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

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...

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Autores principales: Bhusal, Ram Prasad, Jiao, Wanting, Kwai, Brooke X. C., Reynisson, Jóhannes, Collins, Annabelle J., Sperry, Jonathan, Bashiri, Ghader, Leung, Ivanhoe K. H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6788997/
https://www.ncbi.nlm.nih.gov/pubmed/31604954
http://dx.doi.org/10.1038/s41467-019-12614-7
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author Bhusal, Ram Prasad
Jiao, Wanting
Kwai, Brooke X. C.
Reynisson, Jóhannes
Collins, Annabelle J.
Sperry, Jonathan
Bashiri, Ghader
Leung, Ivanhoe K. H.
author_facet Bhusal, Ram Prasad
Jiao, Wanting
Kwai, Brooke X. C.
Reynisson, Jóhannes
Collins, Annabelle J.
Sperry, Jonathan
Bashiri, Ghader
Leung, Ivanhoe K. H.
author_sort Bhusal, Ram Prasad
collection PubMed
description 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.
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spelling pubmed-67889972019-10-15 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. Nat Commun Article 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. Nature Publishing Group UK 2019-10-11 /pmc/articles/PMC6788997/ /pubmed/31604954 http://dx.doi.org/10.1038/s41467-019-12614-7 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
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
title Acetyl-CoA-mediated activation of Mycobacterium tuberculosis isocitrate lyase 2
title_full Acetyl-CoA-mediated activation of Mycobacterium tuberculosis isocitrate lyase 2
title_fullStr Acetyl-CoA-mediated activation of Mycobacterium tuberculosis isocitrate lyase 2
title_full_unstemmed Acetyl-CoA-mediated activation of Mycobacterium tuberculosis isocitrate lyase 2
title_short Acetyl-CoA-mediated activation of Mycobacterium tuberculosis isocitrate lyase 2
title_sort acetyl-coa-mediated activation of mycobacterium tuberculosis isocitrate lyase 2
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6788997/
https://www.ncbi.nlm.nih.gov/pubmed/31604954
http://dx.doi.org/10.1038/s41467-019-12614-7
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