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

Abstract

Isocitrate lyase (ICL) isoforms 1 and 2 are enzymes in the glyoxylate and methylcitrate cycles that enable Mycobacterium tuberculosis (Mtb) to use lipids as a carbon source. Here the authors present the ligand-free Mtb ICL2 and acetyl-CoA bound ICL2 crystal structures, which reveal a structural reorganisation upon acetyl-CoA binding that leads to an activation of its isocitrate lyase and methylcitrate lyase activities.