7o86: Difference between revisions
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==1.73A X-ray crystal structure of the conserved C-terminal (CCT) of human SPAK== | ==1.73A X-ray crystal structure of the conserved C-terminal (CCT) of human SPAK== | ||
<StructureSection load='7o86' size='340' side='right'caption='[[7o86]]' scene=''> | <StructureSection load='7o86' size='340' side='right'caption='[[7o86]], [[Resolution|resolution]] 1.73Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7O86 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7O86 FirstGlance]. <br> | <table><tr><td colspan='2'>[[7o86]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7O86 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7O86 FirstGlance]. <br> | ||
</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=7o86 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7o86 OCA], [https://pdbe.org/7o86 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7o86 RCSB], [https://www.ebi.ac.uk/pdbsum/7o86 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7o86 ProSAT]</span></td></tr> | </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=NA:SODIUM+ION'>NA</scene></td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=7o86 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7o86 OCA], [https://pdbe.org/7o86 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7o86 RCSB], [https://www.ebi.ac.uk/pdbsum/7o86 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7o86 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[[https://www.uniprot.org/uniprot/STK39_HUMAN STK39_HUMAN]] May act as a mediator of stress-activated signals. Mediates the inhibition of SLC4A4, SLC26A6 as well as CFTR activities by the WNK scaffolds, probably through phosphorylation. Phosphorylates RELT.[UniProtKB:Q9Z1W9] | |||
<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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7o86" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Bax | [[Category: Non-specific serine/threonine protein kinase]] | ||
[[Category: Elvers | [[Category: Bax, B D]] | ||
[[Category: Lipka-Lloyd M]] | [[Category: Elvers, K T]] | ||
[[Category: Mehellou Y]] | [[Category: Lipka-Lloyd, M]] | ||
[[Category: Mehellou, Y]] | |||
[[Category: Cct]] | |||
[[Category: Kinase]] | |||
[[Category: Signaling protein]] | |||
[[Category: Transferase]] | |||