6Y69

Cryo-EM structure of an Escherichia coli 70S ribosome in complex with antibiotic TetracenomycinX

これはPDB形式変換不可エントリーです。

6Y69 の概要

• エントリーDOI: 10.2210/pdb6y69/pdb
• EMDBエントリー: 10705
• 分子名称: 16S ribosomal RNA, 30S ribosomal protein S10, 30S ribosomal protein S11, ... (56 entities in total)
• 機能のキーワード: tetracenomycin, ribosome
• 由来する生物種: Escherichia coli (strain K12); 詳細
• タンパク質・核酸の鎖数: 54
• 化学式量合計: 2141149.23

構造登録者

Wieland, M.,Wilson, D.N. (登録日: 2020-02-26, 公開日: 2020-07-01, 最終更新日: 2024-10-16)

主引用文献

Osterman, I.A.,Wieland, M.,Maviza, T.P.,Lashkevich, K.A.,Lukianov, D.A.,Komarova, E.S.,Zakalyukina, Y.V.,Buschauer, R.,Shiriaev, D.I.,Leyn, S.A.,Zlamal, J.E.,Biryukov, M.V.,Skvortsov, D.A.,Tashlitsky, V.N.,Polshakov, V.I.,Cheng, J.,Polikanov, Y.S.,Bogdanov, A.A.,Osterman, A.L.,Dmitriev, S.E.,Beckmann, R.,Dontsova, O.A.,Wilson, D.N.,Sergiev, P.V.
Tetracenomycin X inhibits translation by binding within the ribosomal exit tunnel.
Nat.Chem.Biol., 16:1071-1077, 2020

PubMed Abstract: The increase in multi-drug resistant pathogenic bacteria is making our current arsenal of clinically used antibiotics obsolete, highlighting the urgent need for new lead compounds with distinct target binding sites to avoid cross-resistance. Here we report that the aromatic polyketide antibiotic tetracenomycin (TcmX) is a potent inhibitor of protein synthesis, and does not induce DNA damage as previously thought. Despite the structural similarity to the well-known translation inhibitor tetracycline, we show that TcmX does not interact with the small ribosomal subunit, but rather binds to the large subunit, within the polypeptide exit tunnel. This previously unappreciated binding site is located adjacent to the macrolide-binding site, where TcmX stacks on the noncanonical basepair formed by U1782 and U2586 of the 23S ribosomal RNA. Although the binding site is distinct from the macrolide antibiotics, our results indicate that like macrolides, TcmX allows translation of short oligopeptides before further translation is blocked.

PubMed: 32601485
DOI: 10.1038/s41589-020-0578-x

実験手法

ELECTRON MICROSCOPY (2.86 Å)