The mutation Lys234His yields a class A beta-lactamase with a novel pH-dependence

Biochem J. 1991 Sep 15;278 ( Pt 3)(Pt 3):673-8. doi: 10.1042/bj2780673.

Abstract

The lysine-234 residue is highly conserved in beta-lactamases and in nearly all active-site-serine penicillin-recognizing enzymes. Its replacement by a histidine residue in the Streptomyces albus G class A beta-lactamase yielded an enzyme the pH-dependence of which was characterized by the appearance of a novel pK, which could be attributed to the newly introduced residue. At low pH, the kcat, value for benzylpenicillin was as high as 50% of that of the wild-type enzyme, demonstrating that an efficient active site was maintained. Both kcat. and kcat/Km dramatically decreased above pH 6 but the decrease in kcat./Km could not be attributed to larger Km values. Thus a positive charge on the side chain of residue 234 appears to be more essential for transition-state stabilization than for initial recognition of the substrate ground state.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ampicillin / metabolism
  • Base Sequence
  • Binding Sites
  • Enzyme Stability
  • Gene Expression
  • Histidine*
  • Hot Temperature
  • Hydrogen-Ion Concentration
  • Hydrolysis
  • Kinetics
  • Lysine*
  • Mutation*
  • Penicillin G / metabolism
  • Streptomyces / enzymology*
  • beta-Lactamases / genetics
  • beta-Lactamases / metabolism*

Substances

  • Histidine
  • Ampicillin
  • beta-Lactamases
  • Lysine
  • Penicillin G