Structural insights of <i>mycobacterial</i> ATP synthase and recent updates on molecular recognition of <i>Mtb</i> ATP synthase inhibitors: a review

In <i>mycobacteria</i>, the F₁Fo-ATP synthase enzyme comprises five polypeptide chains (Chain <b>α, β, γ, ε, δ)</b> and three subunits (Subunit <b>a</b>, <b>b</b>, and <b>c</b>), respectively. ATP is fundamental for the survival and growth of <i>mycobacterial strains</i>. 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 <i>mycobacterial</i> strains strenuous to survive. The discovery of Bedaquiline in 2012 has validated <i>mycobacterial</i> ATP synthase as a substantial target to combat resistance developed in <i>mycobacterial</i> strains. Recent research work done against <i>mycobacterial</i> 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 <i>mycobacterial</i> <b>F</b>_<b>1</b><b>Fo</b>-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 <i>mycobacterial</i> ATP synthase inhibitors for the treatment of tuberculosis till 2025.