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Current Molecular Pharmacology

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ISSN (Print): 1874-4672
ISSN (Online): 1874-4702

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Review Article

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

Author(s): Thangaraj Sindhu and Pal Debnath*

Volume 15, Issue 2, 2022

Published on: 21 December, 2021

Article ID: e280921196875 Pages: 13

DOI: 10.2174/1874467214666210928152512

Price: $65

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 supercomplex 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.

Keywords: Mycobacterium tuberculosis, electron transport chain, oxidative phosphorylation, anti-TB agents, QcrB, bc1-aa3 oxidase supercomplex.

Graphical Abstract

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