8vpp: Difference between revisions

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'''Unreleased structure'''


The entry 8vpp is ON HOLD  until Paper Publication
==Phosphorylated human NCC in complex with chlorthalidone==
<StructureSection load='8vpp' size='340' side='right'caption='[[8vpp]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8vpp]] 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=8VPP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8VPP FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.9&#8491;</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=8vpp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8vpp OCA], [https://pdbe.org/8vpp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8vpp RCSB], [https://www.ebi.ac.uk/pdbsum/8vpp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8vpp ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/J3QSS1_HUMAN J3QSS1_HUMAN]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The Na(+)-Cl(-) cotransporter (NCC) drives salt reabsorption in the kidney and plays a decisive role in balancing electrolytes and blood pressure. Thiazide and thiazide-like diuretics inhibit NCC-mediated renal salt retention and have been cornerstones for treating hypertension and edema since the 1950s. Here we determine NCC co-structures individually complexed with the thiazide drug hydrochlorothiazide, and two thiazide-like drugs chlorthalidone and indapamide, revealing that they fit into an orthosteric site and occlude the NCC ion translocation pathway. Aberrant NCC activation by the WNKs-SPAK kinase cascade underlies Familial Hyperkalemic Hypertension, but it remains unknown whether/how phosphorylation transforms the NCC structure to accelerate ion translocation. We show that an intracellular amino-terminal motif of NCC, once phosphorylated, associates with the carboxyl-terminal domain, and together, they interact with the transmembrane domain. These interactions suggest a phosphorylation-dependent allosteric network that directly influences NCC ion translocation.


Authors:  
Structural bases for Na(+)-Cl(-) cotransporter inhibition by thiazide diuretic drugs and activation by kinases.,Zhao Y, Schubert H, Blakely A, Forbush B, Smith MD, Rinehart J, Cao E Nat Commun. 2024 Aug 14;15(1):7006. doi: 10.1038/s41467-024-51381-y. PMID:39143061<ref>PMID:39143061</ref>


Description:  
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
<div class="pdbe-citations 8vpp" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Cao EH]]
[[Category: Zhao YX]]
Retrieved from "https://proteopedia.org/8vpp"