1 has been investigated by constructing a mutant in which Ser-237 was replaced by an alanine. The S237A mutant showed a catalytic behavior against penicillins and aztreonam very similar to that of Sme-1. By contrast, S237A was characterized by a reduced catalytic efficiency against cephems, such as cephalothin and cephaloridine. In addition, the weak activity of Sme-1 against the cephamycin cefoxitin was hardly detectable with the mutant enzyme. Finally, the Ser-237-->Ala mutation resulted in a marked decrease in catalytic activity against imipenem, showing that Ser-237 contributes to the carbapenemase activity of the class A beta-lactamase Sme-1.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine / chemistry
  • Carbapenems / chemistry*
  • Carbapenems / metabolism
  • Carbapenems / pharmacology
  • Enterobacteriaceae / enzymology*
  • Enterobacteriaceae / genetics
  • Escherichia coli / drug effects
  • Escherichia coli / metabolism
  • Hydrolysis
  • Imipenem / metabolism
  • Mutagenesis, Site-Directed
  • Mutation
  • Serine / chemistry*
  • Substrate Specificity
  • beta-Lactam Resistance
  • beta-Lactamases / chemistry*
  • beta-Lactamases / genetics
  • beta-Lactamases / metabolism

Substances

  • Carbapenems
  • Serine
  • Imipenem
  • beta-lactamase Sme-1
  • beta-Lactamases
  • beta-lactamase TEM-1
  • Alanine