4KIP

Crystal structure of mitogen-activated protein kinase 14 (P38-H5) complex with 2-(2-CHLOROPHENYL)-N-(5-(CYCLOPROPYLCARBAMOYL)-2-METHYLPHENYL)-1,3-THIAZOLE-5-CARBOXAMIDE

4KIP の概要

• エントリーDOI: 10.2210/pdb4kip/pdb
• 関連するPDBエントリー: 4KIN 4KIQ
• 分子名称: Mitogen-activated protein kinase 14, 2-(2-chlorophenyl)-N-[5-(cyclopropylcarbamoyl)-2-methylphenyl]-1,3-thiazole-5-carboxamide (3 entities in total)
• 機能のキーワード: serine/threonine-protein kinase, kinase, transferase, p38 map kinase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: Q16539
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 85033.82

構造登録者

Sack, J.S.,Tokarski, J.S. (登録日: 2013-05-02, 公開日: 2013-06-12, 最終更新日: 2024-02-28)

主引用文献

Wrobleski, S.T.,Lin, S.,Murali Dhar, T.G.,Dyckman, A.J.,Li, T.,Pitt, S.,Zhang, R.,Fan, Y.,Doweyko, A.M.,Tokarski, J.S.,Kish, K.F.,Kiefer, S.E.,Sack, J.S.,Newitt, J.A.,Witmer, M.R.,McKinnon, M.,Barrish, J.C.,Dodd, J.H.,Schieven, G.L.,Leftheris, K.
The Identification of Novel P38-Alpha Isoform Selective Kinase Inhibitors Having an Unprecedented P38-Alpha Binding Mode
Bioorg.Med.Chem.Lett., 23:4120-4126, 2013

PubMed Abstract: A novel series of p38 MAP kinase inhibitors with high selectivity for the p38α isoform over the other family members including the highly homologous p38β isoform has been identified. X-ray co-crystallographic studies have revealed an unprecedented kinase binding mode in p38α for representative analogs, 5c and 9d, in which a Leu108/Met109 peptide flip occurs within the p38α hinge region. Based on these findings, a general strategy for the rational design of additional promising p38α isoform selective inhibitors by targeting this novel binding mode is proposed.

PubMed: 23746475
DOI: 10.1016/j.bmcl.2013.05.047

実験手法

X-RAY DIFFRACTION (2.27 Å)