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6cn9

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Crystal structure of the Kinase domain of WNK1

Structural highlights

6cn9 is a 2 chain structure with sequence from Buffalo rat. This structure supersedes the now removed PDB entries 3fpq and 1t4h. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
NonStd Res:
Related:	3fpq
Gene:	Wnk1, Hsn2, Prkwnk1 (Buffalo rat)
Activity:	Non-specific serine/threonine protein kinase, with EC number 2.7.11.1
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]

Publication Abstract from PubMed

WNK kinases comprise a small group of unique serine/threonine protein kinases that have been genetically linked to pseudohypoaldosteronism type II, an autosomal dominant form of hypertension. Here we present the structure of the kinase domain of WNK1 at 1.8 A resolution, solved in a low activity conformation. A lysine residue (Lys-233) is found in the active site emanating from strand beta2 rather than strand beta3 as in other protein kinases. The activation loop adopts a unique well-folded inactive conformation. The conformations of the P+1 specificity pocket, the placement of the conserved active site threonine (Thr-386), and the exterior placement of helix C, contribute to the low activity state. By homology modeling, we identified two hydrophobic residues in the substrate-binding groove that contribute to substrate specificity. The structure of the WNK1 catalytic domain, with its unique active site, may help in the design of therapeutic reagents for the treatment of hypertension.

Crystal structure of the kinase domain of WNK1, a kinase that causes a hereditary form of hypertension.,Min X, Lee BH, Cobb MH, Goldsmith EJ Structure. 2004 Jul;12(7):1303-11. PMID:15242606^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ 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
↑ 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
↑ Min X, Lee BH, Cobb MH, Goldsmith EJ. Crystal structure of the kinase domain of WNK1, a kinase that causes a hereditary form of hypertension. Structure. 2004 Jul;12(7):1303-11. PMID:15242606 doi:http://dx.doi.org/10.1016/j.str.2004.04.014

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6cn9"

@@ Line 3: / Line 3: @@
 <StructureSection load='6cn9' size='340' side='right'caption='[[6cn9]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6cn9]] is a 2 chain structure. This structure supersedes the now removed PDB entries [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3fpq 3fpq] and [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1t4h 1t4h]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CN9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CN9 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6cn9]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. This structure supersedes the now removed PDB entries [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3fpq 3fpq] and [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1t4h 1t4h]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CN9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CN9 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3fpq|3fpq]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Wnk1, Hsn2, Prkwnk1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6cn9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cn9 OCA], [http://pdbe.org/6cn9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cn9 RCSB], [http://www.ebi.ac.uk/pdbsum/6cn9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cn9 ProSAT]</span></td></tr>
@@ Line 21: / Line 22: @@
 </div>
 <div class="pdbe-citations 6cn9" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Buffalo rat]]
 [[Category: Large Structures]]
 [[Category: Non-specific serine/threonine protein kinase]]

6cn9

From Proteopedia

Current revision

Crystal structure of the Kinase domain of WNK1

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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