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

Reynisson

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.

Citation

Reynisson. (2019). Acetyl-CoA-mediated activation of Mycobacterium tuberculosis isocitrate lyase 2. Nature communications, 4639 - ?. https://doi.org/10.1038/s41467-019-12614-7

• Acceptance Date: Sep 18, 2019
• Publication Date: Oct 11, 2019
• 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