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

Ram Prasad Bhusal, Wanting Jiao, Brooke X.C. Kwai, Jóhannes Reynisson, Annabelle J. Collins, Jonathan Sperry, Ghader Bashiri, Ivanhoe K.H. Leung

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Article number4639
Number of pages7
JournalNature Communications
Volume10
Issue number1
DOIs
Publication statusPublished - 11 Oct 2019
Externally publishedYes

Keywords

  • biochemistry
  • enzyme mechanisms
  • SAXS
  • x-ray crystallography

Cite this

Bhusal, R. P., Jiao, W., Kwai, B. X. C., Reynisson, J., Collins, A. J., Sperry, J., ... Leung, I. K. H. (2019). Acetyl-CoA-mediated activation of Mycobacterium tuberculosis isocitrate lyase 2. Nature Communications, 10(1), [4639]. https://doi.org/10.1038/s41467-019-12614-7
Bhusal, Ram Prasad ; Jiao, Wanting ; Kwai, Brooke X.C. ; Reynisson, Jóhannes ; Collins, Annabelle J. ; Sperry, Jonathan ; Bashiri, Ghader ; Leung, Ivanhoe K.H. / Acetyl-CoA-mediated activation of Mycobacterium tuberculosis isocitrate lyase 2. In: Nature Communications. 2019 ; Vol. 10, No. 1.
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Bhusal, RP, Jiao, W, Kwai, BXC, Reynisson, J, Collins, AJ, Sperry, J, Bashiri, G & Leung, IKH 2019, 'Acetyl-CoA-mediated activation of Mycobacterium tuberculosis isocitrate lyase 2', Nature Communications, vol. 10, no. 1, 4639. https://doi.org/10.1038/s41467-019-12614-7

Acetyl-CoA-mediated activation of Mycobacterium tuberculosis isocitrate lyase 2. / Bhusal, Ram Prasad; Jiao, Wanting; Kwai, Brooke X.C.; Reynisson, Jóhannes; Collins, Annabelle J.; Sperry, Jonathan; Bashiri, Ghader; Leung, Ivanhoe K.H.

In: Nature Communications, Vol. 10, No. 1, 4639, 11.10.2019.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Acetyl-CoA-mediated activation of Mycobacterium tuberculosis isocitrate lyase 2

AU - Bhusal, Ram Prasad

AU - Jiao, Wanting

AU - Kwai, Brooke X.C.

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AU - Collins, Annabelle J.

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AU - Leung, Ivanhoe K.H.

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