Bacterial proton-translocating F-type ATPase (F-ATPase)

The bacterial proton-translocating F-type ATPase, also known as F1Fo-ATP synthase, is a fundamental enzyme complex responsible for the synthesis of adenosine triphosphate (ATP) in bacteria [1]. It operates as a rotary motor, utilizing the electrochemical gradient of protons (the proton motive force) across the plasma membrane to drive the phosphorylation of ADP [2]. The enzyme is composed of two distinct sectors: the membrane-bound Fo sector, which acts as a proton channel, and the peripheral F1 sector, which contains the catalytic sites for ATP synthesis [3]. This target is particularly significant in the treatment of multi-drug-resistant tuberculosis, where the drug bedaquiline binds to the c-subunit of the Fo rotor, halting the rotation and depleting the bacterium's energy supply [4]. Because of structural divergence between bacterial and eukaryotic mitochondrial ATP synthases, this enzyme serves as a highly selective target for antimicrobial therapy [5].

Other names

F1Fo-ATP synthaseBacterial ATP synthaseH+-transporting ATP synthaseF-type ATPaseComplex V

Inhibition of the rotary mechanism of the F-type ATPase, specifically by binding to the c-subunit of the Fo domain, which prevents proton translocation and subsequent ATP synthesis [4].