7S1J

Wild-type Escherichia coli ribosome with antibiotic radezolid

これはPDB形式変換不可エントリーです。

7S1J の概要

• エントリーDOI: 10.2210/pdb7s1j/pdb
• EMDBエントリー: 24803
• 分子名称: 30S ribosomal protein S19, 23S rRNA, 5S rRNA, ... (56 entities in total)
• 機能のキーワード: oxazolidinone, radezolid, ribosome
• 由来する生物種: Escherichia coli; 詳細
• タンパク質・核酸の鎖数: 52
• 化学式量合計: 2145042.52

構造登録者

Young, I.D.,Stojkovic, V.,Tsai, K.,Lee, D.J.,Fraser, J.S.,Galonic Fujimori, D. (登録日: 2021-09-02, 公開日: 2022-03-02)

主引用文献

Tsai, K.,Stojkovic, V.,Lee, D.J.,Young, I.D.,Szal, T.,Klepacki, D.,Vazquez-Laslop, N.,Mankin, A.S.,Fraser, J.S.,Fujimori, D.G.
Structural basis for context-specific inhibition of translation by oxazolidinone antibiotics.
Nat.Struct.Mol.Biol., 29:162-171, 2022

PubMed Abstract: The antibiotic linezolid, the first clinically approved member of the oxazolidinone class, inhibits translation of bacterial ribosomes by binding to the peptidyl transferase center. Recent work has demonstrated that linezolid does not inhibit peptide bond formation at all sequences but rather acts in a context-specific manner, namely when alanine occupies the penultimate position of the nascent chain. However, the molecular basis for context-specificity has not been elucidated. Here we show that the second-generation oxazolidinone radezolid also induces stalling with a penultimate alanine, and we determine high-resolution cryo-EM structures of linezolid- and radezolid-stalled ribosome complexes to explain their mechanism of action. These structures reveal that the alanine side chain fits within a small hydrophobic crevice created by oxazolidinone, resulting in improved ribosome binding. Modification of the ribosome by the antibiotic resistance enzyme Cfr disrupts stalling due to repositioning of the modified nucleotide. Together, our findings provide molecular understanding for the context-specificity of oxazolidinones.

PubMed: 35165456
DOI: 10.1038/s41594-022-00723-9

実験手法

ELECTRON MICROSCOPY (2.47 Å)