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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
Nature communications | 2019

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.

Pubmed ID: 31604954

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