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bioRxiv · 10.64898/2026.04.08.716820

Time-resolved cryo-EM reveals conformational trajectory of allosteric activation in isocitrate lyase

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.
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Abstract

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.

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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.. 2026-04-09. Time-resolved cryo-EM reveals conformational trajectory of allosteric activation in isocitrate lyase. https://doi.org/10.64898/2026.04.08.716820

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