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Acetyl-CoA-mediated activation of Mycobacterium tuberculosis isocitrate lyase 2

Reynisson

Acetyl-CoA-mediated activation of Mycobacterium tuberculosis isocitrate lyase 2 Thumbnail


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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.

Acceptance Date Sep 18, 2019
Publication Date Oct 11, 2019
Publicly Available Date Mar 28, 2024
Journal Nature Communications
Print ISSN 2041-1723
Pages 4639 - ?
DOI https://doi.org/10.1038/s41467-019-12614-7
Keywords Biochemistry, Enzyme mechanisms, SAXS, X-ray crystallography
Publisher URL http://doi.org/10.1038/s41467-019-12614-7

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