7y5b › Citations

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

Wong CF, Saw WG, Basak S, Sano M, Ueno H, Kerk HW, Litty D, Ragunathan P, Dick T, Müller V, Noji H, Grüber G
Antimicrob Agents Chemother e0105622 (2022)
Related entries: 7y5a, 7y5c, 7y5d

Cited: 2 times
EuropePMC logo PMID: 36445139

Abstract

The F1FO-ATP synthase is required for the viability of tuberculosis (TB) and nontuberculous mycobacteria (NTM) and has been validated as a drug target. Here, we present the cryo-EM structures of the Mycobacterium smegmatis F1-ATPase and the F1FO-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.

Articles - 7y5b mentioned but not cited (1)

  1. Structural Elements Involved in ATP Hydrolysis Inhibition and ATP Synthesis of Tuberculosis and Nontuberculous Mycobacterial F-ATP Synthase Decipher New Targets for Inhibitors. Wong CF, Saw WG, Basak S, Sano M, Ueno H, Kerk HW, Litty D, Ragunathan P, Dick T, Müller V, Noji H, Grüber G. Antimicrob Agents Chemother 66 e0105622 (2022)


Articles citing this publication (1)

  1. ATP binding by an F1Fo ATP synthase ε subunit is pH dependent, suggesting a diversity of ε subunit functional regulation in bacteria. Krah A, Vogelaar T, de Jong SI, Claridge JK, Bond PJ, McMillan DGG. Front Mol Biosci 10 1059673 (2023)


Quick links