7MDZ

80S rabbit ribosome stalled with benzamide-CHX

これはPDB形式変換不可エントリーです。

7MDZ の概要

• エントリーDOI: 10.2210/pdb7mdz/pdb
• EMDBエントリー: 23785
• 分子名称: Ribosomal protein L8, 60S ribosomal protein L11, 60S ribosomal protein L13, ... (84 entities in total)
• 機能のキーワード: 80s mammalian ribosome, translation inhibitor, ribosome
• 由来する生物種: synthetic construct; 詳細
• タンパク質・核酸の鎖数: 81
• 化学式量合計: 3363840.22

構造登録者

Koga, Y.,Hoang, E.M.,Park, Y.,Keszei, A.F.A.,Murray, J.,Shao, S.,Liau, B.B. (登録日: 2021-04-06, 公開日: 2021-09-01, 最終更新日: 2024-11-20)

主引用文献

Koga, Y.,Hoang, E.M.,Park, Y.,Keszei, A.F.A.,Murray, J.,Shao, S.,Liau, B.B.
Discovery of C13-Aminobenzoyl Cycloheximide Derivatives that Potently Inhibit Translation Elongation.
J.Am.Chem.Soc., 143:13473-13477, 2021

PubMed Abstract: Employed for over half a century to study protein synthesis, cycloheximide (CHX, ) is a small molecule natural product that reversibly inhibits translation elongation. More recently, CHX has been applied to ribosome profiling, a method for mapping ribosome positions on mRNA genome-wide. Despite CHX's extensive use, CHX treatment often results in incomplete translation inhibition due to its rapid reversibility, prompting the need for improved reagents. Here, we report the concise synthesis of C13-amide-functionalized CHX derivatives with increased potencies toward protein synthesis inhibition. Cryogenic electron microscopy (cryo-EM) revealed that C13-aminobenzoyl CHX () occupies the same site as CHX, competing with the 3' end of E-site tRNA. We demonstrate that is superior to CHX for ribosome profiling experiments, enabling more effective capture of ribosome conformations through sustained stabilization of polysomes. Our studies identify powerful chemical reagents to study protein synthesis and reveal the molecular basis of their enhanced potency.

PubMed: 34403584
DOI: 10.1021/jacs.1c05146

実験手法

ELECTRON MICROSCOPY (3.2 Å)