Mycobacterial cytochrome bc1 complex (bc1 complex) (bc1 complex)

The mycobacterial cytochrome bc1 complex is an essential enzyme assembly within the respiratory chain of Mycobacterium tuberculosis, often functioning as part of a larger bc1-aa3 supercomplex [Source: Nature Communications, 2021, PMID: 34145254]. It plays a critical role in energy metabolism by transferring electrons from menaquinol to the terminal oxidase, a process coupled to the generation of the proton motive force required for ATP synthesis [Source: UniProt, P9WNJ1]. Unlike many other bacteria, M. tuberculosis relies heavily on this oxidative phosphorylation pathway for survival during both aerobic growth and latent persistence, making it a high-value therapeutic target [Source: Journal of Biological Chemistry, 2018, PMID: 29921588]. Several novel anti-tuberculosis drug candidates, most notably the imidazopyridine Telacebec (Q203), specifically target the QcrB subunit of this complex [Source: NEJM, 2019, PMID: 31644843]. By binding to the ubiquinol-binding site, these inhibitors effectively shut down the bacterial "power plant," leading to potent bactericidal activity against drug-resistant strains while maintaining high selectivity over human mitochondrial complexes [Source: Nature Medicine, 2013, PMID: 23913123].

Other names

Cytochrome bc1-aa3 supercomplexUbiquinol-cytochrome c reductaseComplex IIIQcrBMenaquinol-cytochrome c reductase

Inhibition of the QcrB subunit (ubiquinol-binding site) of the cytochrome bc1 complex, which halts the electron transport chain and prevents ATP production [Source: Nature Medicine, 2013, PMID: 23913123].