| The biological activities of fibroblast growth factors (FGFs) are profoundly influenced by interactions with heparin-like molecules. Crystal structures of basic FGF (bFGF) complexed with heparin-derived tetra- and hexa-saccharides have been determined at resolutions of 1.9A and 2.2A, respectively. Both heparin fragments bind in similar fashions to a region of the bFGF surface containing residues Asn-28, Arg-121, Lys-126, and Gln-135; the heparin hexamer additionally interacts with an adjacent site formed by Lys-27, Asn-102, and Lys-136. No significant conformational change in bFGF occurs upon heparin binding, suggesting that heparin serves to facilitate the juxtaposition of components of the FGF signal transduction pathway. Comparison of the binding sites for various anions to bFGF indicates that while many anions bind to this general region of bFGF, a wide variation in specific binding interactions can be achieved. Combined with sequence variability in this region between different members of the FGF family, it is likely that a diverse set of binding interactions between FGFs and heparin-like molecules occur, which may be reflected in the differing responses and requirements for these sulfated polysaccharides exhibited by the FGF family.;Replacement of the cysteine at position 112 of Pseudomonas aeruginosa azurin with an aspartic acid residue results in a mutant (Cys112Asp) protein that retains a strong copper binding site. Cu;Keratinocyte growth factor (KGF) is a member of the fibroblast growth factors (FGF) protein family, which stimulate the proliferation and differentiation of a variety of cell types. The crystal structure of KGF has been solved at 2.4 A resolution by molecular replacement, using basic fibroblast growth factor (bFGF) as a starting model. The model refined to a final R factor of 21.0 and R... |
