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
Author Information
Ram Prasad Bhusal: School of Chemical Sciences, The University of Auckland, Private Bag 92019, Victoria Street West, Auckland, 1142, New Zealand. ORCID
Wanting Jiao: Ferrier Research Institute, Victoria University of Wellington, PO Box 600, Wellington, 6140, New Zealand. ORCID
Brooke X C Kwai: School of Chemical Sciences, The University of Auckland, Private Bag 92019, Victoria Street West, Auckland, 1142, New Zealand. ORCID
Jóhannes Reynisson: School of Chemical Sciences, The University of Auckland, Private Bag 92019, Victoria Street West, Auckland, 1142, New Zealand. ORCID
Annabelle J Collins: School of Chemical Sciences, The University of Auckland, Private Bag 92019, Victoria Street West, Auckland, 1142, New Zealand. ORCID
Jonathan Sperry: School of Chemical Sciences, The University of Auckland, Private Bag 92019, Victoria Street West, Auckland, 1142, New Zealand. j.sperry@auckland.ac.nz. ORCID
Ghader Bashiri: Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Private Bag 92019, Victoria Street West, Auckland, 1142, New Zealand. g.bashiri@auckland.ac.nz. ORCID
Ivanhoe K H Leung: School of Chemical Sciences, The University of Auckland, Private Bag 92019, Victoria Street West, Auckland, 1142, New Zealand. i.leung@auckland.ac.nz. ORCID
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.
