5AM6

Native FGFR1 with an inhibitor

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5AM6 の概要

• エントリーDOI: 10.2210/pdb5am6/pdb
• 関連するPDBエントリー: 5AM7
• 分子名称: FIBROBLAST GROWTH FACTOR RECEPTOR 1, CHLORIDE ION, 4-amino-5-fluoro-3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]quinolin-2(1H)-one, ... (4 entities in total)
• 機能のキーワード: transferase, fgfr, growth factor, cancer, dovitinib, tki258, kinase
• 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: 71508.44

構造登録者

Bunney, T.D.,Wan, S.,Thiyagarajan, N.,Sutto, L.,Williams, S.V.,Ashford, P.,Koss, H.,Knowles, M.A.,Gervasio, F.L.,Coveney, P.V.,Katan, M. (登録日: 2015-03-10, 公開日: 2015-03-18, 最終更新日: 2024-01-10)

主引用文献

Bunney, T.,Wan, S.,Thiyagarajan, N.,Sutto, L.,Williams, S.V.,Ashford, P.,Koss, H.,Knowles, M.A.,Gervasio, F.L.,Coveney, P.V.,Katan, M.
The Effect of Mutations on Drug Sensitivity and Kinase Activity of Fibroblast Growth Factor Receptors: A Combined Experimental and Theoretical Study
Ebiomedicine, 2:194-, 2015

PubMed Abstract: Fibroblast growth factor receptors (FGFRs) are recognized therapeutic targets in cancer. We here describe insights underpinning the impact of mutations on FGFR1 and FGFR3 kinase activity and drug efficacy, using a combination of computational calculations and experimental approaches including cellular studies, X-ray crystallography and biophysical and biochemical measurements. Our findings reveal that some of the tested compounds, in particular TKI258, could provide therapeutic opportunity not only for patients with primary alterations in but also for acquired resistance due to the gatekeeper mutation. The accuracy of the computational methodologies applied here shows a potential for their wider application in studies of drug binding and in assessments of functional and mechanistic impacts of mutations, thus assisting efforts in precision medicine.

PubMed: 26097890
DOI: 10.1016/J.EBIOM.2015.02.009

実験手法

X-RAY DIFFRACTION (1.96 Å)