Structural insights into Escherichia coli phosphopantothenoylcysteine synthetase by native ion mobility-mass spectrometry

Biochem J. 2019 Nov 15;476(21):3125-3139. doi: 10.1042/BCJ20190318.

Abstract

CoaBC, part of the vital coenzyme A biosynthetic pathway in bacteria, has recently been validated as a promising antimicrobial target. In this work, we employed native ion mobility-mass spectrometry to gain structural insights into the phosphopantothenoylcysteine synthetase domain of E. coli CoaBC. Moreover, native mass spectrometry was validated as a screening tool to identify novel inhibitors of this enzyme, highlighting the utility and versatility of this technique both for structural biology and for drug discovery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carboxy-Lyases / antagonists & inhibitors
  • Carboxy-Lyases / chemistry*
  • Carboxy-Lyases / metabolism
  • Dimerization
  • Drug Evaluation, Preclinical / methods*
  • Enzyme Inhibitors / chemistry
  • Escherichia coli / chemistry
  • Escherichia coli / drug effects
  • Escherichia coli / enzymology*
  • Escherichia coli / genetics
  • Escherichia coli Proteins / antagonists & inhibitors
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / metabolism
  • Kinetics
  • Mass Spectrometry / methods*
  • Multienzyme Complexes / antagonists & inhibitors
  • Multienzyme Complexes / chemistry*
  • Multienzyme Complexes / metabolism
  • Peptide Synthases / antagonists & inhibitors
  • Peptide Synthases / chemistry*
  • Peptide Synthases / metabolism
  • Protein Domains

Substances

  • Dfp protein, E coli
  • Enzyme Inhibitors
  • Escherichia coli Proteins
  • Multienzyme Complexes
  • Carboxy-Lyases
  • Peptide Synthases