4NKA

Crystal structure of human fibroblast growth factor receptor 1 kinase domain in complex with pyrazolaminopyrimidine 2

4NKA の概要

• エントリーDOI: 10.2210/pdb4nka/pdb
• 関連するPDBエントリー: 4F63 4F64 4F65 4NK9 4NKS
• 分子名称: Fibroblast growth factor receptor 1, SULFATE ION, 1,2-ETHANEDIOL, ... (5 entities in total)
• 機能のキーワード: kinase, atp binding, phosphorylation, trans-membrane, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cell 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: 71616.03

構造登録者

Norman, R.A.,Klein, T. (登録日: 2013-11-12, 公開日: 2013-12-18, 最終更新日: 2024-02-28)

主引用文献

Klein, T.,Tucker, J.,Holdgate, G.A.,Norman, R.A.,Breeze, A.L.
FGFR1 Kinase Inhibitors: Close Regioisomers Adopt Divergent Binding Modes and Display Distinct Biophysical Signatures.
ACS Med Chem Lett, 5:166-171, 2014

PubMed Abstract: The binding of a ligand to its target protein is often accompanied by conformational changes of both the protein and the ligand. This is of particular interest, since structural rearrangements of the macromolecular target and the ligand influence the free energy change upon complex formation. In this study, we use X-ray crystallography, isothermal titration calorimetry, and surface-plasmon resonance biosensor analysis to investigate the binding of pyrazolylaminopyrimidine inhibitors to FGFR1 tyrosine kinase, an important anticancer target. Our results highlight that structurally close analogs of this inhibitor series interact with FGFR1 with different binding modes, which are a consequence of conformational changes in both the protein and the ligand as well as the bound water network. Together with the collected kinetic and thermodynamic data, we use the protein-ligand crystal structure information to rationalize the observed inhibitory potencies on a molecular level.

PubMed: 24900792
DOI: 10.1021/ml4004205

実験手法

X-RAY DIFFRACTION (2.19 Å)