FS23 binds to the N-terminal domain of human Hsp90: A novel small inhibitor for Hsp90

Jian LI; Feng SHI; Dan-Qi CHEN; Hui-Ling CAO; Bing XIONG; Jing-Kang SHEN; Jian-Hua HE

doi:10.13538/j.1001-8042/nst.26.060503

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FS23 binds to the N-terminal domain of human Hsp90: A novel small inhibitor for Hsp90

NUCLEAR PHYSICS AND INTERDISCIPLINARY RESEARCH | Updated：2021-01-20

- FS23 binds to the N-terminal domain of human Hsp90: A novel small inhibitor for Hsp90
- Nuclear Science and Techniques Vol. 26, Issue 6, Article number: 060503(2015)
- Affiliations：
  
  1.Shanxi Key Laboratory of Ischemic Cardiovascular Disease; Institute of Basic & Translational Medicine, Xi’an Medical University, Xi’an 710021, China
  2.Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201204, China
  3.Department of Medicinal Chemistry, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
- Author bio：
  
  jkshen@simm.ac.cn
  hejianhua@sinap.ac.cn
- Funds：
- DOI：10.13538/j.1001-8042/nst.26.060503
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Jian LI, Feng SHI, Dan-Qi CHEN, et al. FS23 binds to the N-terminal domain of human Hsp90: A novel small inhibitor for Hsp90. [J]. Nuclear Science and Techniques 26(6):060503(2015)
DOI：

Jian LI, Feng SHI, Dan-Qi CHEN, et al. FS23 binds to the N-terminal domain of human Hsp90: A novel small inhibitor for Hsp90. [J]. Nuclear Science and Techniques 26(6):060503(2015) DOI： 10.13538/j.1001-8042/nst.26.060503.

摘要

Abstract

The N-terminal domain of heat shock protein 90 (Hsp90,N,) is responsible for the catalytic activity of Hsp90. The reported inhibitors of Hsp90 bind to this domain and would inhibit tumor growth and progression. Here, we synthesized FS23, a small molecule inhibitor of hsp90 and collected X-ray diffraction data of the complex crystal of Hsp90-FS23. High resolution X-ray crystallography shows that FS23 interacted with Hsp90,N, at the nucleotide binding cleft, and this suggests that FS23 may complete with nucleotides to bind to Hsp90,N,. The crystal structure and the interaction between Hsp90,N, and FS23 suggest a rational basis for the design of novel antitumor drugs.

关键词

Keywords

Heat shock protein 90N-terminal domainInhibitorX-ray diffractionInteractions

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