肝纤维化是由胶原和非胶原在肝脏异常沉积引起,目前尚无特效治疗药物。热休克蛋白47(heat shock protein 47,HSP47)是一种存在于内质网中的胶原特异性分子伴侣,已被证实主要来源于纤维生成细胞,可协助三螺旋胶原前分子的正确折叠和稳定...肝纤维化是由胶原和非胶原在肝脏异常沉积引起,目前尚无特效治疗药物。热休克蛋白47(heat shock protein 47,HSP47)是一种存在于内质网中的胶原特异性分子伴侣,已被证实主要来源于纤维生成细胞,可协助三螺旋胶原前分子的正确折叠和稳定。在肝纤维化进程中,细胞外基质的主要来源是肝星状细胞,体内外研究均证实HSP47在肝内主要存在于肝星状细胞中,通过转化生长因子-β1(transforming growth factor-β1,TGF-β1)信号转导通路调控肝纤维化的发生,miRNA、HSP47-蛋白相互作用也参与了肝纤维化的发生发展,本文将对HSP47与肝纤维化的发病机制进行综述。展开更多
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 s...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 Nat 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 Nand FS23 suggest a rational basis for the design of novel antitumor drugs.展开更多
基金Supported by National Natural Science Foundation of China(No.81402850)the Natural Science Basic Research Plan in Shaanxi Province of China(No.2015JM3114)+1 种基金the Introduced talents Foundation of Xi’an Medical University(No.2015 RCYJ01)the Doctorate Foundation of Xi’an Medical University(No.2015 DOC23)
文摘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 Nat 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 Nand FS23 suggest a rational basis for the design of novel antitumor drugs.
