Discovery of a novel small inhibitor RJ19 targeting to human Hsp90
文献类型：期刊论文
| 作者 | Cao, HL; Lyu, KK; Liu, B; Li, J; He, JH |
| 刊名 | NUCLEAR SCIENCE AND TECHNIQUES
 |
| 出版日期 | 2017 |
| 卷号 | 28期号:10页码:- |
| 关键词 | Shock-protein 90 Atp Hydrolysis Chaperone Identification Binding Design Agent |
| ISSN号 | 1001-8042 |
| DOI | 10.1007/s41365-017-0300-1 |
| 文献子类 | 期刊论文 |
| 英文摘要 | Heat shock protein 90 (Hsp90) can promote growth and proliferation of cancer cells by helping in folding, conformational maturation, and activation of various client proteins. Therefore, Hsp90 has been paid more attention to as an anticancer drug target. Reported Hsp90 inhibitors have several limitations such as poor solubility, limited bioavailability, and hepatotoxicity. Here, a novel small inhibitor RJ19 has been designed using fragment-based drug discovery and synthesized. Additionally, a crystal structure of Hsp90(N) -RJ19 was determined by X-ray diffraction (resolution limit, 2.0 angstrom, PDB code 4L90). The crystal structure of Hsp90(N)-RJ19 was analyzed in detail and compared with that of native Hsp90(N), Hsp90(N)-ATP, and Hsp90(N) -GDM, respectively. It was indicated that RJ19 interacted with Hsp90(N) at the ATP-binding pocket, which suggests that RJ19 may replace nucleotides to bind with Hsp90(N) to result in chaperone function failure of Hsp90. RJ19, therefore, has emerged as a promising anticancer lead compound. Rearrangement and displacement of L2 Loop in Hsp90(N)=-RJ19 play a key role in the function failure, which also makes the pocket wider and longer facilitating structure modification of RJ19 later. The complex crystal structure and interaction between RJ19 and Hsp90(N) provide a rational basis for the design and optimization of novel anticancer drugs. |
| WOS关键词 | SHOCK-PROTEIN 90 ; ATP HYDROLYSIS ; CHAPERONE ; IDENTIFICATION ; BINDING ; DESIGN ; AGENT |
| 语种 | 英语 |
| WOS记录号 | WOS:000411149700011 |
| 源URL | [http://ir.sinap.ac.cn/handle/331007/28610]  |
| 专题 | 上海应用物理研究所_中科院上海应用物理研究所2011-2017年 |
| 推荐引用方式 GB/T 7714 | Cao, HL,Lyu, KK,Liu, B,et al. Discovery of a novel small inhibitor RJ19 targeting to human Hsp90[J]. NUCLEAR SCIENCE AND TECHNIQUES,2017,28(10):-. |
| APA | Cao, HL,Lyu, KK,Liu, B,Li, J,&He, JH.(2017).Discovery of a novel small inhibitor RJ19 targeting to human Hsp90.NUCLEAR SCIENCE AND TECHNIQUES,28(10),-. |
| MLA | Cao, HL,et al."Discovery of a novel small inhibitor RJ19 targeting to human Hsp90".NUCLEAR SCIENCE AND TECHNIQUES 28.10(2017):-. |
入库方式： OAI收割
来源：上海应用物理研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。