Complete ¹H, ¹⁵N, and ¹³C resonance assignments of Bacillus cereus metallo-β-lactamase and its complex with the inhibitor R-thiomandelic acid

Biomol NMR Assign. 2014 Oct;8(2):313-8. doi: 10.1007/s12104-013-9507-1. Epub 2013 Jul 10.

Abstract

β-Lactamases inactivate β-lactam antibiotics by hydrolysis of their endocyclic β-lactam bond and are a major cause of antibiotic resistance in pathogenic bacteria. The zinc dependent metallo-β-lactamase enzymes are of particular concern since they are located on highly transmissible plasmids and have a broad spectrum of activity against almost all β-lactam antibiotics. We present here essentially complete (>96%) backbone and sidechain sequence-specific NMR resonance assignments for the Bacillus cereus subclass B1 metallo-β-lactamase, BcII, and for its complex with R-thiomandelic acid, a broad spectrum inhibitor of metallo-β-lactamases. These assignments have been used as the basis for determination of the solution structures of the enzyme and its inhibitor complex and can also be used in a rapid screen for other metallo-β-lactamase inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacillus cereus / enzymology*
  • Mandelic Acids / metabolism*
  • Mandelic Acids / pharmacology*
  • Nuclear Magnetic Resonance, Biomolecular*
  • Sulfhydryl Compounds / metabolism*
  • Sulfhydryl Compounds / pharmacology*
  • beta-Lactamase Inhibitors / metabolism
  • beta-Lactamase Inhibitors / pharmacology
  • beta-Lactamases / chemistry*
  • beta-Lactamases / metabolism*

Substances

  • Mandelic Acids
  • Sulfhydryl Compounds
  • beta-Lactamase Inhibitors
  • thiomandelic acid
  • beta-Lactamases