Use of novel boronic acid transition state inhibitors to probe substrate affinity in SHV-type extended-spectrum beta-lactamases

Antimicrob Agents Chemother. 2007 Apr;51(4):1577-9. doi: 10.1128/AAC.01293-06. Epub 2007 Jan 12.

Abstract

Boronic acid transition state inhibitors (BATSIs) with R1 side chains of cefotaxime and ceftazidime were assayed against SHV-1, SHV-2, SHV-5, D104K, and D104K G238S beta-lactamases. The D104K variant was the most susceptible to inhibition by the ceftazidime BATSI (Ki, 730+/-80 nM), while the D104K G238S variant was the most susceptible to the cefotaxime BATSI (Ki, 1.1+/-0.2 microM).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Boronic Acids / pharmacology*
  • Ceftazidime / pharmacology
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Substrate Specificity
  • beta-Lactamase Inhibitors*
  • beta-Lactamases / drug effects
  • beta-Lactamases / metabolism

Substances

  • Anti-Bacterial Agents
  • Boronic Acids
  • Enzyme Inhibitors
  • beta-Lactamase Inhibitors
  • Ceftazidime
  • beta-Lactamases