5DRB

Crystal structure of WNK1 in complex with WNK463

5DRB の概要

• エントリーDOI: 10.2210/pdb5drb/pdb
• 分子名称: Serine/threonine-protein kinase WNK1, N-tert-butyl-1-(1-{5-[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl]pyridin-2-yl}piperidin-4-yl)-1H-imidazole-5-carboxamide (3 entities in total)
• 機能のキーワード: kinase, inhibitor, complex, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Rattus norvegicus (Rat)
• 細胞内の位置: Cytoplasm : Q9JIH7
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 34002.01

構造登録者

Kohls, D.,Xie, X. (登録日: 2015-09-15, 公開日: 2016-09-07, 最終更新日: 2024-03-06)

主引用文献

Yamada, K.,Park, H.M.,Rigel, D.F.,DiPetrillo, K.,Whalen, E.J.,Anisowicz, A.,Beil, M.,Berstler, J.,Brocklehurst, C.E.,Burdick, D.A.,Caplan, S.L.,Capparelli, M.P.,Chen, G.,Chen, W.,Dale, B.,Deng, L.,Fu, F.,Hamamatsu, N.,Harasaki, K.,Herr, T.,Hoffmann, P.,Hu, Q.Y.,Huang, W.J.,Idamakanti, N.,Imase, H.,Iwaki, Y.,Jain, M.,Jeyaseelan, J.,Kato, M.,Kaushik, V.K.,Kohls, D.,Kunjathoor, V.,LaSala, D.,Lee, J.,Liu, J.,Luo, Y.,Ma, F.,Mo, R.,Mowbray, S.,Mogi, M.,Ossola, F.,Pandey, P.,Patel, S.J.,Raghavan, S.,Salem, B.,Shanado, Y.H.,Trakshel, G.M.,Turner, G.,Wakai, H.,Wang, C.,Weldon, S.,Wielicki, J.B.,Xie, X.,Xu, L.,Yagi, Y.I.,Yasoshima, K.,Yin, J.,Yowe, D.,Zhang, J.H.,Zheng, G.,Monovich, L.
Small-molecule WNK inhibition regulates cardiovascular and renal function.
Nat.Chem.Biol., 12:896-898, 2016

PubMed Abstract: The With-No-Lysine (K) (WNK) kinases play a critical role in blood pressure regulation and body fluid and electrolyte homeostasis. Herein, we introduce the first orally bioavailable pan-WNK-kinase inhibitor, WNK463, that exploits unique structural features of the WNK kinases for both affinity and kinase selectivity. In rodent models of hypertension, WNK463 affects blood pressure and body fluid and electro-lyte homeostasis, consistent with WNK-kinase-associated physiology and pathophysiology.

PubMed: 27595330
DOI: 10.1038/nchembio.2168

実験手法

X-RAY DIFFRACTION (1.65 Å)