A minimalistic approach to identify substrate binding features in B1 Metallo-beta-lactamases

Bioorg Med Chem Lett. 2007 Sep 15;17(18):5171-4. doi: 10.1016/j.bmcl.2007.06.089. Epub 2007 Jul 5.

Abstract

The 2-oxoazetidinylacetate sodium salt was synthesized as a model of a minimal beta-lactam drug. This compound and the monobactam aztreonam were assayed as substrates of the Metallo-beta-lactamase BcII. None of them was hydrolyzed by the enzyme. While the azetidinone was not able to bind BcII, aztreonam was shown to bind in a nonproductive mode. These results provide an explanation for the unability of Metallo-beta-lactamases to inactive monobactams and give some clues for inhibitor design.

MeSH terms

  • Magnetic Resonance Spectroscopy
  • Spectrometry, Fluorescence
  • Spectrophotometry, Ultraviolet
  • Substrate Specificity
  • beta-Lactamases / metabolism*

Substances

  • beta-Lactamases