5drb: Difference between revisions

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== Function ==
== Function ==
[https://www.uniprot.org/uniprot/WNK1_RAT WNK1_RAT] Serine/threonine kinase which plays an important role in the regulation of electrolyte homeostasis, cell signaling, survival and proliferation. Acts as an activator and inhibitor of sodium-coupled chloride cotransporters and potassium-coupled chloride cotransporters respectively. Activates SCNN1A, SCNN1B, SCNN1D and SGK1. Controls sodium and chloride ion transport by inhibiting the activity of WNK4, by either phosphorylating the kinase or via an interaction between WNK4 and the autoinhibitory domain of WNK1. WNK4 regulates the activity of the thiazide-sensitive Na-Cl cotransporter, SLC12A3, by phosphorylation. WNK1 may also play a role in actin cytoskeletal reorganization. Phosphorylates NEDD4L.<ref>PMID:17975670</ref> <ref>PMID:20525693</ref>  
[https://www.uniprot.org/uniprot/WNK1_RAT WNK1_RAT] Serine/threonine kinase which plays an important role in the regulation of electrolyte homeostasis, cell signaling, survival and proliferation. Acts as an activator and inhibitor of sodium-coupled chloride cotransporters and potassium-coupled chloride cotransporters respectively. Activates SCNN1A, SCNN1B, SCNN1D and SGK1. Controls sodium and chloride ion transport by inhibiting the activity of WNK4, by either phosphorylating the kinase or via an interaction between WNK4 and the autoinhibitory domain of WNK1. WNK4 regulates the activity of the thiazide-sensitive Na-Cl cotransporter, SLC12A3, by phosphorylation. WNK1 may also play a role in actin cytoskeletal reorganization. Phosphorylates NEDD4L.<ref>PMID:17975670</ref> <ref>PMID:20525693</ref>  
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== Publication Abstract from PubMed ==
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.
Small-molecule WNK inhibition regulates cardiovascular and renal function.,Yamada K, Park HM, Rigel DF, DiPetrillo K, Whalen EJ, Anisowicz A, Beil M, Berstler J, Brocklehurst CE, Burdick DA, Caplan SL, Capparelli MP, Chen G, Chen W, Dale B, Deng L, Fu F, Hamamatsu N, Harasaki K, Herr T, Hoffmann P, Hu QY, Huang WJ, Idamakanti N, Imase H, Iwaki Y, Jain M, Jeyaseelan J, Kato M, Kaushik VK, 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 SJ, Raghavan S, Salem B, Shanado YH, Trakshel GM, Turner G, Wakai H, Wang C, Weldon S, Wielicki JB, Xie X, Xu L, Yagi YI, Yasoshima K, Yin J, Yowe D, Zhang JH, Zheng G, Monovich L Nat Chem Biol. 2016 Sep 5. doi: 10.1038/nchembio.2168. PMID:27595330<ref>PMID:27595330</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5drb" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==

Latest revision as of 15:25, 6 March 2024

Crystal structure of WNK1 in complex with WNK463Crystal structure of WNK1 in complex with WNK463

Structural highlights

5drb is a 1 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.65Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

WNK1_RAT Serine/threonine kinase which plays an important role in the regulation of electrolyte homeostasis, cell signaling, survival and proliferation. Acts as an activator and inhibitor of sodium-coupled chloride cotransporters and potassium-coupled chloride cotransporters respectively. Activates SCNN1A, SCNN1B, SCNN1D and SGK1. Controls sodium and chloride ion transport by inhibiting the activity of WNK4, by either phosphorylating the kinase or via an interaction between WNK4 and the autoinhibitory domain of WNK1. WNK4 regulates the activity of the thiazide-sensitive Na-Cl cotransporter, SLC12A3, by phosphorylation. WNK1 may also play a role in actin cytoskeletal reorganization. Phosphorylates NEDD4L.[1] [2]

See Also

References

  1. ↑ Yang CL, Zhu X, Ellison DH. The thiazide-sensitive Na-Cl cotransporter is regulated by a WNK kinase signaling complex. J Clin Invest. 2007 Nov;117(11):3403-11. PMID:17975670 doi:10.1172/JCI32033
  2. ↑ Heise CJ, Xu BE, Deaton SL, Cha SK, Cheng CJ, Earnest S, Sengupta S, Juang YC, Stippec S, Xu Y, Zhao Y, Huang CL, Cobb MH. Serum and glucocorticoid-induced kinase (SGK) 1 and the epithelial sodium channel are regulated by multiple with no lysine (WNK) family members. J Biol Chem. 2010 Aug 13;285(33):25161-7. doi: 10.1074/jbc.M110.103432. Epub 2010, Jun 4. PMID:20525693 doi:10.1074/jbc.M110.103432

5drb, resolution 1.65Å

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