6XQD

Crystal structure of the Thermus thermophilus 70S ribosome in complex with sarecycline, UUC-mRNA, and deacylated P-site tRNA at 2.80A resolution

これはPDB形式変換不可エントリーです。

6XQD の概要

• エントリーDOI: 10.2210/pdb6xqd/pdb
• 分子名称: 23S Ribosomal RNA, 50S ribosomal protein L14, 50S ribosomal protein L15, ... (59 entities in total)
• 機能のキーワード: sarecycline; tetracycline; antibiotic; 70s ribosome; x-ray structure; inhibition of translation; decoding center; acne vulgaris, ribosome
• 由来する生物種: Escherichia coli; 詳細
• タンパク質・核酸の鎖数: 108
• 化学式量合計: 4470354.54

構造登録者

Batool, Z.,Lomakin, I.B.,Bunick, C.G.,Polikanov, Y.S. (登録日: 2020-07-09, 公開日: 2020-08-05, 最終更新日: 2025-03-19)

主引用文献

Batool, Z.,Lomakin, I.B.,Polikanov, Y.S.,Bunick, C.G.
Sarecycline interferes with tRNA accommodation and tethers mRNA to the 70S ribosome.
Proc.Natl.Acad.Sci.USA, 117:20530-20537, 2020

PubMed Abstract: Sarecycline is a new narrow-spectrum tetracycline-class antibiotic approved for the treatment of acne vulgaris. Tetracyclines share a common four-ring naphthacene core and inhibit protein synthesis by interacting with the 70S bacterial ribosome. Sarecycline is distinguished chemically from other tetracyclines because it has a 7-[[methoxy(methyl)amino]methyl] group attached at the C7 position of ring D. To investigate the functional role of this C7 moiety, we determined the X-ray crystal structure of sarecycline bound to the 70S ribosome. Our 2.8-Å resolution structure revealed that sarecycline binds at the canonical tetracycline binding site located in the decoding center of the small ribosomal subunit. Importantly, unlike other tetracyclines, the unique C7 extension of sarecycline extends into the messenger RNA (mRNA) channel to form a direct interaction with the A-site codon to possibly interfere with mRNA movement through the channel and/or disrupt A-site codon-anticodon interaction. Based on our biochemical studies, sarecycline appears to be a more potent initiation inhibitor compared to other tetracyclines, possibly due to drug interactions with the mRNA, thereby blocking accommodation of the first aminoacyl transfer RNA (tRNA) into the A site. Overall, our structural and biochemical findings rationalize the role of the unique C7 moiety of sarecycline in antibiotic action.

PubMed: 32817463
DOI: 10.1073/pnas.2008671117

実験手法

X-RAY DIFFRACTION (2.8 Å)