Acetyl-CoA-mediated activation of Mycobacterium tuberculosis isocitrate lyase 2

Nat Commun. 2019 Oct 11;10(1):4639. doi: 10.1038/s41467-019-12614-7.

Abstract

Isocitrate lyase is important for lipid utilisation by Mycobacterium tuberculosis but its ICL2 isoform is poorly understood. Here we report that binding of the lipid metabolites acetyl-CoA or propionyl-CoA to ICL2 induces a striking structural rearrangement, substantially increasing isocitrate lyase and methylisocitrate lyase activities. Thus, ICL2 plays a pivotal role regulating carbon flux between the tricarboxylic acid (TCA) cycle, glyoxylate shunt and methylcitrate cycle at high lipid concentrations, a mechanism essential for bacterial growth and virulence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyl Coenzyme A / metabolism*
  • Acetyl Coenzyme A / physiology
  • Acyl Coenzyme A / metabolism
  • Carbon / metabolism
  • Citric Acid Cycle
  • Crystallography, X-Ray
  • Isocitrate Lyase / chemistry
  • Isocitrate Lyase / metabolism*
  • Lipid Metabolism
  • Magnetic Resonance Spectroscopy
  • Molecular Docking Simulation
  • Mycobacterium tuberculosis / enzymology*
  • Protein Domains

Substances

  • Acyl Coenzyme A
  • propionyl-coenzyme A
  • Acetyl Coenzyme A
  • Carbon
  • Isocitrate Lyase