Structural snapshots of Mycobacterium tuberculosis enolase reveal dual mode of 2PG binding and its implication in enzyme catalysis.

Mycobacterium tuberculosis X-ray crystallography cryo-electron microscopy enolase enzyme mechanisms gluconeogenesis

Journal

IUCrJ
ISSN: 2052-2525
Titre abrégé: IUCrJ
Pays: England
ID NLM: 101623101

Informations de publication

Date de publication:
01 Nov 2023
Historique:
received: 16 05 2023
accepted: 27 09 2023
medline: 2 11 2023
pubmed: 20 10 2023
entrez: 20 10 2023
Statut: epublish

Résumé

Enolase, a ubiquitous enzyme, catalyzes the reversible conversion of 2-phosphoglycerate (2PG) to phosphoenolpyruvate (PEP) in the glycolytic pathway of organisms of all three domains of life. The underlying mechanism of the 2PG to PEP conversion has been studied in great detail in previous work, however that of the reverse reaction remains to be explored. Here we present structural snapshots of Mycobacterium tuberculosis (Mtb) enolase in apo, PEP-bound and two 2PG-bound forms as it catalyzes the conversion of PEP to 2PG. The two 2PG-bound complex structures differed in the conformation of the bound product (2PG) viz the widely reported canonical conformation and a novel binding pose, which we refer to here as the alternate conformation. Notably, we observed two major differences compared with the forward reaction: the presence of Mg

Identifiants

pubmed: 37860976
pii: S2052252523008485
doi: 10.1107/S2052252523008485
pmc: PMC10619443
doi:

Substances chimiques

Phosphopyruvate Hydratase EC 4.2.1.11

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

738-753

Informations de copyright

open access.

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Auteurs

Mohammed Ahmad (M)

Structural and Functional Biology Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.

Bhavya Jha (B)

Structural and Functional Biology Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.

Sucharita Bose (S)

Institute for Stem Cell Science and Regenerative Medicine, Bangalore 560065, India.

Satish Tiwari (S)

Structural and Functional Biology Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.

Abhisek Dwivedy (A)

Structural and Functional Biology Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.

Deepshikha Kar (D)

Structural and Functional Biology Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.

Ravikant Pal (R)

Structural and Functional Biology Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.

Richard Mariadasse (R)

Department of Bioinformatics, Alagappa University, Karaikudi, Tamil Nadu 630003, India.

Tanya Parish (T)

Infectious Disease Research Institute, 1616 Eastlake Avenue E, Suite 400, Seattle, WA 98102, USA.

Jeyaraman Jeyakanthan (J)

Department of Bioinformatics, Alagappa University, Karaikudi, Tamil Nadu 630003, India.

Kutti R Vinothkumar (KR)

National Centre for Biological Sciences, Tata Institute for Fundamental Research, Bangalore 560065, India.

Bichitra Kumar Biswal (BK)

Structural and Functional Biology Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.

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