Structural insights of mycobacterial ATP synthase and recent updates on molecular recognition of Mtb ATP synthase inhibitors: a review.

In mycobacteria, the F1Fo-ATP synthase enzyme comprises five polypeptide chains (Chain α, β, γ, ε, δ) and three subunits (Subunit a, b, and c), respectively. ATP is fundamental for the survival and growth of mycobacterial strains. In tuberculosis, this enzyme survives in harsh conditions like hypoxia, fluctuations in pH, and low nutrition in the host, further coercing it to enter the dormant state. Depletion of ATP stopgap the mycobacterial strains strenuous to survive. The discovery of Bedaquiline in 2012 has validated mycobacterial ATP synthase as a substantial target to combat resistance developed in mycobacterial strains. Recent research work done against mycobacterial ATP synthase provides a platform for a better understanding of structural features of chemical compounds and targeting unique epitopes of the ATP synthase enzyme in designing novel therapeutics against tuberculosis. This article summarizes the structural organizations as well as the solitary epitopes present in mycobacterial F1Fo-ATP synthase. It also highlights its distinguished features from similar enzymes present in eukaryotes, fungi, and other bacterial species. Additionally, the present work reviews recent updates on various heterocyclic active chemical compounds designed as mycobacterial ATP synthase inhibitors for the treatment of tuberculosis till 2025.