FS23 binds to the N-terminal domain of human Hsp90: A novel small inhibitor for Hsp90
FS23 binds to the N-terminal domain of human Hsp90: A novel small inhibitor for Hsp90
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FS23 与人 Hsp90 的 N 端结构域结合：一种新型的 Hsp90 小型抑制剂
DOI：
10.13538/j.1001-8042/nst.26.060503
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发表时间：
2015-12-01
影响因子：
2.8
通讯作者：
He Jian-Hua
中科院分区：
文献类型：
--
作者：
Li Jian;Shi Feng;He Jian-Hua
热休克蛋白90（Hsp90(N)）的N端结构域负责Hsp90的催化活性。已报道的Hsp90抑制剂与该结构域结合并抑制肿瘤的生长和进展。本文合成了hsp90的小分子抑制剂FS23，并采集了hsp90 -FS23复合晶体的x射线衍射数据。高分辨率x射线晶体学显示，FS23与Hsp90(N)在核苷酸结合间隙处相互作用，这表明FS23可能与Hsp90(N)的核苷酸结合完成。Hsp90(N)与FS23的晶体结构及相互作用为新型抗肿瘤药物的设计提供了合理依据。
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.