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Bhusal, RP, Jiao, W, Kwai, BXC, Reynisson, J, Collins, AJ, Sperry, J, Bashiri, G and Leung, IKH (2019) Acetyl-CoA-mediated activation of Mycobacterium tuberculosis isocitrate lyase 2. Nature Communications, 10 (1). 4639 - ?. ISSN 2041-1723

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Abstract

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.

Item Type: Article
Additional Information: This is the final published version of the article (version of record). It first appeared online via Springer Nature at https://doi.org/10.1038/s41467-019-12614-7 - please refer to any applicable terms of use of the publisher.
Uncontrolled Keywords: Biochemistry, Enzyme mechanisms, SAXS, X-ray crystallography
Subjects: R Medicine > RS Pharmacy and materia medica
Divisions: Faculty of Medicine and Health Sciences > School of Pharmacy and Bioengineering
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Depositing User: Symplectic
Date Deposited: 28 Oct 2019 12:13
Last Modified: 28 Oct 2019 12:19
URI: https://eprints.keele.ac.uk/id/eprint/7095

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