3F9N

Crystal structure of chk1 kinase in complex with inhibitor 38

3F9N の概要

• エントリーDOI: 10.2210/pdb3f9n/pdb
• 分子名称: Serine/threonine-protein kinase Chk1, 3-(3-chlorophenyl)-2-({(1S)-1-[(6S)-2,8-diazaspiro[5.5]undec-2-ylcarbonyl]pentyl}sulfanyl)quinazolin-4(3H)-one, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: chek1, chk1, kinase, cell cycle checkpoint, atp-binding, cytoplasm, dna damage, dna repair, nucleotide-binding, nucleus, phosphoprotein, polymorphism, serine/threonine-protein kinase, transferase, ubl conjugation
• 由来する生物種: Homo sapiens
• 細胞内の位置: Nucleus: O14757
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 37522.21

構造登録者

Yan, Y.,Munshi, S.,Ikuta, M. (登録日: 2008-11-14, 公開日: 2009-01-20, 最終更新日: 2023-09-06)

主引用文献

Converso, A.,Hartingh, T.,Garbaccio, R.M.,Tasber, E.,Rickert, K.,Fraley, M.E.,Yan, Y.,Kreatsoulas, C.,Stirdivant, S.,Drakas, B.,Walsh, E.S.,Hamilton, K.,Buser, C.A.,Mao, X.,Abrams, M.T.,Beck, S.C.,Tao, W.,Lobell, R.,Sepp-Lorenzino, L.,Zugay-Murphy, J.,Sardana, V.,Munshi, S.K.,Jezequel-Sur, S.M.,Zuck, P.D.,Hartman, G.D.
Development of thioquinazolinones, allosteric Chk1 kinase inhibitors.
Bioorg.Med.Chem.Lett., 19:1240-1244, 2009

PubMed Abstract: A high throughput screening campaign was designed to identify allosteric inhibitors of Chk1 kinase by testing compounds at high concentration. Activity was then observed at K(m) for ATP and at near-physiological concentrations of ATP. This strategy led to the discovery of a non-ATP competitive thioquinazolinone series which was optimized for potency and stability. An X-ray crystal structure for the complex of our best inhibitor bound to Chk1 was solved, indicating that it binds to an allosteric site approximately 13A from the ATP binding site. Preliminary data is presented for several of these compounds.

PubMed: 19155174
DOI: 10.1016/j.bmcl.2008.12.076

実験手法

X-RAY DIFFRACTION (1.9 Å)