Ornitz D M, Herr A B, Nilsson M, Westman J, Svahn C M, Waksman G
Department of Molecular Biology and Pharmacology, Washington University Medical School, St. Louis, MO 63110, USA.
Science. 1995 Apr 21;268(5209):432-6. doi: 10.1126/science.7536345.
Fibroblast growth factors (FGFs) require a polysaccharide cofactor, heparin or heparan sulfate (HS), for receptor binding and activation. To probe the molecular mechanism by which heparin or HS (heparin/HS) activates FGF, small nonsulfated oligosaccharides found within heparin/HS were assayed for activity. These synthetic and isomerically pure compounds can activate the FGF signaling pathway. The crystal structures of complexes between FGF and these heparin/HS oligosaccharides reveal several binding sites on FGF and constrain possible mechanisms by which heparin/HS can activate the FGF receptor. These studies establish a framework for the molecular design of compounds capable of modulating FGF activity.
成纤维细胞生长因子（FGFs）需要一种多糖辅因子，即肝素或硫酸乙酰肝素（HS），用于受体结合和激活。为了探究肝素或HS（肝素/HS）激活FGF的分子机制，对肝素/HS中发现的小的非硫酸化寡糖进行了活性检测。这些合成的且异构体纯的化合物能够激活FGF信号通路。FGF与这些肝素/HS寡糖之间复合物的晶体结构揭示了FGF上的几个结合位点，并限制了肝素/HS激活FGF受体的可能机制。这些研究为能够调节FGF活性的化合物的分子设计建立了一个框架。
