Class B Beta-Lactamases: The Importance of Being Metallic

Curr Pharm Des. 1999 Nov;5(11):915-27.

Abstract

The structural and functional features of class B b-lactamases, which are metal-dependent, are reviewed in this article. Enzymes from different bacterial strains exhibit a common fold and sequence similarity in their active sites. However, the protein scaffold fine tunes the metal binding affinity and substrate selectivity. In this way, some metallo-b-lactamases seem to be functional with only one Zn(II) equivalent per enzyme, whereas others require a binuclear active site. The sequence similarity leads to a subdivision of these enzymes into three subclasses. The substrate specificities are rather broad, except for enzymes belonging to subclass B2. Some inhibitors have been designed and tested, but none of them is able to exhibit a broad spectrum against these enzymes.

Publication types

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

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Base Sequence
  • Binding Sites
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Hydrolysis
  • Metalloproteins / antagonists & inhibitors*
  • Metalloproteins / chemistry*
  • Metalloproteins / classification
  • Models, Molecular
  • Molecular Sequence Data
  • Zinc / chemistry*
  • beta-Lactamase Inhibitors*
  • beta-Lactamases / chemistry*
  • beta-Lactamases / classification
  • beta-Lactams

Substances

  • Anti-Bacterial Agents
  • Enzyme Inhibitors
  • Metalloproteins
  • beta-Lactamase Inhibitors
  • beta-Lactams
  • beta-Lactamases
  • Zinc