Allosteric pyruvate kinase-based “logic gate” synergistically senses energy and sugar levels in Mycobacterium tuberculosis

Wenhe Zhong; Liang Cui; Boon Chong Goh; Qixu Cai; Peiying Ho; Yok Hian Chionh; Meng Yuan; Abbas El Sahili; Linda A. Fothergill-Gilmore; Malcolm D. Walkinshaw; Julien Lescar; Peter C. Dedon

doi:10.1038/s41467-017-02086-y

Nature Communications (Dec 2017)

Allosteric pyruvate kinase-based “logic gate” synergistically senses energy and sugar levels in Mycobacterium tuberculosis

Wenhe Zhong,
Liang Cui,
Boon Chong Goh,
Qixu Cai,
Peiying Ho,
Yok Hian Chionh,
Meng Yuan,
Abbas El Sahili,
Linda A. Fothergill-Gilmore,
Malcolm D. Walkinshaw,
Julien Lescar,
Peter C. Dedon

Affiliations

Wenhe Zhong: Infectious Disease Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology
Liang Cui: Infectious Disease Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology
Boon Chong Goh: Infectious Disease Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology
Qixu Cai: Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology
Peiying Ho: Infectious Disease Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology
Yok Hian Chionh: Infectious Disease Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology
Meng Yuan: Institute of Quantitative Biology, Biochemistry and Biotechnology, University of Edinburgh
Abbas El Sahili: NTU Institute of Structural Biology, Nanyang Technological University
Linda A. Fothergill-Gilmore: Institute of Quantitative Biology, Biochemistry and Biotechnology, University of Edinburgh
Malcolm D. Walkinshaw: Institute of Quantitative Biology, Biochemistry and Biotechnology, University of Edinburgh
Julien Lescar: NTU Institute of Structural Biology, Nanyang Technological University
Peter C. Dedon: Infectious Disease Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology

DOI: https://doi.org/10.1038/s41467-017-02086-y
Journal volume & issue: Vol. 8, no. 1
pp. 1 – 14

Abstract

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Pyruvate kinase (PYK) controls glycolytic flux. Here, the authors combine biochemical, structural and computational modelling studies to characterize the allosteric mechanisms regulating Mycobacterium tuberculosis PYK activity and show that AMP and glucose-6-phosphate are synergistic allosteric activators of the enzyme.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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