1FGI

CRYSTAL STRUCTURE OF THE TYROSINE KINASE DOMAIN OF FIBROBLAST GROWTH FACTOR RECEPTOR 1 IN COMPLEX WITH SU5402 INHIBITOR

1FGI の概要

• エントリーDOI: 10.2210/pdb1fgi/pdb
• 分子名称: FGF RECEPTOR 1, 3-[(3-(2-CARBOXYETHYL)-4-METHYLPYRROL-2-YL)METHYLENE]-2-INDOLINONE (3 entities in total)
• 機能のキーワード: protein kinase, transferase, tyrosine-protein kinase, atp-binding, phosphorylation, inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Membrane; Single-pass type I membrane protein: P11362
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 71209.87

構造登録者

Mohammadi, M.,Schlessinger, J.,Hubbard, S.R. (登録日: 1997-03-22, 公開日: 1998-04-08, 最終更新日: 2024-02-07)

主引用文献

Mohammadi, M.,McMahon, G.,Sun, L.,Tang, C.,Hirth, P.,Yeh, B.K.,Hubbard, S.R.,Schlessinger, J.
Structures of the tyrosine kinase domain of fibroblast growth factor receptor in complex with inhibitors.
Science, 276:955-960, 1997

PubMed Abstract: A new class of protein tyrosine kinase inhibitors was identified that is based on an oxindole core (indolinones). Two compounds from this class inhibited the kinase activity of fibroblast growth factor receptor 1 (FGFR1) and showed differential specificity toward other receptor tyrosine kinases. Crystal structures of the tyrosine kinase domain of FGFR1 in complex with the two compounds were determined. The oxindole occupies the site in which the adenine of adenosine triphosphate binds, whereas the moieties that extend from the oxindole contact residues in the hinge region between the two kinase lobes. The more specific inhibitor of FGFR1 induces a conformational change in the nucleotide-binding loop. This structural information will facilitate the design of new inhibitors for use in the treatment of cancer and other diseases in which cell signaling by tyrosine kinases plays a crucial role in disease pathogenesis.

PubMed: 9139660
DOI: 10.1126/science.276.5314.955

実験手法

X-RAY DIFFRACTION (2.5 Å)