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

doi:10.1038/s41467-019-12614-7

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 journal › Article › Research › peer-review

23 Citations (Scopus)

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 language	English
Article number	4639
Number of pages	7
Journal	Nature Communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-12614-7
Publication status	Published - 11 Oct 2019
Externally published	Yes

Keywords

biochemistry
enzyme mechanisms
SAXS
x-ray crystallography

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/s41467-019-12614-7

286832200-oaFinal published version, 1.28 MB

Cite this

@article{3d508f2f00464194b9ba4ba809268eaa,

title = "Acetyl-CoA-mediated activation of Mycobacterium tuberculosis isocitrate lyase 2",

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.",

keywords = "biochemistry, enzyme mechanisms, SAXS, x-ray crystallography",

author = "Bhusal, {Ram Prasad} and Wanting Jiao and Kwai, {Brooke X.C.} and J{\'o}hannes Reynisson and Collins, {Annabelle J.} and Jonathan Sperry and Ghader Bashiri and Leung, {Ivanhoe K.H.}",

year = "2019",

month = oct,

day = "11",

doi = "10.1038/s41467-019-12614-7",

language = "English",

volume = "10",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

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

AU - Bhusal, Ram Prasad

AU - Jiao, Wanting

AU - Kwai, Brooke X.C.

AU - Reynisson, Jóhannes

AU - Collins, Annabelle J.

AU - Sperry, Jonathan

AU - Bashiri, Ghader

AU - Leung, Ivanhoe K.H.

PY - 2019/10/11

Y1 - 2019/10/11

N2 - 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.

AB - 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.

KW - biochemistry

KW - enzyme mechanisms

KW - SAXS

KW - x-ray crystallography

UR - http://www.scopus.com/inward/record.url?scp=85073146808&partnerID=8YFLogxK

U2 - 10.1038/s41467-019-12614-7

DO - 10.1038/s41467-019-12614-7

M3 - Article

C2 - 31604954

AN - SCOPUS:85073146808

SN - 2041-1723

VL - 10

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 4639

ER -

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

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Cite this