Interactions That Influence the Binding of Synthetic Heparan Sulfate Based Disaccharides to Fibroblast Growth Factor-2

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• 作者：Yi-Ching Li ; I-Hsin Ho ; Chiao-Chu Ku ; Yong-Qing Zhong ; Yu-Peng Hu ; Zhi-Geng Chen ; Chun-Yen Chen ; Wei-Chen Lin ; Medel Manuel L. Zulueta ; Shang-Cheng Hung ; Min-Guan Lin ; Cheng-Chung Wang ; Chwan-Deng Hsiao
• 刊名：ACS Chemical Biology
• 出版年：2014
• 出版时间：August 15, 2014
• 年：2014
• 卷：9
• 期：8
• 页码：1712-1717
• 全文大小：332K
• ISSN：1554-8937

文摘

Heparan sulfate (HS) is a linear sulfated polysaccharide that mediates protein activities at the cell鈥揺xtracellular interface. Its interactions with proteins depend on the complex patterns of sulfonations and sugar residues. Previously, we synthesized all 48 potential disaccharides found in HS and used them for affinity screening and X-ray structural analysis with fibroblast growth factor-1 (FGF1). Herein, we evaluated the affinities of the same sugars against FGF2 and determined the crystal structures of FGF2 in complex with three disaccharides carrying N-sulfonated glucosamine and 2-O-sulfonated iduronic acid as basic backbones. The crystal structures show that water molecules mediate different interactions between the 3-O-sulfonate group and Lys125. Moreover, the 6-O-sulfonate group forms intermolecular interactions with another FGF2 unit apart from the main binding site. These findings suggest that the water-mediated interactions and the intermolecular interactions influence the binding affinity of different disaccharides with FGF2, correlating with their respective dissociation constants in solution.