ESI-MS assay of M. tuberculosis cell wall antigen 85 enzymes permits substrate profiling and design of a mechanism-based inhibitor

J Am Chem Soc. 2011 Aug 31;133(34):13232-5. doi: 10.1021/ja204249p. Epub 2011 Aug 9.

Abstract

Mycobacterium tuberculosis Antigen 85 enzymes are vital to the integrity of the highly impermeable cell envelope and are potential therapeutic targets. Kinetic analysis using a label-free assay revealed both mechanistic details and a substrate profile that allowed the design and construction of a selective in vitro mechanism-based inhibitor.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyltransferases / antagonists & inhibitors*
  • Acyltransferases / metabolism
  • Antigens, Bacterial / metabolism
  • Antitubercular Agents / chemistry*
  • Antitubercular Agents / pharmacology*
  • Bacterial Proteins / antagonists & inhibitors
  • Bacterial Proteins / metabolism
  • Drug Design
  • Humans
  • Models, Molecular
  • Mycobacterium tuberculosis / drug effects
  • Mycobacterium tuberculosis / enzymology*
  • Spectrometry, Mass, Electrospray Ionization / methods*
  • Tuberculosis / drug therapy

Substances

  • Antigens, Bacterial
  • Antitubercular Agents
  • Bacterial Proteins
  • Acyltransferases
  • antigen 85A, Mycobacterium tuberculosis
  • antigen 85B, Mycobacterium tuberculosis
  • antigen 85C, Mycobacterium tuberculosis