ATP synthase enzyme of Mycobacterium tuberculosis (F₁F₀-ATP synthase (sometimes abbreviated as Mtb ATP synthase or F-ATP synthase in literature))

The ATP synthase enzyme of Mycobacterium tuberculosis is an essential, multi-subunit enzyme complex that generates cellular ATP from ADP and inorganic phosphate by utilizing the proton motive force across the bacterial membrane. Its structure comprises distinct α, β, γ, δ, ε, a, b, b′, and c subunits, with unique features not shared by human mitochondrial ATP synthase. The mycobacterial enzyme is required for both actively replicating and dormant states, making it indispensable for bacterial viability and an attractive target for anti-tubercular therapy. Bedaquiline, a diarylquinoline, specifically inhibits the c-ring of mycobacterial ATP synthase and is used to treat multidrug-resistant TB, but resistance and toxicity remain clinical challenges. Structural studies have revealed mycobacterium-specific subunit features (such as the γ-loop and αCTD) that may allow development of further species-selective inhibitors to address resistance and safety concerns.

Other names

Mycobacterial F₁F₀-ATP synthaseMycobacterium tuberculosis ATP synthaseF-ATP synthase (Mtb)Mtb ATP synthase

Inhibition of ATP synthesis by binding to the c-ring (rotor), preventing proton translocation and enzyme rotation. Targeting unique mycobacterial structural elements (e.g., γ-subunit loop, αCTD), resulting in species-selective inhibition. Prevention of energy production leads to depletion of ATP and rapid mycobacterial death.