6OM6

Structure of trans-translation inhibitor bound to E. coli 70S ribosome with P site tRNA

これはPDB形式変換不可エントリーです。

6OM6 の概要

• エントリーDOI: 10.2210/pdb6om6/pdb
• EMDBエントリー: 20121
• 分子名称: 23S ribosomal RNA, 50S ribosomal protein L6, 50S ribosomal protein L9, ... (55 entities in total)
• 機能のキーワード: trans-translation, translation, antibiotic, ribosome
• 由来する生物種: Escherichia coli; 詳細
• タンパク質・核酸の鎖数: 54
• 化学式量合計: 2164378.90

構造登録者

Hoffer, E.D.,Mehrani, A.,Keiler, K.C.,Stagg, S.M.,Dunham, C.M. (登録日: 2019-04-18, 公開日: 2021-02-10, 最終更新日: 2025-03-19)

主引用文献

Aron, Z.D.,Mehrani, A.,Hoffer, E.D.,Connolly, K.L.,Srinivas, P.,Torhan, M.C.,Alumasa, J.N.,Cabrera, M.,Hosangadi, D.,Barbor, J.S.,Cardinale, S.C.,Kwasny, S.M.,Morin, L.R.,Butler, M.M.,Opperman, T.J.,Bowlin, T.L.,Jerse, A.,Stagg, S.M.,Dunham, C.M.,Keiler, K.C.
trans-Translation inhibitors bind to a novel site on the ribosome and clear Neisseria gonorrhoeae in vivo.
Nat Commun, 12:1799-1799, 2021

PubMed Abstract: Bacterial ribosome rescue pathways that remove ribosomes stalled on mRNAs during translation have been proposed as novel antibiotic targets because they are essential in bacteria and are not conserved in humans. We previously reported the discovery of a family of acylaminooxadiazoles that selectively inhibit trans-translation, the main ribosome rescue pathway in bacteria. Here, we report optimization of the pharmacokinetic and antibiotic properties of the acylaminooxadiazoles, producing MBX-4132, which clears multiple-drug resistant Neisseria gonorrhoeae infection in mice after a single oral dose. Single particle cryogenic-EM studies of non-stop ribosomes show that acylaminooxadiazoles bind to a unique site near the peptidyl-transfer center and significantly alter the conformation of ribosomal protein bL27, suggesting a novel mechanism for specific inhibition of trans-translation by these molecules. These results show that trans-translation is a viable therapeutic target and reveal a new conformation within the bacterial ribosome that may be critical for ribosome rescue pathways.

PubMed: 33741965
DOI: 10.1038/s41467-021-22012-7

実験手法

ELECTRON MICROSCOPY (3.1 Å)