6HHQ

Crystal structure of compound C45 bound to the yeast 80S ribosome

これはPDB形式変換不可エントリーです。

6HHQ の概要

• エントリーDOI: 10.2210/pdb6hhq/pdb
• 分子名称: 25S ribosomal RNA, 60S ribosomal protein L8-A, 60S ribosomal protein L9-A, ... (86 entities in total)
• 機能のキーワード: 80s ribosome, inhibitor, anti-cancer, ribosome
• 由来する生物種: Saccharomyces cerevisiae; 詳細
• タンパク質・核酸の鎖数: 159
• 化学式量合計: 6646164.98

構造登録者

Pellegrino, S.,Vanderwal, C.D.,Yusupov, M. (登録日: 2018-08-28, 公開日: 2019-02-20, 最終更新日: 2024-05-15)

主引用文献

Pellegrino, S.,Meyer, M.,Konst, Z.A.,Holm, M.,Voora, V.K.,Kashinskaya, D.,Zanette, C.,Mobley, D.L.,Yusupova, G.,Vanderwal, C.D.,Blanchard, S.C.,Yusupov, M.
Understanding the role of intermolecular interactions between lissoclimides and the eukaryotic ribosome.
Nucleic Acids Res., 47:3223-3232, 2019

PubMed Abstract: Natural products that target the eukaryotic ribosome are promising therapeutics to treat a variety of cancers. It is therefore essential to determine their molecular mechanism of action to fully understand their mode of interaction with the target and to inform the development of new synthetic compounds with improved potency and reduced cytotoxicity. Toward this goal, we have previously established a short synthesis pathway that grants access to multiple congeners of the lissoclimide family. Here we present the X-ray co-crystal structure at 3.1 Å resolution of C45, a potent congener with two A-ring chlorine-bearing stereogenic centers with 'unnatural' configurations, with the yeast 80S ribosome, intermolecular interaction energies of the C45/ribosome complex, and single-molecule FRET data quantifying the impact of C45 on both human and yeast ribosomes. Together, these data provide new insights into the role of unusual non-covalent halogen bonding interactions involved in the binding of this synthetic compound to the 80S ribosome.

PubMed: 30759226
DOI: 10.1093/nar/gkz053

実験手法

X-RAY DIFFRACTION (3.10000049683 Å)