Structural insights into the design of reversible fluorescent probes for metallo-β-lactamases NDM-1, VIM-2, and IMP-1

J Inorg Biochem. 2022 Aug:233:111869. doi: 10.1016/j.jinorgbio.2022.111869. Epub 2022 May 20.

Abstract

Metallo-β-lactamases (MBLs) are enzymes that are capable of hydrolyzing most β-lactam antibiotics and all clinically relevant carbapenems. We developed a library of reversible fluorescent turn-on probes that are designed to directly bind to the dizinc active site of these enzymes and can be used to study their dynamic metalation state and enzyme-inhibitor interactions. Structure-function relationships with regards to inhibitory strength and fluorescence turn-on response were evaluated for three representative MBLs.

Keywords: Antibiotic resistance; Fluorescent probe; Metalloenzyme inhibitor.

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 / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Fluorescent Dyes*
  • beta-Lactamase Inhibitors* / chemistry
  • beta-Lactamase Inhibitors* / pharmacology
  • beta-Lactamases / metabolism

Substances

  • Anti-Bacterial Agents
  • beta-Lactamase Inhibitors
  • beta-lactamase NDM-1
  • beta-Lactamases
  • Fluorescent Dyes