Discovery of FS36 as a Novel Human Hsp90 Inhibitor

doi:10.16476/j.pibb.2017.0451

	Discovery of FS36 as a Novel Human Hsp90 Inhibitor
	Li Gen 2; Lu Kai-Kai 3; Li Jian 2,4; Yin Xiu-Shan 2,5; Zhao Dong 1,6; Zhang Wan-Zhong 2
刊名	PROGRESS IN BIOCHEMISTRY AND BIOPHYSICS
	2018-07
卷号	45 期号:7 页码:736-744
关键词	heat shock protein 90 antitumor drugs inhibitor X-ray diffraction complex crystal structure
ISSN号	1000-3282
DOI	10.16476/j.pibb.2017.0451
文献子类	Article
英文摘要	The heat shock protein 90 (Hsp90) plays an important role in growth and progression of tumor cells through the appropriate folding, conformational maturation and activation of several hundred protein substrates (client proteins). Thus, Hsp90 attracts a great many of interests as a promising target for antitumor drugs which results in more than 20 inhibitors advancing to clinical trials. Here, we designed and synthesized a small molecule inhibitor: FS36 and the X-ray diffraction data of the complex crystal of Hsp90N-FS36 is collected. High-resolution X-ray crystallography shows that FS36 interacts with Hsp90(N) at the ATP-binding pocket and this demonstrates that FS36 possibly substitutes nucleotides to bind to Hsp90(N). The complex crystal structure and the interactions between FS36 and Hsp90(N) lay the foundation of the design and majorization of novel antitumor drugs.
资助项目	National Natural Science Foundation of China[81402850] ; Special Scientific Research Project of Education Department of Shaanxi Provincial Government[17JK0669]
WOS关键词	SHOCK-PROTEIN 90 ; ESCHERICHIA-COLI HSP90 ; MOLECULAR CHAPERONE ; CRYSTAL-STRUCTURE ; BINDING SITE ; DRUG TARGET ; DIMERIZATION ; REVEALS ; AGENT
WOS研究方向	Biochemistry & Molecular Biology ; Biophysics
语种	英语
CSCD记录号	CSCD:6285654
出版者	CHINESE ACAD SCIENCES, INST BIOPHYSICS
WOS记录号	WOS:000439955300005
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279678]
专题	中国科学院上海药物研究所
通讯作者	Zhang Wan-Zhong
作者单位	1.Xian Med Univ, Shaanxi Key Lab Ischem Cardiovasc Dis, Xian 710021, Shaanxi, Peoples R China; 2.Shenyang Univ Chem Technol, Coll Pharmaceut & Biol Engn, Shenyang 110142, Liaoning, Peoples R China; 3.Univ Chinese Acad Sci, Shanghai Inst Mat, Shanghai 201203, Peoples R China; 4.Univ Kentucky, Coll Med, Dept Mol & Cellular Biochem, Lexington, KY 40536 USA; 5.Karolinska Inst MTC, Sci Life Lab, Tomtebodavag 23A Gamma5, S-17165 Solna, Sweden; 6.Xian Med Univ, Inst Basic & Translat Med, Xian 710021, Shaanxi, Peoples R China
推荐引用方式 GB/T 7714	Li Gen,Lu Kai-Kai,Li Jian,et al. Discovery of FS36 as a Novel Human Hsp90 Inhibitor[J]. PROGRESS IN BIOCHEMISTRY AND BIOPHYSICS,2018,45(7):736-744.
APA	Li Gen,Lu Kai-Kai,Li Jian,Yin Xiu-Shan,Zhao Dong,&Zhang Wan-Zhong.(2018).Discovery of FS36 as a Novel Human Hsp90 Inhibitor.PROGRESS IN BIOCHEMISTRY AND BIOPHYSICS,45(7),736-744.
MLA	Li Gen,et al."Discovery of FS36 as a Novel Human Hsp90 Inhibitor".PROGRESS IN BIOCHEMISTRY AND BIOPHYSICS 45.7(2018):736-744.