ATP synthase from Mycobacterium tuberculosis (F₁F₀-ATP synthase (sometimes abbreviated as ATP synthase; more specifically, "F₁F₀-ATP synthase" is used in literature to denote the enzyme complex[8][9]))

ATP synthase from Mycobacterium tuberculosis is a large multi-subunit enzyme complex, essential for bacterial energy production by converting the proton-motive force across the membrane into adenosine triphosphate (ATP) via rotary catalysis[8]. It is composed of F₁ (soluble catalytic) and F₀ (membrane-embedded proton channel) components, with unique structural elements in mycobacteria—including extended alpha subunit C-termini, mycobacterial-specific loops in γ and ε subunits, and unique peripheral stalk interactions—that distinguish it from mitochondrial homologs and are exploited for drug design[1][6][8][9]. The enzyme is required for growth and survival both in active (aerobic) and latent (hypoxic) states of M. tuberculosis, making it a validated therapeutic target, as evidenced by the clinical use of the ATP synthase inhibitor bedaquiline, which binds to the c-ring and blocks its rotary mechanism, depleting cellular ATP and leading to cell death[3][5][8][10]. Novel inhibitors under investigation exploit the distinctive mycobacterial architecture to achieve selectivity and overcome current drug resistance, though mitochondrial toxicity is a key safety concern for clinical translation[5][9].

Other names

F₁F₀-ATP synthaseF-ATPaseATP synthase complexMycobacterial ATP synthase

Inhibition of proton translocation and ATP synthesis by binding to the c-ring (rotor) of ATP synthase, stalling enzyme rotation and energy production (as seen with BDQ)[10] Allosteric inhibition at unique mycobacterial structural features, e.g. "hook and catch" and "fail-safe" domains[1][9] Targeting subunit-specific sites (a, c, ε, γ, δ subunits)[5][6] RNA-guided knockdown (research tools)[7]