title: Suramin blocks interaction between human FGF1 and FGFR2 D2 domain and reduces downstream signaling activity.
abstract: The extracellular portion of the human fibroblast growth factor receptor2 D2 domain (FGFR2 D2) interacts with human fibroblast growth factor 1 (hFGF1) to activate a downstream signaling cascade that ultimately affects mitosis and differentiation. Suramin is an antiparasiticdrug and a potent inhibitor of FGF-induced angiogenesis. Suramin has been shown to bind to hFGF1, and might block the interaction between hFGF1 and FGFR2 D2. Here, we titrated hFGF1 with FGFR2 D2 and suramin to elucidate their interactions using the detection of NMR. The docking results of both hFGF1-FGFR2 D2 domain and hFGF1-suramin complex were superimposed. The results indicate that suramin blocks the interaction between hFGF1 and FGFR2 D2. We used the PyMOL software to show the hydrophobic interaction of hFGF1-suramin. In addition, we used a Water-soluble Tetrazolium salts assay (WST1) to assess hFGF1 bioactivity. The results will be useful for the development of new antimitogenic activity drugs.
authors.affiliation: Department of Chemistry, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu 30013, Taiwan. Electronic address: gary810426@hotmail.com.
authors.forename: Zong-Sian
authors.initials: ZS
authors.lastname: Wu
authors.affiliation: Department of Chemistry, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu 30013, Taiwan. Electronic address: s9823002@m98.nthu.edu.tw.
authors.forename: Che Fu
authors.initials: CF
authors.lastname: Liu
authors.affiliation: Northwood High School, Irvine, CA, USA. Electronic address: brianfu9@gmail.com.
authors.forename: Brian
authors.initials: B
authors.lastname: Fu
authors.affiliation: Graduate Institute of Cancer Biology and Center for Molecular Medicine, China Medical University, No.91, Hsueh-Shih Road, Taichung 40402, Taiwan; Department of Biotechnology, Asia University, Taiwan. Electronic address: rhchou@mail.cmu.edu.tw.
authors.forename: Ruey-Hwang
authors.initials: RH
authors.lastname: Chou
authors.affiliation: Department of Chemistry, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu 30013, Taiwan. Electronic address: cyu.nthu@gmail.com.
authors.forename: Chin
authors.initials: C
authors.lastname: Yu
mesh_terms: D000977:Antiparasitic Agents; D001665:Binding Sites / Q000187:drug effects; D015536:Down-Regulation; D016220:Fibroblast Growth Factor 1 / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D061986:MCF-7 Cells; D062105:Molecular Docking Simulation; D011485:Protein Binding / Q000187:drug effects; D000072417:Protein Domains / Q000187:drug effects; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000737:chemistry* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013498:Suramin / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000977:Antiparasitic Agents; D016220:Fibroblast Growth Factor 1; D013498:Suramin; C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2
keywords: Fibroblast growth factor (FGF); Fibroblast growth factor receptor (FGFR); HADDOCK; NMR solution structure; Protein purification; Protein-ligand interaction; Suramin; WST-1 assay