4OEE

Crystal Structure Analysis of FGF2-Disaccharide (S3I2) complex

4OEE の概要

• エントリーDOI: 10.2210/pdb4oee/pdb
• 関連するPDBエントリー: 4OEF 4OEG
• 分子名称: Fibroblast growth factor 2, 2-deoxy-3-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranose-(1-4)-1-O-methyl-2-O-sulfo-alpha-L-idopyranuronic acid (3 entities in total)
• 機能のキーワード: heparin/heparin sulfate binding, protein binding
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 17859.24

構造登録者

Li, Y.C.,Hsiao, C.D. (登録日: 2014-01-13, 公開日: 2014-07-09, 最終更新日: 2023-09-20)

主引用文献

Li, Y.C.,Ho, I.H.,Ku, C.C.,Zhong, Y.Q.,Hu, Y.P.,Chen, Z.G.,Chen, C.Y.,Lin, W.C.,Zulueta, M.M.,Hung, S.C.,Lin, M.G.,Wang, C.C.,Hsiao, C.D.
Interactions that influence the binding of synthetic heparan sulfate based disaccharides to fibroblast growth factor-2.
Acs Chem.Biol., 9:1712-1717, 2014

PubMed 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.

PubMed: 24959968
DOI: 10.1021/cb500298q

実験手法

X-RAY DIFFRACTION (1.5 Å)