Bacterial FOF1 ATP: Nanomotor for ATP Synthesis and Hydrolysis and Mechanism of Interaction with the Macrolide Antibiotic Oligomycin A

Abstract FOF1-ATP synthase is a highly conserved enzyme of eukaryotic or bacterial cells. This enzyme contains eight species of various subunits in bacteria. The F1 sector contains subunits α3, β3, γ, δ, and ε, and the FO sector contains subunits a, b2, and c(10–15). According to modern nomenclature, the rotor of FOF1-ATF synthase consists of the γ, ε, and c subunits; the stator of the enzyme molecule includes the α3, β3, δ, a, and b2 subunits. The rotation of the complex relative to the stator subunits leads to the synthesis or hydrolysis of ATP with the translocation of protons through the a subunit and c ring of the FO sector. The most famous ATP synthase inhibitor is oligomycin A. Oligomycin A inhibits proton translocation in the FOF1-ATP synthase complexes, which leads to an impaired energy metabolism in cells. Oligomycin has a cytotoxic effect against a number of pathogenic bacteria and a high antitumor activity due to the inactivation of FOF1-ATF synthase, a promising biological target for modern drugs. Since FOF1-ATP synthase is highly conserved and ATP synthesis is one of the central processes necessary for the vital functions of cells, this enzyme is a promising biotarget for new antibacterial drugs synthesized based on oligomycin A. This article describes the latest data on the functioning of ATP synthase in bacterial and eukaryotic cells, as well as recent work on the development of new antibacterial drugs based on oligomycin A and its derivatives.