Mycobacterial F1Fo ATP synthase epsilon subunit (atpC)

The Mycobacterial F1Fo ATP synthase epsilon subunit, encoded by the atpC gene, is a critical regulatory component of the mycobacterial energy machinery [UniProt: P9WPU1]. It functions as an endogenous inhibitor of ATP hydrolysis, ensuring that the bacterium does not deplete its ATP stores under conditions where the proton motive force is insufficient for synthesis [PubMed: 25108336]. This subunit is particularly notable in Mycobacterium tuberculosis for its unique C-terminal domain, which undergoes significant conformational changes to regulate the enzyme's activity [PubMed: 32434915]. Because the mycobacterial epsilon subunit possesses structural features distinct from its human mitochondrial counterpart, it represents a highly attractive target for the development of narrow-spectrum antitubercular agents [PubMed: 29158454]. Targeting this subunit can disrupt the energy homeostasis of both actively growing and dormant mycobacteria, offering a potential pathway to treat multi-drug resistant tuberculosis [PubMed: 30355740]. While the approved drug Bedaquiline targets the Fo c-ring of the same enzyme complex, the epsilon subunit is the focus of ongoing research into new classes of inhibitors that stabilize its inhibitory state [PubMed: 32434915].

Other names

ATP synthase subunit epsilonatpCF-type ATPase epsilon subunitF1 sector epsilon subunit

Inhibition of ATP synthesis and hydrolysis by stabilizing the inhibitory C-terminal domain of the epsilon subunit, thereby blocking the rotation of the gamma-epsilon central stalk relative to the alpha3beta3 hexamer [PubMed: 25108336, PubMed: 32434915].