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

Ram Prasad Bhusal, Wanting Jiao, Brooke X.C. Kwai, Jóhannes Reynisson, Annabelle J. Collins, Jonathan Sperry, Ghader Bashiri, Ivanhoe K.H. Leung

Research output: Contribution to journalArticleResearchpeer-review

3 Citations (Scopus)

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.

Original languageEnglish
Article number4639
Number of pages7
JournalNature Communications
Volume10
Issue number1
DOIs
Publication statusPublished - 11 Oct 2019
Externally publishedYes

Keywords

  • biochemistry
  • enzyme mechanisms
  • SAXS
  • x-ray crystallography

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