4TYI

Structural analysis of the human Fibroblast Growth Factor Receptor 4

4TYI の概要

• エントリーDOI: 10.2210/pdb4tyi/pdb
• 関連するPDBエントリー: 4TYE 4TYG 4TYJ
• 分子名称: Fibroblast growth factor receptor 4, 4-amino-5-fluoro-3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]quinolin-2(1H)-one (2 entities in total)
• 機能のキーワード: fibroblast growth factor receptor, kinase, transferase, dovitinib, ponatinb, proteros biostructures gmbh
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cell membrane; Single-pass type I membrane protein. Isoform 2: Secreted. Isoform 3: Cytoplasm : P22455
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 35081.49

構造登録者

Lesca, E.,Lammens, A.,Huber, R.,Augustin, M. (登録日: 2014-07-08, 公開日: 2014-09-24, 最終更新日: 2024-05-08)

主引用文献

Lesca, E.,Lammens, A.,Huber, R.,Augustin, M.
Structural analysis of the human fibroblast growth factor receptor 4 kinase.
J.Mol.Biol., 426:3744-3756, 2014

PubMed Abstract: The family of fibroblast growth factor receptors (FGFRs) plays an important and well-characterized role in a variety of pathological disorders. FGFR4 is involved in myogenesis and muscle regeneration. Mutations affecting the kinase domain of FGFR4 may cause cancer, for example, breast cancer or rhabdomyosarcoma. Whereas FGFR1-FGFR3 have been structurally characterized, the structure of the FGFR4 kinase domain has not yet been reported. In this study, we present four structures of the kinase domain of FGFR4, in its apo-form and in complex with different types of small-molecule inhibitors. The two apo-FGFR4 kinase domain structures show an activation segment similar in conformation to an autoinhibitory segment observed in the hepatocyte growth factor receptor kinase but different from the known structures of other FGFR kinases. The structures of FGFR4 in complex with the type I inhibitor Dovitinib and the type II inhibitor Ponatinib reveal the molecular interactions with different types of kinase inhibitors and may assist in the design and development of FGFR4 inhibitors.

PubMed: 25219510
DOI: 10.1016/j.jmb.2014.09.004

実験手法

X-RAY DIFFRACTION (3.4 Å)