6MYN

Crystal structure of murine NF-kappaB inducing kinase (NIK) bound to inhibitor R7

6MYN の概要

• エントリーDOI: 10.2210/pdb6myn/pdb
• 関連するPDBエントリー: 4G3C
• 分子名称: Mitogen-activated protein kinase kinase kinase 14, SULFATE ION, (5s,7s)-9-fluoro-10-[(3R)-3-hydroxy-3-(5-methyl-1,2-oxazol-3-yl)but-1-yn-1-yl]-N~3~-methyl-6,7-dihydro-5H-5,7-methanoimidazo[2,1-a][2]benzazepine-2,3-dicarboxamide, ... (4 entities in total)
• 機能のキーワード: nik, kinase, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Mus musculus (Mouse)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 78205.88

構造登録者

Harris, S.F.,Smith, M.,Barker, J. (登録日: 2018-11-01, 公開日: 2019-08-07, 最終更新日: 2024-03-13)

主引用文献

Feng, J.A.,Lee, P.,Alaoui, M.H.,Barrett, K.,Castanedo, G.,Godemann, R.,McEwan, P.,Wang, X.,Wu, P.,Zhang, Y.,Harris, S.F.,Staben, S.T.
Structure Based Design of Potent Selective Inhibitors of Protein Kinase D1 (PKD1).
Acs Med.Chem.Lett., 10:1260-1265, 2019

PubMed Abstract: We previously disclosed a series of type I 1/2 inhibitors of NF-κB inducing kinase (NIK). Inhibition of NIK by these compounds was found to be strongly dependent on the inclusion and absolute stereochemistry of a propargyl tertiary alcohol as it forms critical hydrogen bonds (H-bonds) with NIK. We report that inhibition of protein kinase D1 (PKD1) by this class of compounds is not dependent on H-bond interactions of this tertiary alcohol. This feature was leveraged in the design of highly selective inhibitors of PKD1 that no longer inhibit NIK. A structure-based hypothesis based on the position and flexibility of the α-C-helix of PKD1 vs NIK is presented.

PubMed: 31531194
DOI: 10.1021/acsmedchemlett.8b00658

実験手法

X-RAY DIFFRACTION (2.744 Å)