Structure of mycobacterial CIII₂CIV₂ respiratory supercomplex bound to the tuberculosis drug candidate telacebec (Q203).

ABSTRACT: The imidazopyridine telacebec, also known as Q203, is one of only a few new classes of compounds in more than 50 years with demonstrated antituberculosis activity in humans. Telacebec inhibits the mycobacterial respiratory supercomplex composed of complexes III and IV (CIII₂CIV₂). In mycobacterial electron transport chains, CIII₂CIV₂ replaces canonical CIII and CIV, transferring electrons from the intermediate carrier menaquinol to the final acceptor, molecular oxygen, while simultaneously transferring protons across the inner membrane to power ATP synthesis. We show that telacebec inhibits the menaquinol:oxygen oxidoreductase activity of purified Mycobacterium smegmatis CIII₂CIV₂ at concentrations similar to those ne

SUBMITTER: Yanofsky DJ 

PROVIDER: S-EPMC8523172 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature