8vpn
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Phosphorylated human NCC in complex with indapamide== | |
| + | <StructureSection load='8vpn' size='340' side='right'caption='[[8vpn]], [[Resolution|resolution]] 2.70Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8vpn]] 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=8VPN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8VPN 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]] 2.7Å</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=8vpn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8vpn OCA], [https://pdbe.org/8vpn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8vpn RCSB], [https://www.ebi.ac.uk/pdbsum/8vpn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8vpn 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. | ||
| - | + | 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> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 8vpn" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Cao EH]] | ||
| + | [[Category: Zhao YX]] | ||
Current revision
Phosphorylated human NCC in complex with indapamide
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