Mycobacterial F1FO-ATP synthase subunit c (atpE)

The Mycobacterial F1FO-ATP synthase subunit c, commonly known as the c-ring, is a critical component of the energy-producing machinery in mycobacteria, including Mycobacterium tuberculosis (Andries et al., 2005, Science). It forms a transmembrane ring structure within the FO sector of the ATP synthase enzyme, functioning as a rotary motor driven by the proton motive force (Preiss et al., 2015, PNAS). As protons move through the interface between the c-ring and the 'a' subunit, the ring rotates, providing the mechanical energy required for the F1 sector to synthesize ATP from ADP and inorganic phosphate (Koul et al., 2007, Nature). This process is essential for the survival of both actively replicating and dormant mycobacteria, making it a highly effective therapeutic target (UniProt P9WPU1). The diarylquinoline drug Bedaquiline targets this subunit by binding to a specific pocket, which physically blocks the rotation of the c-ring and halts ATP production (Preiss et al., 2015, PNAS). This inhibition results in a rapid depletion of cellular energy and eventual bacterial death, providing a breakthrough treatment for multi-drug-resistant tuberculosis (Mahajan, 2013, International Journal of Applied and Basic Medical Research).

Other names

ATP synthase subunit cF-type H+-transporting ATPase subunit cF0 complex subunit cMycobacterial ATP synthase c-ringATP synthase C chain

Bedaquiline and its derivatives bind to the c-ring of the F0 subunit of the mycobacterial ATP synthase, specifically interacting with the ion-binding site (e.g., Glu61 in M. tuberculosis). This binding physically obstructs the rotation of the c-ring, which is essential for proton translocation across the membrane, thereby inhibiting the synthesis of ATP and leading to bacterial cell death (Andries et al., 2005, Science; Preiss et al., 2015, PNAS).