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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. - Highlights: • The interfacial residues on hFGF1-FGFR2 D2 and hFGF1-Suramin contact surface were mapped by {sup 1}H-{sup 15}N HSQC experiments. • hFGF1-FGFR2 D2 and hFGF1-Suramin complex models were generated from NMR restraints by using HADDOCK program. • We analyzed hFGF1-Suramin complex models and found the interaction between hFGF1-Suramin is hydrophobic. • The bioactivitymore » of the hFGF1-FGFR2 D2 and hFGF1-Suramin complex was studied by using WST1 assay.« less

Authors:
 [1];  [1];  [2];  [3];  [4];  [1]
  1. Department of Chemistry, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu 30013, Taiwan (China)
  2. Northwood High School, Irvine, CA (United States)
  3. Graduate Institute of Cancer Biology and Center for Molecular Medicine, China Medical University, No.91, Hsueh-Shih Road, Taichung 40402, Taiwan (China)
  4. (China)
Publication Date:
OSTI Identifier:
22606191
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 477; Journal Issue: 4; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AMMONIUM SULFATES; EDTA; ELECTROPHORESIS; ESCHERICHIA COLI; FIBROBLASTS; FLUORIDES; GELS; GROWTH FACTORS; MASS SPECTROSCOPY; NUCLEAR MAGNETIC RESONANCE; RECEPTORS; TETRAZOLIUM

Citation Formats

Wu, Zong-Sian, E-mail: gary810426@hotmail.com, Liu, Che Fu, E-mail: s9823002@m98.nthu.edu.tw, Fu, Brian, E-mail: brianfu9@gmail.com, Chou, Ruey-Hwang, E-mail: rhchou@mail.cmu.edu.tw, Department of Biotechnology, Asia University, Taiwan, and Yu, Chin, E-mail: cyu.nthu@gmail.com. Suramin blocks interaction between human FGF1 and FGFR2 D2 domain and reduces downstream signaling activity. United States: N. p., 2016. Web. doi:10.1016/J.BBRC.2016.06.149.
Wu, Zong-Sian, E-mail: gary810426@hotmail.com, Liu, Che Fu, E-mail: s9823002@m98.nthu.edu.tw, Fu, Brian, E-mail: brianfu9@gmail.com, Chou, Ruey-Hwang, E-mail: rhchou@mail.cmu.edu.tw, Department of Biotechnology, Asia University, Taiwan, & Yu, Chin, E-mail: cyu.nthu@gmail.com. Suramin blocks interaction between human FGF1 and FGFR2 D2 domain and reduces downstream signaling activity. United States. doi:10.1016/J.BBRC.2016.06.149.
Wu, Zong-Sian, E-mail: gary810426@hotmail.com, Liu, Che Fu, E-mail: s9823002@m98.nthu.edu.tw, Fu, Brian, E-mail: brianfu9@gmail.com, Chou, Ruey-Hwang, E-mail: rhchou@mail.cmu.edu.tw, Department of Biotechnology, Asia University, Taiwan, and Yu, Chin, E-mail: cyu.nthu@gmail.com. Fri . "Suramin blocks interaction between human FGF1 and FGFR2 D2 domain and reduces downstream signaling activity". United States. doi:10.1016/J.BBRC.2016.06.149.
@article{osti_22606191,
title = {Suramin blocks interaction between human FGF1 and FGFR2 D2 domain and reduces downstream signaling activity},
author = {Wu, Zong-Sian, E-mail: gary810426@hotmail.com and Liu, Che Fu, E-mail: s9823002@m98.nthu.edu.tw and Fu, Brian, E-mail: brianfu9@gmail.com and Chou, Ruey-Hwang, E-mail: rhchou@mail.cmu.edu.tw and Department of Biotechnology, Asia University, Taiwan and Yu, Chin, E-mail: cyu.nthu@gmail.com},
abstractNote = {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. - Highlights: • The interfacial residues on hFGF1-FGFR2 D2 and hFGF1-Suramin contact surface were mapped by {sup 1}H-{sup 15}N HSQC experiments. • hFGF1-FGFR2 D2 and hFGF1-Suramin complex models were generated from NMR restraints by using HADDOCK program. • We analyzed hFGF1-Suramin complex models and found the interaction between hFGF1-Suramin is hydrophobic. • The bioactivity of the hFGF1-FGFR2 D2 and hFGF1-Suramin complex was studied by using WST1 assay.},
doi = {10.1016/J.BBRC.2016.06.149},
journal = {Biochemical and Biophysical Research Communications},
number = 4,
volume = 477,
place = {United States},
year = {Fri Sep 02 00:00:00 EDT 2016},
month = {Fri Sep 02 00:00:00 EDT 2016}
}