Inhibition of Eukaryotic Translation by the Antitumor Natural Product Agelastatin A
文献类型：期刊论文
| 作者 | McClary, Brandon1,2; Zinshteyn, Boris3,4; Meyer, Melanie5; Jouanneau, Morgan6; Pellegrino, Simone5; Yusupova, Gulnara5; Schuller, Anthony3,4; Reyes, Jeremy Chris P.10; Lu, Junyan7; Guo, Zufeng1,2 |
| 刊名 | CELL CHEMICAL BIOLOGY
 |
| 出版日期 | 2017-05-18 |
| 卷号 | 24期号:5页码:605-+ |
| ISSN号 | 2451-9448 |
| DOI | 10.1016/j.chembiol.2017.04.006 |
| 文献子类 | Article |
| 英文摘要 | Protein synthesis plays an essential role in cell proliferation, differentiation, and survival. Inhibitors of eukaryotic translation have entered the clinic, establishing the translation machinery as a promising target for chemotherapy. A recently discovered, structurally unique marine sponge-derived brominated alkaloid, (-)- agelastatin A (AglA), possesses potent antitumor activity. Its underlying mechanism of action, however, has remained unknown. Using a systematic top-down approach, we show that AglA selectively inhibits protein synthesis. Using a high-throughput chemical footprinting method, we mapped the AglA-binding site to the ribosomal A site. A 3.5 angstrom crystal structure of the 80S eukaryotic ribosome from S. cerevisiae in complex with AglA was obtained, revealing multiple conformational changes of the nucleotide bases in the ribosome accompanying the binding of AglA. Together, these results have unraveled the mechanism of inhibition of eukaryotic translation by AglA at atomic level, paving the way for future structural modifications to develop AglA analogs into novel anticancer agents. |
| WOS关键词 | PROTEIN-SYNTHESIS ; (-)-AGELASTATIN ALKALOIDS ; DNA-REPLICATION ; PATEAMINE-A ; IN-VIVO ; INITIATION ; RIBOSOME ; RNA ; LEUKEMIA ; ANALOGS |
| 资助项目 | Flight Attendant Medical Research Institute (FAMRI)[00000000] ; NIH sub-contract from Baylor[R37 GM052964] ; NIH[R37 GM052964] ; NIH[GM059425] ; Welch Foundation[AA-1280] ; HHMI[00000000] ; NRSA from the NIH National Center for Complementary and Integrative Health[5F31AT008324-02] ; French National Research Agency[ANR-15-CE11-0021-01] ; European Research Council[294312] ; Russian Government Program of Competitive Growth of Kazan Federal University[00000000] |
| WOS研究方向 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000402418300015 |
| 出版者 | CELL PRESS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272659]  |
| 专题 | 药物发现与设计中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Romo, Daniel; Yusupov, Marat; Green, Rachel; Liu, Jun O. |
| 作者单位 | 1.Johns Hopkins Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA; 2.Johns Hopkins Sch Med, SJ Yan & HJ Mao Lab Chem Biol, Baltimore, MD 21205 USA; 3.Johns Hopkins Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA; 4.Howard Hughes Med Inst, Baltimore, MD 21205 USA; 5.CNRS, INSERM, UMR 7104, IGBMC,U964, F-67404 Illkirch Graffenstaden, France; 6.Baylor Univ, Dept Chem & Biochem, Waco, TX 76706 USA; 7.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai 200032, Peoples R China; 8.Fudan Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Minist Educ,Key Lab Metab & Mol Med, Shanghai 200032, Peoples R China; 9.Johns Hopkins Sch Med, Dept Oncol, Baltimore, MD 21205 USA; 10.Texas A&M Univ, Dept Chem, College Stn, TX 77842 USA |
| 推荐引用方式 GB/T 7714 | McClary, Brandon,Zinshteyn, Boris,Meyer, Melanie,et al. Inhibition of Eukaryotic Translation by the Antitumor Natural Product Agelastatin A[J]. CELL CHEMICAL BIOLOGY,2017,24(5):605-+. |
| APA | McClary, Brandon.,Zinshteyn, Boris.,Meyer, Melanie.,Jouanneau, Morgan.,Pellegrino, Simone.,...&Liu, Jun O..(2017).Inhibition of Eukaryotic Translation by the Antitumor Natural Product Agelastatin A.CELL CHEMICAL BIOLOGY,24(5),605-+. |
| MLA | McClary, Brandon,et al."Inhibition of Eukaryotic Translation by the Antitumor Natural Product Agelastatin A".CELL CHEMICAL BIOLOGY 24.5(2017):605-+. |
入库方式： OAI收割
来源：上海药物研究所
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