1PMV

The structure of JNK3 in complex with a dihydroanthrapyrazole inhibitor

1PMV の概要

• エントリーDOI: 10.2210/pdb1pmv/pdb
• 関連するPDBエントリー: 1PMN 1PMQ 1PMU
• 分子名称: Mitogen-activated protein kinase 10, 2,6-DIHYDROANTHRA/1,9-CD/PYRAZOL-6-ONE (3 entities in total)
• 機能のキーワード: map kinase, apoptosis, inhibition, selectivity, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P53779
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 42221.87

構造登録者

Scapin, G.,Patel, S.B.,Lisnock, J.,Becker, J.W.,LoGrasso, P.V. (登録日: 2003-06-11, 公開日: 2003-09-09, 最終更新日: 2023-08-16)

主引用文献

Scapin, G.,Patel, S.B.,Lisnock, J.,Becker, J.W.,LoGrasso, P.V.
The structure of JNK3 in complex with small molecule inhibitors: structural basis for potency and selectivity
Chem.Biol., 10:705-712, 2003

PubMed Abstract: The c-Jun terminal kinases (JNKs) are members of the mitogen-activated protein (MAP) kinase family and regulate signal transduction in response to environmental stress. Activation of JNK3, a neuronal-specific isoform, has been associated with neurological damage, and as such, JNK3 may represent an attractive target for the treatment of neurological disorders. The MAP kinases share between 50% and 80% sequence identity. In order to obtain efficacious and safe compounds, it is necessary to address the issues of potency and selectivity. We report here four crystal structures of JNK3 in complex with three different classes of inhibitors. These structures provide a clear picture of the interactions that each class of compound made with the kinase. Knowledge of the atomic interactions involved in these diverse binding modes provides a platform for structure-guided modification of these compounds, or the de novo design of novel inhibitors that could satisfy the need for potency and selectivity.

PubMed: 12954329
DOI: 10.1016/S1074-5521(03)00159-5

実験手法

X-RAY DIFFRACTION (2.5 Å)