Mycobacterium tuberculosis ATP synthase subunit c (AtpE)

The Mycobacterium tuberculosis ATP synthase subunit c, encoded by the atpE gene, is a vital component of the F0 sector of the F1F0 ATP synthase complex. This transmembrane protein forms a rotating oligomeric ring (c-ring) that facilitates proton translocation across the bacterial plasma membrane, driving the synthesis of adenosine triphosphate (ATP) (UniProt P9WPU1). As M. tuberculosis is an obligate aerobe that depends on oxidative phosphorylation for energy production, the ATP synthase complex is essential for its survival in both replicating and non-replicating states (PubMed: 15647434). The subunit c is the primary target of the diarylquinoline class of antibiotics, most notably Bedaquiline, which binds to specific residues within the c-ring to block the proton pump mechanism (PubMed: 24434183). This inhibition leads to a rapid depletion of intracellular ATP levels and subsequent bactericidal activity against multi-drug resistant strains of tuberculosis (PubMed: 25157111). Clinical resistance to Bedaquiline is frequently associated with mutations in the atpE gene, confirming the subunit's role as the drug's molecular target (PubMed: 30135115).

Other names

ATP synthase C chainF-type H+-transporting ATPase subunit cSubunit cAtpE

Inhibition of the F0 subunit of ATP synthase, preventing proton translocation and ATP production.