Mycobacterial F1F0-ATP synthase

Mycobacterial F1F0-ATP synthase is a multi-subunit, membrane-embedded enzyme complex essential for the survival of mycobacteria such as Mycobacterium tuberculosis. It converts the transmembrane electrochemical proton gradient into ATP via a rotary mechanism. The complex consists of an F1 catalytic domain and a membrane-bound Fo domain containing the c-ring rotor, with mycobacteria-specific sequence features in the α, γ, and δ subunits that are attractive for species-selective drug targeting. Inhibition of this enzyme blocks ATP production, collapses cellular energy homeostasis, and is bactericidal, which has led to its clinical targeting by antibiotics like bedaquiline—a major advance in tuberculosis therapy. The enzyme's unique structural elements, critical for ATP hydrolysis and synthesis, make it an important target for new anti-mycobacterial agents, although issues like resistance and potential host toxicity must be managed.

Other names

Mycobacterial F-ATP synthaseMycobacterial F1Fo-ATP synthaseMycobacterial ATP synthase

Inhibition of proton-driven rotary catalysis by binding to the c-subunit (e.g., bedaquiline stabilizes and blocks the c-ring, halting ATP synthesis); Disruption of intracellular ATP levels, leading to bactericidal activity