7RQB

Crystal structure of the Thermus thermophilus 70S ribosome in complex with protein Y, A-site aminoacyl-tRNA analog ACC-PMN, and P-site MAI-tripeptidyl-tRNA analog ACCA-IAM at 2.45A resolution

これはPDB形式変換不可エントリーです。

7RQB の概要

• エントリーDOI: 10.2210/pdb7rqb/pdb
• 分子名称: 23S Ribosomal RNA, 50S ribosomal protein L14, 50S ribosomal protein L15, ... (62 entities in total)
• 機能のキーワード: chloramphenicol, linezolid, antibiotic, peptidyl-trna, 70s ribosome, inhibition of translation, uncompetitive inhibition, peptidyl transferase center, context-specificity of drug action, ribosome
• 由来する生物種: Escherichia coli K-12; 詳細
• タンパク質・核酸の鎖数: 112
• 化学式量合計: 4431039.04

構造登録者

Syroegin, E.A.,Flemmich, L.,Klepacki, D.,Vazquez-Laslop, N.,Micura, R.,Polikanov, Y.S. (登録日: 2021-08-06, 公開日: 2022-01-26, 最終更新日: 2023-11-15)

主引用文献

Syroegin, E.A.,Flemmich, L.,Klepacki, D.,Vazquez-Laslop, N.,Micura, R.,Polikanov, Y.S.
Structural basis for the context-specific action of the classic peptidyl transferase inhibitor chloramphenicol.
Nat.Struct.Mol.Biol., 29:152-161, 2022

PubMed Abstract: Ribosome-targeting antibiotics serve as powerful antimicrobials and as tools for studying the ribosome, the catalytic peptidyl transferase center (PTC) of which is targeted by many drugs. The classic PTC-acting antibiotic chloramphenicol (CHL) and the newest clinically significant linezolid (LZD) were considered indiscriminate inhibitors of protein synthesis that cause ribosome stalling at every codon of every gene being translated. However, recent discoveries have shown that CHL and LZD preferentially arrest translation when the ribosome needs to polymerize particular amino acid sequences. The molecular mechanisms that underlie the context-specific action of ribosome inhibitors are unknown. Here we present high-resolution structures of ribosomal complexes, with or without CHL, carrying specific nascent peptides that support or negate the drug action. Our data suggest that the penultimate residue of the nascent peptide directly modulates antibiotic affinity to the ribosome by either establishing specific interactions with the drug or by obstructing its proper placement in the binding site.

PubMed: 35165455
DOI: 10.1038/s41594-022-00720-y

実験手法

X-RAY DIFFRACTION (2.45 Å)