Mycobacterial F1Fo-ATP synthase (F1Fo-ATP synthase)

The mycobacterial F1Fo-ATP synthase is a large, membrane-embedded enzyme complex essential for ATP production in Mycobacterium species, including Mycobacterium tuberculosis[1][5][3]. It is composed of a soluble F1 sector (subunits α3:β3:γ:δ:ε) responsible for ATP synthesis and a membrane-embedded Fo sector (subunits a:b:b':c9) that forms a rotary motor powered by the proton-motive force[2][4][7]. Unique structural adaptations in mycobacteria include an extended δ subunit and mycobacterium-specific features of the γ and α subunits, which are involved in regulation and species-selective inhibition[3][5]. The enzyme is indispensable for both actively replicating and dormant mycobacteria, making it an attractive therapeutic target[3]. Bedaquiline and related drugs specifically bind the c-ring of the Fo rotor, blocking proton translocation and ATP synthesis, which leads to bacterial death but is generally selective for the mycobacterial enzyme due to differences in binding site structure[1][8]. The essential function and unique mycobacterial elements provide opportunities for selective drug discovery against tuberculosis and related infections[3][5].

Other names

F-ATP synthaseMycobacterial ATP synthaseATP synthaseFoF1-ATPase

Direct inhibition of proton translocation and ATP synthesis by binding to the c-ring of the Fo rotor, preventing rotation and ion flow, thus collapsing ATP generation and leading to mycobacterial death[1][3][8].