title: Molecular level interaction of the human acidic fibroblast growth factor with the antiangiogenic agent, inositol hexaphosphate .
abstract: Acidic fibroblast growth factor (FGF1) regulates a wide array of important biological phenomena such as angiogenesis, cell differentiation, tumor growth, and neurogenesis. Generally, FGFs are known for their strong affinity for the glycosaminoglycan heparin, as a prerequisite for recognition of a specific tyrosine kinase on the cell surface and are responsible for the cell signal transduction cascade. Inositol hexaphosphate (IP6) is a natural antioxidant and is known for its antiangiogenic role, in addition to its ability to control tumor growth. In the present study, we investigated the interaction of IP6 with the acidic fibroblast growth factor (FGF1) using various biophysical techniques including isothermal calorimetry, circular dichroism, and multidimensional NMR spectroscopy. Herein, we have reported the three-dimensional solution structure of the FGF1-IP6 complex. These data show that IP6 binds FGF1 and enhances its thermal stability. In addition, we also demonstrate that IP6 acts as an antagonist to acidic fibroblast growth factor by inhibiting its receptor binding and subsequently decreasing the mitogenic activity. The inhibition likely results in the ability of IP6 to antagonize the angiogenic and mitogenic activity of FGF1.
authors.affiliation: Department of Chemistry, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Sriramoju M
authors.initials: SM
authors.lastname: Kumar
authors.forename: Han-Min
authors.initials: HM
authors.lastname: Wang
authors.forename: Sepuru K
authors.initials: SK
authors.lastname: Mohan
authors.forename: Ruey-Hwang
authors.initials: RH
authors.lastname: Chou
authors.forename: Chin
authors.initials: C
authors.lastname: Yu
mesh_terms: D020533:Angiogenesis Inhibitors / Q000378:metabolism*; D002151:Calorimetry; D002942:Circular Dichroism; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D010833:Phytic Acid / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D020533:Angiogenesis Inhibitors; D016220:Fibroblast Growth Factor 1; D010833:Phytic Acid