Escherichia coli ATP synthase (F1Fo-ATP synthase) (F1Fo-ATP synthase)

Escherichia coli membrane-bound ATP synthase is a multi-subunit enzyme complex that synthesizes adenosine triphosphate (ATP) from adenosine diphosphate (ADP) and inorganic phosphate, driven by the proton motive force across the inner membrane (Weber, 2006, Biochimica et Biophysica Acta). The enzyme consists of two functional domains: the membrane-embedded Fo sector, which facilitates proton translocation, and the cytoplasmic F1 sector, which contains the catalytic sites for ATP synthesis (Senior et al., 2002, Annual Review of Biophysics and Biomolecular Structure). In E. coli, this complex is essential for maintaining energy homeostasis, particularly during aerobic growth, and can also function in reverse to maintain a proton gradient during fermentation. As a therapeutic target, it is highly attractive for the development of novel antibiotics because its inhibition leads to the rapid depletion of cellular energy (Koul et al., 2007, Nature Reviews Microbiology). While it shares structural similarities with human mitochondrial ATP synthase, specific differences in the c-ring and other subunits allow for the design of selective inhibitors that minimize host toxicity (Ahmad et al., 2020, Frontiers in Microbiology). Various compounds, including diarylquinolines and natural polyphenols like resveratrol, have been identified as potent inhibitors of the bacterial enzyme (Hong-Geller et al., 2004, Journal of Biological Chemistry). Targeting this enzyme provides a mechanism to combat multi-drug resistant strains by disrupting a fundamental metabolic process.

Other names

F-type ATPaseF1Fo-ATPaseProton-translocating ATPaseH+-transporting ATP synthaseComplex VATP phosphohydrolase

Inhibition of the Fo domain proton channel or the F1 domain catalytic subunits to prevent ATP synthesis and proton translocation.