Heparin structure and interactions with basic fibroblast growth factor.

S Faham; R E Hileman; J R Fromm; R J Linhardt; D C Rees

doi:10.1126/science.271.5252.1116

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Heparin structure and interactions with basic fibroblast growth factor.

S Faham·R E Hileman·J R Fromm·R J Linhardt·D C Rees

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Abstract

Crystal structures of heparin-derived tetra- and hexasaccharides complexed with basic fibroblast growth factor (bFGF) were determined at resolutions of 1.9 and 2.2 angstroms, respectively. The heparin structure may be approximated as a helical polymer with a disaccharide rotation of 174 degrees and a translation of 8.6 angstroms along the helix axis. Both molecules bound similarly to a region of the bFGF surface containing residues asparagine-28, arginine-121, lysine-126, and glutamine-135, the hexasaccharide also interacted with an additional binding site formed by lysine-27, asparagine-102, and lysine-136. No significant conformational change in bFGF occurred upon heparin oligosaccharide binding, which suggests that heparin primarily serves to juxtapose components of the FGF signal transduction pathway.

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Binding Sites Carbohydrate Conformation Carbohydrate Sequence Crystallization Crystallography, X-Ray Fibroblast Growth Factor 2 Heparin Hydrogen Bonding Models, Molecular Molecular Sequence Data Oligosaccharides Protein Conformation Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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S Faham, R E Hileman, J R Fromm, R J Linhardt, D C Rees. 1996-02-23. Heparin structure and interactions with basic fibroblast growth factor.. https://doi.org/10.1126/science.271.5252.1116

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