6XHV

Crystal structure of the A2058-dimethylated Thermus thermophilus 70S ribosome in complex with mRNA, aminoacylated A- and P-site tRNAs, and deacylated E-site tRNA at 2.40A resolution

これはPDB形式変換不可エントリーです。

6XHV の概要

• エントリーDOI: 10.2210/pdb6xhv/pdb
• 分子名称: 23S Ribosomal RNA, 50S ribosomal protein L14, 50S ribosomal protein L15, ... (61 entities in total)
• 機能のキーワード: macrolide; antibiotic; resistance; methylation; a2058; 23s rrna; 70s ribosome; x-ray structure; inhibition of translation; peptidyl transferase center; nascent peptide exit tunnel, ribosome
• 由来する生物種: Thermus thermophilus HB8; 詳細
• タンパク質・核酸の鎖数: 112
• 化学式量合計: 4571549.77

構造登録者

Svetlov, M.S.,Syroegin, E.A.,Aleksandrova, E.V.,Atkinson, G.C.,Gregory, S.T.,Mankin, A.S.,Polikanov, Y.S. (登録日: 2020-06-19, 公開日: 2020-12-23, 最終更新日: 2023-11-15)

主引用文献

Svetlov, M.S.,Syroegin, E.A.,Aleksandrova, E.V.,Atkinson, G.C.,Gregory, S.T.,Mankin, A.S.,Polikanov, Y.S.
Structure of Erm-modified 70S ribosome reveals the mechanism of macrolide resistance.
Nat.Chem.Biol., 17:412-420, 2021

PubMed Abstract: Many antibiotics inhibit bacterial growth by binding to the ribosome and interfering with protein biosynthesis. Macrolides represent one of the most successful classes of ribosome-targeting antibiotics. The main clinically relevant mechanism of resistance to macrolides is dimethylation of the 23S rRNA nucleotide A2058, located in the drug-binding site, a reaction catalyzed by Erm-type rRNA methyltransferases. Here, we present the crystal structure of the Erm-dimethylated 70S ribosome at 2.4 Å resolution, together with the structures of unmethylated 70S ribosome functional complexes alone or in combination with macrolides. Altogether, our structural data do not support previous models and, instead, suggest a principally new explanation of how A2058 dimethylation confers resistance to macrolides. Moreover, high-resolution structures of two macrolide antibiotics bound to the unmodified ribosome reveal a previously unknown role of the desosamine moiety in drug binding, laying a foundation for the rational knowledge-based design of macrolides that can overcome Erm-mediated resistance.

PubMed: 33462493
DOI: 10.1038/s41589-020-00715-0

実験手法

X-RAY DIFFRACTION (2.4 Å)