7ZTA

Structure of an Escherichia coli 70S ribosome stalled by Tetracenomycin X during translation of an MAAAPQK(C) peptide

これはPDB形式変換不可エントリーです。

7ZTA の概要

• エントリーDOI: 10.2210/pdb7zta/pdb
• EMDBエントリー: 14956
• 分子名称: 16S ribosomal RNA, 30S ribosomal protein S10, 30S ribosomal protein S11, ... (64 entities in total)
• 機能のキーワード: antibiotic, translation, ribosome, tetracenomycin x, protein synthesis inhibitor
• 由来する生物種: Escherichia coli K-12; 詳細
• タンパク質・核酸の鎖数: 57
• 化学式量合計: 2202995.77

構造登録者

Leroy, E.C.,Perry, T.N.,Renault, T.T.,Innis, C.A. (登録日: 2022-05-09, 公開日: 2023-04-12, 最終更新日: 2024-09-25)

主引用文献

Leroy, E.C.,Perry, T.N.,Renault, T.T.,Innis, C.A.
Tetracenomycin X sequesters peptidyl-tRNA during translation of QK motifs.
Nat.Chem.Biol., 19:1091-1096, 2023

PubMed Abstract: As antimicrobial resistance threatens our ability to treat common bacterial infections, new antibiotics with limited cross-resistance are urgently needed. In this regard, natural products that target the bacterial ribosome have the potential to be developed into potent drugs through structure-guided design, provided their mechanisms of action are well understood. Here we use inverse toeprinting coupled to next-generation sequencing to show that the aromatic polyketide tetracenomycin X primarily inhibits peptide bond formation between an incoming aminoacyl-tRNA and a terminal Gln-Lys (QK) motif in the nascent polypeptide. Using cryogenic electron microscopy, we reveal that translation inhibition at QK motifs occurs via an unusual mechanism involving sequestration of the 3' adenosine of peptidyl-tRNA in the drug-occupied nascent polypeptide exit tunnel of the ribosome. Our study provides mechanistic insights into the mode of action of tetracenomycin X on the bacterial ribosome and suggests a path forward for the development of novel aromatic polyketide antibiotics.

PubMed: 37322159
DOI: 10.1038/s41589-023-01343-0

実験手法

ELECTRON MICROSCOPY (2.7 Å)