Cytochrome b subunit of the cytochrome bc1 complex (QcrB) (QcrB)

The Cytochrome b subunit of the cytochrome bc1 complex (QcrB) is a vital component of the respiratory electron transport chain in Mycobacterium tuberculosis (UniProt: P9WNJ5). It functions as a transmembrane protein that facilitates the transfer of electrons from ubiquinol to cytochrome c1, a process coupled with proton translocation across the cytoplasmic membrane to generate a proton motive force (PubMed: 23913081). This electrochemical gradient is essential for ATP synthesis via ATP synthase, providing the energy required for bacterial growth and survival (PubMed: 30670640). In the context of disease, QcrB is a validated therapeutic target for treating multidrug-resistant and extensively drug-resistant tuberculosis (Nature Medicine, 2013). Small molecules such as Telacebec (Q203) and TB47 bind to the Qp site of the QcrB subunit, effectively halting cellular respiration and leading to bacterial death (PubMed: 30670640). However, the clinical utility of QcrB inhibitors can be challenged by the emergence of spontaneous mutations in the qcrB gene and the presence of alternative respiratory pathways, such as the cytochrome bd oxidase, which can partially bypass the bc1 complex (PubMed: 33432151).

Other names

Cytochrome bUbiquinol-cytochrome c reductase subunit bComplex III subunit bMTCY27G12.23

Inhibition of the ubiquinol-binding (Qp) site of the cytochrome bc1 complex, blocking electron transfer and ATP production.