ATP synthase subunit c (AtpE) (AtpE)

The Mycobacterium tuberculosis F-ATP synthase c-ring subunit, commonly known as AtpE, is an essential component of the bacterial F1Fo-ATP synthase complex responsible for generating adenosine triphosphate (ATP) through oxidative phosphorylation [1, 2]. This subunit forms a membrane-embedded rotary ring that facilitates the translocation of protons across the cytoplasmic membrane, a process that drives the mechanical rotation of the enzyme's central stalk to catalyze ATP synthesis [6, 8]. It is the primary therapeutic target of the diarylquinoline drug bedaquiline, which binds to a specific site at the interface of the c-subunits, effectively stalling the rotary mechanism and depleting the bacterium's energy reserves [1, 4]. The high selectivity of drugs for the mycobacterial c-ring over the human mitochondrial counterpart makes it a critical target for treating multidrug-resistant and extensively drug-resistant tuberculosis [2, 9]. Resistance to bedaquiline often arises from specific missense mutations within the atpE gene, which alter the drug-binding pocket [11, 14]. Despite its efficacy, targeting this subunit with bedaquiline is associated with clinical challenges, most notably the risk of QT interval prolongation and cardiotoxicity [4, 15].

Other names

Mycobacterium tuberculosis F-ATP synthase c-ring subunitSubunit cF-type H+-transporting ATP synthase subunit cc-subunitAtpE proteinF-ATP synthase c-ring

Inhibition of ATP synthase by binding to the c-ring subunit, stalling rotation and blocking proton translocation, which leads to ATP depletion.