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-Structure paper
| タイトル | Discovery of C13-Aminobenzoyl Cycloheximide Derivatives that Potently Inhibit Translation Elongation. |
|---|---|
| ジャーナル・号・ページ | J Am Chem Soc, Vol. 143, Issue 34, Page 13473-13477, Year 2021 |
| 掲載日 | 2021年9月1日 |
著者 | Yumi Koga / Eileen M Hoang / Yongho Park / Alexander F A Keszei / Jason Murray / Sichen Shao / Brian B Liau / ![]() |
| PubMed 要旨 | 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 ...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. |
リンク | J Am Chem Soc / PubMed:34403584 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 3.2 - 4.1 Å |
| 構造データ | EMDB-23785, PDB-7mdz: ![]() EMDB-23787: |
| 化合物 | ![]() ChemComp-MG: ![]() ChemComp-ZN: ![]() ChemComp-Z2V: |
| 由来 |
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キーワード | RIBOSOME / 80S mammalian ribosome / translation inhibitor |
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