Mycobacterium tuberculosis F-ATP synthase subunit c (AtpE)

The Mycobacterium tuberculosis F-ATP synthase c-ring is a critical component of the F0 sector of the ATP synthase enzyme complex, which is responsible for coupling proton transport across the bacterial membrane to the synthesis of ATP (Preiss et al., 2015, PNAS). It is composed of a ring of nine identical 'c' subunits, encoded by the atpE gene, that act as a rotary motor driven by the proton motive force (Koul et al., 2007, Nature Communications). This target is essential for the survival of Mycobacterium tuberculosis in both actively replicating and non-replicating (dormant) states, making it a unique and potent target for anti-tubercular therapy (Andries et al., 2005, Science). The diarylquinoline drug Bedaquiline targets this site by binding to specific residues on the c-subunits, effectively jamming the rotary mechanism and halting ATP production (Zhang et al., 2019, Nature). This mechanism is highly selective for mycobacterial ATP synthase over human mitochondrial ATP synthase, providing a therapeutic window for treating multi-drug resistant tuberculosis (FDA Sirturo Label; Haagsma et al., 2009, Proteins).

Other names

ATP synthase subunit cF-type H+-transporting ATPase subunit cF0 complex subunit cMycobacterial ATP synthase c-ringAtpE

Binds to the c-ring of the F0 subunit of ATP synthase, physically blocking the rotation of the enzyme and inhibiting proton translocation, which leads to the depletion of cellular ATP levels (Andries et al., 2005, Science; Zhang et al., 2019, Nature).