title: Interactions that influence the binding of synthetic heparan sulfate based disaccharides to fibroblast growth factor-2.
abstract: Heparan sulfate (HS) is a linear sulfated polysaccharide that mediates protein activities at the cell-extracellular 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.
authors: Institute of Molecular Biology, ‡Genomics Research Center, and §Institute of Chemistry, Academia Sinica , Taipei 115, Taiwan.
authors: Yi-Ching
authors: YC
authors: Li
authors: I-Hsin
authors: IH
authors: Ho
authors: Chiao-Chu
authors: CC
authors: Ku
authors: Yong-Qing
authors: YQ
authors: Zhong
authors: Yu-Peng
authors: YP
authors: Hu
authors: Zhi-Geng
authors: ZG
authors: Chen
authors: Chun-Yen
authors: CY
authors: Chen
authors: Wei-Chen
authors: WC
authors: Lin
authors: Medel Manuel L
authors: MM
authors: Zulueta
authors: Shang-Cheng
authors: SC
authors: Hung
authors: Min-Guan
authors: MG
authors: Lin
authors: Cheng-Chung
authors: CC
authors: Wang
authors: Chwan-Deng
authors: CD
authors: Hsiao
mesh_terms: D018360:Crystallography, X-Ray; D004187:Disaccharides / Q000737:chemistry / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D006497:Heparan Sulfate / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular
chemical_list: D004187:Disaccharides; D016222:Fibroblast Growth Factor 2; D006497:Heparan Sulfate