4YC8

C-Helix-Out Binding of Dasatinib Analog to c-Abl Kinase

4YC8 の概要

• エントリーDOI: 10.2210/pdb4yc8/pdb
• 関連するPDBエントリー: 4YBK
• 分子名称: Tyrosine-protein kinase ABL1, 2-({6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl}amino)-N-(4-phenoxyphenyl)-1,3-thiazole-5-carboxamide, 1,2-ETHANEDIOL, ... (5 entities in total)
• 機能のキーワード: kinase, c-helix-out, transferase
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm, cytoskeleton. Isoform IB: Nucleus membrane; Lipid-anchor: P00519
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 68023.84

構造登録者

Kwarcinski, F.E.,Brandvold, K.B.,Johnson, T.J.,Phadke, S.,Meagher, J.L.,Seeliger, M.A.,Stuckey, J.A.,Soellner, M.B. (登録日: 2015-02-19, 公開日: 2016-03-02, 最終更新日: 2023-09-27)

主引用文献

Kwarcinski, F.E.,Brandvold, K.R.,Phadke, S.,Beleh, O.M.,Johnson, T.K.,Meagher, J.L.,Seeliger, M.A.,Stuckey, J.A.,Soellner, M.B.
Conformation-Selective Analogues of Dasatinib Reveal Insight into Kinase Inhibitor Binding and Selectivity.
Acs Chem.Biol., 11:1296-1304, 2016

PubMed Abstract: In the kinase field, there are many widely held tenets about conformation-selective inhibitors that have yet to be validated using controlled experiments. We have designed, synthesized, and characterized a series of kinase inhibitor analogues of dasatinib, an FDA-approved kinase inhibitor that binds the active conformation. This inhibitor series includes two Type II inhibitors that bind the DFG-out inactive conformation and two inhibitors that bind the αC-helix-out inactive conformation. Using this series of compounds, we analyze the impact that conformation-selective inhibitors have on target binding and kinome-wide selectivity.

PubMed: 26895387
DOI: 10.1021/acschembio.5b01018

実験手法

X-RAY DIFFRACTION (2.9 Å)