7LH5

Crystal structure of the Thermus thermophilus 70S ribosome in complex with plazomicin, mRNA and tRNAs

これはPDB形式変換不可エントリーです。

7LH5 の概要

• エントリーDOI: 10.2210/pdb7lh5/pdb
• 分子名称: 16S ribosomal RNA, 30S ribosomal protein S10, 30S ribosomal protein S11, ... (62 entities in total)
• 機能のキーワード: 70s ribosome, plazomicin, antibiotic resistance, aminoglycoside, ribosome
• 由来する生物種: Escherichia coli; 詳細
• タンパク質・核酸の鎖数: 118
• 化学式量合計: 4589368.96

構造登録者

Golkar, T.,Berghuis, A.M.,Schmeing, T.M. (登録日: 2021-01-21, 公開日: 2021-06-02, 最終更新日: 2024-10-30)

主引用文献

Golkar, T.,Bassenden, A.V.,Maiti, K.,Arya, D.P.,Schmeing, T.M.,Berghuis, A.M.
Structural basis for plazomicin antibiotic action and resistance.
Commun Biol, 4:729-729, 2021

PubMed Abstract: The approval of plazomicin broadened the clinical library of aminoglycosides available for use against emerging bacterial pathogens. Contrarily to other aminoglycosides, resistance to plazomicin is limited; still, instances of resistance have been reported in clinical settings. Here, we present structural insights into the mechanism of plazomicin action and the mechanisms of clinical resistance. The structural data reveal that plazomicin exclusively binds to the 16S ribosomal A site, where it likely interferes with the fidelity of mRNA translation. The unique extensions to the core aminoglycoside scaffold incorporated into the structure of plazomicin do not interfere with ribosome binding, which is analogously seen in the binding of this antibiotic to the AAC(2')-Ia resistance enzyme. The data provides a structural rationale for resistance conferred by drug acetylation and ribosome methylation, i.e., the two mechanisms of resistance observed clinically. Finally, the crystal structures of plazomicin in complex with both its target and the clinically relevant resistance factor provide a roadmap for next-generation drug development that aims to ameliorate the impact of antibiotic resistance.

PubMed: 34117352
DOI: 10.1038/s42003-021-02261-4

実験手法

X-RAY DIFFRACTION (3.27 Å)