7Y5C

Cryo-EM structure of F-ATP synthase from Mycolicibacterium smegmatis (rotational state 2)

7Y5C の概要

• エントリーDOI: 10.2210/pdb7y5c/pdb
• EMDBエントリー: 33616
• 分子名称: ATP synthase subunit alpha, ADENOSINE-5'-TRIPHOSPHATE, ADENOSINE-5'-DIPHOSPHATE, ... (11 entities in total)
• 機能のキーワード: complex, f-atp synthase, cryo-em, mycobacteria, hydrolase
• 由来する生物種: Mycolicibacterium smegmatis; 詳細
• タンパク質・核酸の鎖数: 20
• 化学式量合計: 554246.33

構造登録者

Saw, W.-G.,Wong, C.F.,Grueber, G. (登録日: 2022-06-16, 公開日: 2022-11-23, 最終更新日: 2024-07-03)

主引用文献

Wong, C.F.,Saw, W.G.,Basak, S.,Sano, M.,Ueno, H.,Kerk, H.W.,Litty, D.,Ragunathan, P.,Dick, T.,Muller, V.,Noji, H.,Gruber, G.
Structural Elements Involved in ATP Hydrolysis Inhibition and ATP Synthesis of Tuberculosis and Nontuberculous Mycobacterial F-ATP Synthase Decipher New Targets for Inhibitors.
Antimicrob.Agents Chemother., 66:e0105622-e0105622, 2022

PubMed Abstract: The FF-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 F-ATPase and the FF-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.

PubMed: 36445139
DOI: 10.1128/aac.01056-22

実験手法

ELECTRON MICROSCOPY (4.7 Å)