Nuclear Science and Techniques

《核技术》(英文版) ISSN 1001-8042 CN 31-1559/TL     2019 Impact factor 1.556

Nuclear Science and Techniques ›› 2015, Vol. 26 ›› Issue (6): 060503 doi: 10.13538/j.1001-8042/nst.26.060503

• NUCLEAR PHYSICS AND INTERDISCIPLINARY RESEARCH • Previous Articles     Next Articles

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

LI Jian, 1, 2, SHI Feng,3, CHEN Dan-Qi,3 CAO Hui-Ling,1 XIONG Bing,3 SHEN Jing-Kang,3, HE Jian-Hua 2   

  1. 1Shanxi Key Laboratory of Ischemic Cardiovascular Disease; Institute of Basic & Translational Medicine, Xi’an Medical University, Xi’an 710021, China
    2Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201204, China
    3Department of Medicinal Chemistry, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
  • Contact: SHEN Jing-Kang, HE Jian-Hua E-mail:jkshen@simm.ac.cn; hejianhua@sinap.ac.cn
  • Supported by:

    Supported by the National Natural Science Foundation of China (No. 81402850), the Natural Science Basic Research Plan in Shaanxi Province of China (No. 2015JM3114), the Introduced talents Foundation of Xi’an Medical University (No. 2015 RCYJ01) and the Doctorate Foundation of Xi’an Medical University (No. 2015 DOC23)

LI Jian, SHI Feng, CHEN Dan-Qi, CAO Hui-Ling, XIONG Bing, SHEN Jing-Kang, HE Jian-Hua . FS23 binds to the N-terminal domain of human Hsp90: A novel small inhibitor for Hsp90.Nuclear Science and Techniques, 2015, 26(6): 060503     doi: 10.13538/j.1001-8042/nst.26.060503
Citations
Altmetrics

Abstract:

The N-terminal domain of heat shock protein 90 (Hsp90N) 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 Hsp90N at the nucleotide binding cleft, and this suggests that FS23 may complete with nucleotides to bind to Hsp90N. The crystal structure and the interaction between Hsp90N and FS23 suggest a rational basis for the design of novel antitumor drugs.

Key words: Heat shock protein 90, N-terminal domain, Inhibitor, X-ray diffraction, Interactions