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

Escherichia coli F1Fo-ATP synthase is a complex, membrane-bound enzyme that plays a central role in energy transduction by coupling the flow of protons across the inner membrane to the synthesis of adenosine triphosphate (ATP) (UniProt Consortium, 2023). The enzyme is composed of two distinct sectors: the F1 catalytic domain, which extends into the cytoplasm, and the Fo proton-conducting domain, which is embedded within the phospholipid bilayer (Walker, 2013). In E. coli, the enzyme is reversible, allowing it to either produce ATP during oxidative phosphorylation or maintain a proton gradient through ATP hydrolysis during fermentation (Ahmad et al., 2020). Because of its vital role in maintaining cellular energy homeostasis and the proton motive force, it is a prominent target for antimicrobial research (Hong-Geller et al., 2020). While many clinical inhibitors like bedaquiline are specific to mycobacteria, the E. coli enzyme serves as the primary structural and functional model for understanding bacterial F-type ATPases. Therapeutic strategies targeting this enzyme aim to disrupt bacterial viability by depleting energy reserves or collapsing the electrochemical gradient. However, a major challenge in drug development is ensuring selectivity to avoid inhibiting the highly conserved human mitochondrial ATP synthase (PubMed, 2021).

Other names

F-type ATPaseF1Fo-ATPaseH(+)-transporting two-sector ATPaseATP phosphohydrolaseBacterial ATP synthase

Inhibition of the rotary catalysis mechanism by either blocking the Fo proton channel or binding to the F1 catalytic subunits, thereby preventing the coupling of proton translocation to ATP synthesis/hydrolysis.