Taka, J.; Jung, J.; Guo, S.; Jiao, W.; Kwai, B. X.; de Carvalho, L.; McNeil, M.; Huang, E. Y.; Yu, Z.; Leung, I. K. H.; Bashiri, G.

Isocitrate lyase 2 (ICL2) from Mycobacterium tuberculosis undergoes dramatic conformational rearrangements upon binding to the allosteric effector acetyl-CoA. Time resolved cryo EM captured conformational states along the ICL2 activation trajectory, revealing how acetyl CoA binding at the allosteric sites leads to asymmetric, half-of-site activity at the catalytic centres. These findings support a conformational selection model of allostery, whereby acetyl-CoA binding shifts the pre-existing equilibrium towards an active state of the enzyme.