|
|
| Line 1: |
Line 1: |
| - | | + | #REDIRECT [[6cn9]] This PDB entry is obsolete and replaced by 6cn9 |
| - | ==Crystal structure of the kinase domain of WNK1==
| + | |
| - | <StructureSection load='3fpq' size='340' side='right' caption='[[3fpq]], [[Resolution|resolution]] 1.80Å' scene=''>
| + | |
| - | == Structural highlights ==
| + | |
| - | <table><tr><td colspan='2'>[[3fpq]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. This structure supersedes the now removed PDB entry [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=3FPQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3FPQ 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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Prkwnk1, Wnk1 ([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=3fpq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fpq OCA], [http://pdbe.org/3fpq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3fpq RCSB], [http://www.ebi.ac.uk/pdbsum/3fpq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3fpq ProSAT]</span></td></tr>
| + | |
| - | </table>
| + | |
| - | == Function ==
| + | |
| - | [[http://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>
| + | |
| - | == Evolutionary Conservation ==
| + | |
| - | [[Image:Consurf_key_small.gif|200px|right]]
| + | |
| - | Check<jmol>
| + | |
| - | <jmolCheckbox>
| + | |
| - | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fp/3fpq_consurf.spt"</scriptWhenChecked>
| + | |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
| + | |
| - | <text>to colour the structure by Evolutionary Conservation</text>
| + | |
| - | </jmolCheckbox>
| + | |
| - | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3fpq ConSurf].
| + | |
| - | <div style="clear:both"></div>
| + | |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == 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<ref>PMID:15242606</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 3fpq" style="background-color:#fffaf0;"></div>
| + | |
| - | | + | |
| - | ==See Also==
| + | |
| - | *[[Serine/threonine protein kinase|Serine/threonine protein kinase]]
| + | |
| - | == References ==
| + | |
| - | <references/>
| + | |
| - | __TOC__
| + | |
| - | </StructureSection>
| + | |
| - | [[Category: Buffalo rat]]
| + | |
| - | [[Category: Non-specific serine/threonine protein kinase]]
| + | |
| - | [[Category: Cobb, M H]]
| + | |
| - | [[Category: Goldsmith, E J]]
| + | |
| - | [[Category: Lee, B H]]
| + | |
| - | [[Category: Min, X]]
| + | |
| - | [[Category: Atp-binding]]
| + | |
| - | [[Category: Kinase]]
| + | |
| - | [[Category: Nucleotide-binding]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Protein kinase inhibitor]]
| + | |
| - | [[Category: Protein serine/threonine kinase]]
| + | |
| - | [[Category: Serine/threonine-protein kinase]]
| + | |
| - | [[Category: Transferase]]
| + | |
| - | [[Category: Wnk1]]
| + | |
