5DRB

Crystal structure of WNK1 in complex with WNK463

Summary for 5DRB

• Entry DOI: 10.2210/pdb5drb/pdb
• Descriptor: 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)
• Functional Keywords: kinase, inhibitor, complex, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Rattus norvegicus (Rat)
• Cellular location: Cytoplasm : Q9JIH7
• Total number of polymer chains: 1
• Total formula weight: 34002.01

Authors

Kohls, D.,Xie, X. (deposition date: 2015-09-15, release date: 2016-09-07, Last modification date: 2024-03-06)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.65 Å)