Structural Elements Involved in ATP Hydrolysis Inhibition and ATP Synthesis of Tuberculosis and Nontuberculous Mycobacterial F-ATP Synthase Decipher New Targets for Inhibitors

2022/11/29 by Chui Fann Wong, Wuan Geok Saw, Wuan-Geok Saw +10
Biochemistry, Genetics and Molecular Biology · Medicine · #ATP Synthase and ATPases Research #Pediatric Hepatobiliary Diseases and Treatments #Amoebic Infections and Treatments

paper · doi:10.1128/aac.01056-22

Abstract

-ATP synthase with different nucleotide occupation within the catalytic sites and visualize critical elements for latent ATP hydrolysis and efficient ATP synthesis. Mutational studies reveal that the extended C-terminal domain (αCTD) of subunit α is the main element for the self-inhibition mechanism of ATP hydrolysis for TB and NTM bacteria. Rotational studies indicate that the transition between the inhibition state by the αCTD and the active state is a rapid process. We demonstrate that the unique mycobacterial γ-loop and subunit δ are critical elements required for ATP formation. The data underline that these mycobacterium-specific elements of α, γ, and δ are attractive targets, providing a platform for the discovery of species-specific inhibitors.

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