Mycobacterial ATP synthase c subunit (AtpE)

The mycobacterial ATP synthase c subunit (AtpE) is a membrane-embedded component of the ATP synthase enzyme complex, essential for the synthesis of ATP by oxidative phosphorylation in mycobacteria such as Mycobacterium tuberculosis. The c subunit forms an oligomeric ring (typically composed of nine c-subunits in mycobacteria) that acts as a proton-translocating rotor; as protons move through the ring, this drives the rotational catalysis needed for ATP generation[1][3][9]. The c subunit is the direct molecular target of diarylquinoline antimycobacterial drugs like bedaquiline, which bind to the c-ring and block proton translocation, leading to inhibition of ATP synthesis and mycobacterial cell death[5][8]. This therapeutic targeting represents a novel and critical approach in tuberculosis pharmacotherapy, particularly for drug-resistant forms of the disease. Resistance can arise via mutations in atpE, the gene encoding the c subunit[8]. Human ATP synthase is significantly less sensitive to these inhibitors, supporting the therapeutic specificity of targeting mycobacterial AtpE[5].

Other names

ATP synthase subunit cAtpE

Inhibition of proton translocation through the c-ring; Stalling of ATP synthesis through binding and blocking ion-conducting sites; Uncoupling of the proton-motive force in mycobacterial membranes