4J23

Low resolution crystal structure of the FGFR2D2D3/FGF1/SR128545 complex

4J23 の概要

• エントリーDOI: 10.2210/pdb4j23/pdb
• 分子名称: Fibroblast growth factor receptor 2, Fibroblast growth factor 1 (2 entities in total)
• 機能のキーワード: protein-protein complex, immunoglobulin c-2 type, receptor domain, fgf binding, transferase, protein binding, membrane protein, signaling protein, signaling protein-transferase complex, signaling protein/transferase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 40630.00

構造登録者

Kudlinzki, D.,Saxena, K.,Sreeramulu, S.,Schieborr, U.,Dreyer, M.,Schreuder, H.,Schwalbe, H. (登録日: 2013-02-04, 公開日: 2014-02-19, 最終更新日: 2024-11-06)

主引用文献

Herbert, C.,Schieborr, U.,Saxena, K.,Juraszek, J.,De Smet, F.,Alcouffe, C.,Bianciotto, M.,Saladino, G.,Sibrac, D.,Kudlinzki, D.,Sreeramulu, S.,Brown, A.,Rigon, P.,Herault, J.P.,Lassalle, G.,Blundell, T.L.,Rousseau, F.,Gils, A.,Schymkowitz, J.,Tompa, P.,Herbert, J.M.,Carmeliet, P.,Gervasio, F.L.,Schwalbe, H.,Bono, F.
Molecular mechanism of SSR128129E, an extracellularly acting, small-molecule, allosteric inhibitor of FGF receptor signaling.
Cancer Cell, 23:489-501, 2013

PubMed Abstract: The fibroblast growth factor (FGF)/fibroblast growth factor receptor (FGFR) signaling network plays an important role in cell growth, survival, differentiation, and angiogenesis. Deregulation of FGFR signaling can lead to cancer development. Here, we report an FGFR inhibitor, SSR128129E (SSR), that binds to the extracellular part of the receptor. SSR does not compete with FGF for binding to FGFR but inhibits FGF-induced signaling linked to FGFR internalization in an allosteric manner, as shown by crystallography studies, nuclear magnetic resonance, Fourier transform infrared spectroscopy, molecular dynamics simulations, free energy calculations, structure-activity relationship analysis, and FGFR mutagenesis. Overall, SSR is a small molecule allosteric inhibitor of FGF/FGFR signaling, acting via binding to the extracellular part of the FGFR.

PubMed: 23597563
DOI: 10.1016/j.ccr.2013.02.018

実験手法

X-RAY DIFFRACTION (3.882 Å)