Mycobacterium tuberculosis ATP synthase (Mtb ATP synthase) (Mtb ATP synthase)

Mycobacterium tuberculosis ATP synthase is a membrane-bound enzyme complex essential for the energy metabolism of the tubercle bacillus, functioning as the primary source of cellular energy [UniProt]. It operates as a rotary motor that couples the flow of protons down an electrochemical gradient to the synthesis of adenosine triphosphate (ATP) from ADP and inorganic phosphate [PubMed, PMID: 25053707]. The enzyme consists of two main sectors: the F1 catalytic domain and the F0 proton-translocating domain [PubMed, PMID: 25053707]. Unlike many other pathogens, M. tuberculosis is an obligate aerobe that relies heavily on oxidative phosphorylation for survival, even during latent or non-replicating phases [Nature, PMID: 15650724]. This reliance makes the ATP synthase a critical target for therapeutic intervention in tuberculosis treatment. The drug Bedaquiline (Sirturo) specifically targets the c-subunit of the F0 domain, inhibiting the rotation of the enzyme and leading to a lethal depletion of cellular ATP [Science, PMID: 24723610]. This mechanism is particularly effective against multi-drug-resistant (MDR) and extensively drug-resistant (XDR) strains of tuberculosis. The target is highly validated due to its high selectivity for the bacterial enzyme over human mitochondrial ATP synthase, which reduces the risk of host toxicity [JBC, PMID: 22334655]. Emerging drugs like TBAJ-587 and TBAJ-876 are also being developed to target this complex with improved safety profiles.

Other names

F1F0-ATP synthaseATP phosphohydrolaseH+-transporting ATP synthaseATP synthase subunit catpE

Inhibition of the c-subunit of the F0 domain, preventing rotary catalysis and ATP production.