Cytochrome b subunit of the Mycobacterium tuberculosis cytochrome bc1-aa3 complex (QcrB)

The QcrB subunit is a critical component of the cytochrome bc1-aa3 supercomplex in Mycobacterium tuberculosis, serving as the primary site for ubiquinol oxidation within the bacterial respiratory chain. This enzyme complex is essential for maintaining the proton motive force required for ATP synthesis, which is vital for the survival and growth of the pathogen, including its dormant states. As a validated therapeutic target, QcrB is the site of action for several novel anti-tuberculosis drug candidates, most notably Telacebec (Q203). These inhibitors bind to the QcrB subunit, effectively halting cellular respiration and leading to rapid ATP depletion and bacterial death. Because the mycobacterial respiratory chain differs significantly from the human mitochondrial electron transport chain, QcrB offers a high degree of selectivity and a reduced risk of host toxicity. However, the emergence of resistance through specific point mutations in the qcrB gene remains a significant challenge in clinical development.

Other names

Ubiquinol-cytochrome c reductase cytochrome b subunitCytochrome bQcrB subunitMtb QcrB

Inhibition of the cytochrome bc1-aa3 oxidase complex by binding to the QcrB subunit, which blocks the electron transport chain, prevents the generation of a proton motive force, and leads to the depletion of intracellular ATP in Mycobacterium tuberculosis.