Cytochrome bc1-aa3 Oxidase Supercomplex As Emerging and Potential Drug Target Against Tuberculosis

Sindhu, T and Debnath, P (2022) Cytochrome bc1-aa3 Oxidase Supercomplex As Emerging and Potential Drug Target Against Tuberculosis. In: Current Molecular Pharmacology, 15 (2). pp. 380-392.

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Abstract

The cytochrome bc1-aa3 supercomplex plays an essential role in the cellular respiratory system of Mycobacterium Tuberculosis. It transfers electrons from menaquinol to cytochrome aa3 (Complex IV) via cytochrome bc1 (Complex III), which reduces the oxygen. The electron transfer from a variety of donors into oxygen through the respiratory electron transport chain is essential to pump protons across the membrane creating an electrochemical transmembrane gradient (proton motive force, PMF) that regulates the synthesis of ATP via the oxidative phosphorylation process. Cytochrome bc1-aa3 supercomplex in M. tuberculosis is, therefore, a major drug target for antibiotic action. In recent years, several respiratory chain components have been targeted for developing new candidate drugs, illustrating the therapeutic potential of obstructing energy conversion of M. tuberculosis. The recently available cryo-EM structure of mycobacterial cytochrome bc1-aa3 super-complex with open and closed conformations has opened new avenues for understanding its structure and function for developing more effective, new therapeutics against pulmonary tuberculosis. In this review, we discuss the role and function of several components, subunits, and drug targeting elements of the supercomplex cytochrome bc1-aa3 and its potential inhibitors in detail. © 2022 Bentham Science Publishers.

Item Type:	Journal Article
Publication:	Current Molecular Pharmacology
Publisher:	Bentham Science Publishers
Additional Information:	The copyright for this article belongs to the Bentham Science Publishers.
Keywords:	cardiolipin; cytochrome aa3 complex; cytochrome bc1 aa3 oxidase supercomplex; imidazo1,2 apyridine derivative; imidazo2,1 bthiazole 3 carboxamide derivative; lansoprazole; lansoprazole sulfide; morpholino thiophene derivative; phenoxy alkyl benzimidazole derivative; pyrrolo3 4 cpyridine 1,3 dione; QcrA rieske iron sulfur protein; QcrB cytochrome b subunit; QcrC cytochrome bcsubunit; telacebec; tuberculostatic agent; ubiquinol cytochrome c reductase; unclassified drug; cytochrome c oxidase; oxidoreductase; oxygen; ubiquinol cytochrome c reductase, drug targeting; electron transport; human; Mycobacterium tuberculosis; nonhuman; oxidative phosphorylation; protein function; protein subunit; Review; tuberculosis; chemistry; drug delivery system; metabolism; Mycobacterium tuberculosis, Drug Delivery Systems; Electron Transport Complex III; Electron Transport Complex IV; Humans; Mycobacterium tuberculosis; Oxidoreductases; Oxygen; Tuberculosis
Department/Centre:	Division of Interdisciplinary Sciences > Computational and Data Sciences
Date Deposited:	03 Oct 2022 05:29
Last Modified:	06 Oct 2022 05:27
URI:	https://eprints.iisc.ac.in/id/eprint/76851

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