Suramin Blocks Interaction between Human FGF1 and FGFR2 D2 Domain and Reduces Downstream Signaling Activity

• Main Authors: Wu, Zong Sian, 吳宗憲
• Other Authors: Yu, Chin
• Format: Others
• Language: zh-TW
• Published: 2016
• Online Access: http://ndltd.ncl.edu.tw/handle/12532644787760410182

碩士 === 國立清華大學 === 化學系 === 104 === The human fibroblast growth factor (hFGF) family has a high degree of structural similarity. hFGFs have been classified into 22 subcategories. FGFs are β-sheet proteins which has extensive of pathological and physiological activity of the proteins. The extracellular portion of hFGF1 interacts with FGFR2 D2, generating three common downstream signaling cascades that ultimately affects mitosis and differentiation. Suramin is an antiparasitic drug and a potent inhibitor of FGF-induced angiogenesis. Suramin has been shown to bind to hFGF1, blocking the interaction between hFGF1 and FGFR2 D2. In this study, we used Varian 700 MHz NMR to titrate hFGF1 with FGFR2 D2 and suramin to elucidate their interactions and binding constant. From HSQC and ITC data, we can know the residues of protein-protein binding regions and the interaction between protein-protein and protein-drug respectively. We further use HADDOCK to calculate protein-protein and protein-drug complex model. Then docking results of both hFGF1-FGFR2 D2 domain and hFGF1-suramin complex were superimposed and further analyzed. We used the PyMOL software to prove the electrostatic interaction of hFGF1-suramin. In addition, we used a Water-soluble Tetrazolium salts assay (WST1) to assess hFGF1 bioactivity. Based on our findings, the results will be useful for synthesis the derivatives of drug and the development of new antimitogenic activity drugs.