Bacterial H+-transporting ATP synthase (F-ATPase)

The bacterial H+-transporting ATP synthase, also known as F-type ATPase or F1Fo-ATPase, is a multi-subunit enzyme complex essential for energy production in bacteria [1, 5]. It functions as a rotary motor that couples the flow of protons across the cytoplasmic membrane to the synthesis of ATP from ADP and inorganic phosphate [5, 13]. The enzyme consists of two main sectors: the membrane-embedded Fo sector, which facilitates proton translocation, and the cytoplasmic F1 sector, which catalyzes the chemical reaction [5, 13]. In addition to ATP synthesis, the enzyme can operate in reverse, hydrolyzing ATP to pump protons and maintain pH homeostasis, which is critical for bacterial survival under acidic stress [6, 22]. This target is clinically validated by the drug bedaquiline, a diarylquinoline antibiotic used to treat multidrug-resistant tuberculosis [1, 2]. Bedaquiline selectively inhibits the mycobacterial version of the enzyme by binding to the c-ring and epsilon subunits, stalling the motor and leading to a lethal depletion of cellular ATP [3, 5]. Therapeutic use of bedaquiline is associated with safety concerns such as QTc interval prolongation and hepatotoxicity, necessitating careful patient monitoring [1, 2].

Other names

F1Fo-ATPaseATP synthaseProton-pumping ATPaseF-type ATPaseMycobacterial ATP synthaseH+-transporting ATPase

Inhibition of the rotary motor mechanism by binding to the c-subunit and epsilon subunit, preventing proton-coupled ATP synthesis and leading to ATP depletion.