Bacterial ATP synthase (F1Fo-ATP synthase) pathway (F1Fo-ATP synthase pathway (also written F1F0-ATP synthase pathway))

The bacterial ATP synthase pathway refers to the F1Fo-ATP synthase–driven process that converts a transmembrane proton motive force into chemical energy by synthesizing ATP from ADP and inorganic phosphate. The enzyme comprises a soluble F1 catalytic head (α3β3γδε) and a membrane-embedded Fo motor (a, b2, c-ring) linked by central and peripheral stalks; rotation of the c-ring and γ/ε subunits driven by proton flow through two offset half-channels in subunit a powers conformational changes at the three catalytic β sites to form ATP. High-resolution bacterial structures define the ion half-channels, the rotor–stator interface, and conserved residues (e.g., c-ring glutamate and a-subunit arginine) that mediate reversible ion binding and exchange during torque generation. Clinically, ATP synthase is a validated antibacterial target: bedaquiline binds the c-ring of the mycobacterial enzyme to block ATP production and kill Mycobacterium tuberculosis, and diverse natural and synthetic inhibitors (e.g., venturicidin, oligomycin, tomatidine, quinolines) target the c-ring or F1 interfaces across bacteria, though achieving potency and selectivity, and overcoming efflux in Gram-negatives, remain key challenges.

Other names

ATP synthase pathwayBacterial F-type ATP synthase pathwayF-type ATPase pathwayProton motive force–driven ATP synthesis pathway

Inhibition of proton-coupled rotation by binding to c-ring near H+ binding sites, blocking energy transduction (e.g., bedaquiline, oligomycin, venturicidin). Stabilization or disruption of regulatory “hook-and-catch” inhibitory features in mycobacterial enzyme to prevent ATP synthesis. Interference with F1 catalytic sector interactions at α/β/γ interface, impairing catalysis (e.g., resveratrol, piceatannol). Covalent or tight-binding modification of c subunit carboxylates (e.g., DCCD) to block ion binding/translocation.