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Crystal Structure Analysis of FGF2-Disaccharide (S3I2) complexCrystal Structure Analysis of FGF2-Disaccharide (S3I2) complex
Structural highlights
FunctionFGF2_HUMAN Plays an important role in the regulation of cell survival, cell division, angiogenesis, cell differentiation and cell migration. Functions as potent mitogen in vitro.[1] [2] Publication Abstract from PubMedHeparan 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. Interactions That Influence the Binding of Synthetic Heparan Sulfate Based Disaccharides to Fibroblast Growth Factor-2.,Li YC, Ho IH, Ku CC, Zhong YQ, Hu YP, Chen ZG, Chen CY, Lin WC, Zulueta MM, Hung SC, Lin MG, Wang CC, Hsiao CD ACS Chem Biol. 2014 Jun 26. PMID:24959968[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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