7RH7

Mycobacterial CIII2CIV2 supercomplex, Telacebec (Q203) bound

7RH7 の概要

• エントリーDOI: 10.2210/pdb7rh7/pdb
• EMDBエントリー: 24455 24456 24457
• 分子名称: LpqE protein, Cytochrome bc1 complex cytochrome c subunit, Cytochrome bc1 complex cytochrome b subunit, ... (24 entities in total)
• 機能のキーワード: electron transport chain, ciii2civ2 supercomplex, membrane protein
• 由来する生物種: Mycolicibacterium smegmatis MC2 155; 詳細
• タンパク質・核酸の鎖数: 24
• 化学式量合計: 713342.31

構造登録者

Di Trani, J.M.,Yanofsky, D.J.,Rubinstein, J.L. (登録日: 2021-07-16, 公開日: 2021-08-04, 最終更新日: 2025-05-28)

主引用文献

Yanofsky, D.J.,Di Trani, J.M.,Krol, S.,Abdelaziz, R.,Bueler, S.A.,Imming, P.,Brzezinski, P.,Rubinstein, J.L.
Structure of mycobacterial CIII 2 CIV 2 respiratory supercomplex bound to the tuberculosis drug candidate telacebec (Q203).
Elife, 10:-, 2021

PubMed Abstract: The imidazopyridine telacebec, also known as Q203, is one of only a few new classes of compounds in more than 50 years with demonstrated antituberculosis activity in humans. Telacebec inhibits the mycobacterial respiratory supercomplex composed of complexes III and IV (CIIICIV). In mycobacterial electron transport chains, CIIICIV replaces canonical CIII and CIV, transferring electrons from the intermediate carrier menaquinol to the final acceptor, molecular oxygen, while simultaneously transferring protons across the inner membrane to power ATP synthesis. We show that telacebec inhibits the menaquinol:oxygen oxidoreductase activity of purified CIIICIV at concentrations similar to those needed to inhibit electron transfer in mycobacterial membranes and growth in culture. We then used electron cryomicroscopy (cryoEM) to determine structures of CIIICIV both in the presence and absence of telacebec. The structures suggest that telacebec prevents menaquinol oxidation by blocking two different menaquinol binding modes to prevent CIIICIV activity.

PubMed: 34590581
DOI: 10.7554/eLife.71959

実験手法

ELECTRON MICROSCOPY (3 Å)