Bacterial F1Fo-ATPase (F1Fo-ATPase)

The bacterial membrane H+-ATPase, primarily the F1Fo-ATPase (also known as ATP synthase), is a vital multi-subunit enzyme complex located in the cytoplasmic membrane of bacteria. It plays a dual role in cellular energetics: it can synthesize ATP using the energy of a transmembrane proton gradient (proton motive force) or hydrolyze ATP to pump protons out of the cell to maintain pH homeostasis and membrane potential [2, 5]. This enzyme is particularly crucial for the survival of Mycobacterium tuberculosis, including its dormant and drug-resistant forms, making it a validated target for anti-tuberculosis therapy [7, 11]. The drug bedaquiline selectively inhibits the mycobacterial F1Fo-ATPase by binding to the c-subunit of the Fo rotor, thereby halting ATP production and leading to bacterial death [7, 11]. Due to significant structural differences between bacterial and human mitochondrial ATP synthases, this target offers a high degree of selective toxicity, although monitoring for potential side effects like QT prolongation remains necessary in clinical practice [11].

Other names

Bacterial membrane H+-ATPaseBacterial ATP synthaseProton-translocating ATPaseF-type ATPaseH+-transporting ATP synthaseBF1Fo

Inhibition of the proton-pumping and ATP-synthesis activity by binding to the c-subunit of the Fo rotor or the F1 catalytic domain, leading to ATP depletion and dissipation of the proton motive force.