Mycobacterium tuberculosis ATP synthase subunit c (AtpE) (AtpE)

The Mycobacterium tuberculosis ATP synthase c-ring is a key component of the F1F0-ATP synthase complex, an essential enzyme that synthesizes adenosine triphosphate (ATP) using a proton motive force across the plasma membrane (Andries et al., 2005). The c-ring is composed of nine identical AtpE subunits that form a rotor within the F0 sector of the enzyme (Preiss et al., 2015). As protons move through the complex, the c-ring rotates, driving the conformational changes in the F1 sector required for ATP production. This target is particularly significant because M. tuberculosis depends on ATP synthase for survival in both replicating and non-replicating states. The drug Bedaquiline (Sirturo) targets this structure by binding to specific residues on the AtpE subunits, physically blocking the rotation of the c-ring and halting ATP synthesis (Koul et al., 2007). This mechanism of action is highly selective for mycobacteria over human mitochondrial ATP synthase, providing a potent therapeutic window for treating multi-drug-resistant tuberculosis (MDR-TB).

Other names

ATP synthase F0 subunit cSubunit c of F1F0-ATP synthaseAtpE subunitMycobacterium tuberculosis ATP synthase c-ring

Bedaquiline binds to the c-ring of the F0 subunit of ATP synthase, physically blocking the rotation of the c-ring and inhibiting the proton pump mechanism, which leads to the depletion of cellular ATP levels and bacterial death (Andries et al., 2005; Science, 2020).