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==1.62A X-ray crystal structure of the conserved C-terminal (CCT) of human OSR1==
<StructureSection load='7okw' size='340' side='right'caption='[[7okw]], [[Resolution|resolution]] 1.62&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7okw]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7OKW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OKW FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.62&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7okw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7okw OCA], [https://pdbe.org/7okw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7okw RCSB], [https://www.ebi.ac.uk/pdbsum/7okw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7okw ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/OXSR1_HUMAN OXSR1_HUMAN] Regulates downstream kinases in response to environmental stress. May also have a function in regulating the actin cytoskeleton.<ref>PMID:14707132</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
STE20/SPS1-related proline/alanine-rich kinase (SPAK) and Oxidative Stress Responsive 1 (OSR1) kinase are two serine/threonine protein kinases that regulate the function of ion co-transporters through phosphorylation. The highly conserved C -terminal (CCT) domains of SPAK and OSR1 bind to RFx[V/I] peptide sequences from their upstream With No Lysine Kinases (WNKs), facilitating their activation via phosphorylation. Thus, the inhibition of SPAK and OSR1 binding, via their CCT domains, to WNK kinases is a plausible strategy for inhibiting SPAK and OSR1 kinases. To facilitate structure-guided drug design of such inhibitors, we expressed and purified human SPAK and OSR1 CCT domains and solved their crystal structures. Interestingly, these crystal structures show a highly conserved primary pocket adjacent to a flexible secondary pocket. We also employed a biophysical strategy and determined the affinity of SPAK and OSR1 CCT domains to short peptides derived from WNK4 and NKCC1. Together, this work provides a platform that facilitates the design of CCT domain specific small molecule binders that inhibit SPAK- and OSR1-activation by WNK kinases, and these could be useful in treating hypertension and ischemic stroke.

Structures of the Human SPAK and OSR1 Conserved C-Terminal (CCT) Domains.,Elvers KT, Lipka-Lloyd M, Trueman RC, Bax BD, Mehellou Y Chembiochem. 2021 Nov 2. doi: 10.1002/cbic.202100441. PMID:34726826<ref>PMID:34726826</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7okw" style="background-color:#fffaf0;"></div>

==See Also==
*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Bax BD]]
[[Category: Elvers KT]]
[[Category: Lipka-Lloyd M]]
[[Category: Mehellou Y]]