Mycobacterium tuberculosis F-ATP synthase epsilon subunit (atpC) (atpC)

The Mycobacterium tuberculosis F-ATP synthase epsilon subunit, encoded by the atpC gene, is an essential regulatory component of the bacterial F1FO-ATP synthase complex [1, 3]. It serves as a critical coupling factor that links the rotation of the membrane-embedded c-ring to the catalytic alpha3beta3 headpiece, thereby driving the synthesis of ATP [2, 5]. A unique feature of the mycobacterial epsilon subunit is its role as an intrinsic inhibitor of ATP hydrolysis, which prevents the bacterium from wasting energy during dormant or hypoxic states when the proton motive force is low [4, 6]. This regulatory function is vital for the survival and persistence of M. tuberculosis within the host environment [3, 5]. The epsilon subunit has been identified as a target for the anti-tubercular drug Bedaquiline (TMC207), which binds to a site involving both the c-ring and the epsilon subunit, acting as a molecular wedge to halt enzyme rotation [2, 5]. Additionally, novel experimental inhibitors such as EpNMF1 have been developed to specifically target the N-terminal domain of the epsilon subunit, offering a potential strategy to overcome drug resistance [1]. Because the mycobacterial epsilon subunit possesses structural characteristics distinct from its human mitochondrial counterpart, it represents a promising target for the development of highly selective and potent anti-mycobacterial therapies [3, 6]. References: [1] PMC9104444; [2] PMC3195019; [3] Gosset, 2024; [4] PMC3195019; [5] ResearchGate/PDB 5YIO; [6] Springer Nature, 2024.

Other names

ATP synthase subunit epsilonatpCF1 sector epsilon subunitMtεF-type ATPase subunit epsilon

Inhibition of ATP synthesis by binding to the epsilon subunit and/or the c-ring interface, preventing the rotation of the enzyme complex and depleting cellular energy stores [1, 2, 4].