6NYH

Structure of human RIPK1 kinase domain in complex with GNE684

6NYH の概要

• エントリーDOI: 10.2210/pdb6nyh/pdb
• 分子名称: Receptor-interacting serine/threonine-protein kinase 1, (5S)-N-[(3S)-7-methoxy-1-methyl-2-oxo-2,3,4,5-tetrahydro-1H-pyrido[3,4-b]azepin-3-yl]-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazole-2-carboxamide, IODIDE ION, ... (4 entities in total)
• 機能のキーワード: rip1, kinase, rip, rip1k ripk1, immune system, transferase-transferase inhibitor complex
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 68852.08

構造登録者

Fong, R.,Lupardus, P.J. (登録日: 2019-02-11, 公開日: 2019-05-29, 最終更新日: 2023-10-11)

主引用文献

Patel, S.,Webster, J.D.,Varfolomeev, E.,Kwon, Y.C.,Cheng, J.H.,Zhang, J.,Dugger, D.L.,Wickliffe, K.E.,Maltzman, A.,Sujatha-Bhaskar, S.,Bir Kohli, P.,Ramaswamy, S.,Deshmukh, G.,Liederer, B.M.,Fong, R.,Hamilton, G.,Lupardus, P.,Caplazi, P.,Lee, W.P.,van Lookeren Campagne, M.,Johnson, A.,McKenzie, B.S.,Junttila, M.R.,Newton, K.,Vucic, D.
RIP1 inhibition blocks inflammatory diseases but not tumor growth or metastases.
Cell Death Differ., 27:161-175, 2020

PubMed Abstract: The kinase RIP1 acts in multiple signaling pathways to regulate inflammatory responses and it can trigger both apoptosis and necroptosis. Its kinase activity has been implicated in a range of inflammatory, neurodegenerative, and oncogenic diseases. Here, we explore the effect of inhibiting RIP1 genetically, using knock-in mice that express catalytically inactive RIP1 D138N, or pharmacologically, using the murine-potent inhibitor GNE684. Inhibition of RIP1 reduced collagen antibody-induced arthritis, and prevented skin inflammation caused by mutation of Sharpin, or colitis caused by deletion of Nemo from intestinal epithelial cells. Conversely, inhibition of RIP1 had no effect on tumor growth or survival in pancreatic tumor models driven by mutant Kras, nor did it reduce lung metastases in a B16 melanoma model. Collectively, our data emphasize a role for the kinase activity of RIP1 in certain inflammatory disease models, but question its relevance to tumor progression and metastases.

PubMed: 31101885
DOI: 10.1038/s41418-019-0347-0

実験手法

X-RAY DIFFRACTION (2.1 Å)