8uxe
From Proteopedia
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(New page: '''Unreleased structure''' The entry 8uxe is ON HOLD Authors: Miotto, M.C., Marks, A.R. Description: Structure of PKA phosphorylated human RyR2-R420Q in the closed state in the presenc...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Structure of PKA phosphorylated human RyR2-R420Q in the closed state in the presence of ARM210== | |
| + | <StructureSection load='8uxe' size='340' side='right'caption='[[8uxe]], [[Resolution|resolution]] 3.53Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8uxe]] is a 8 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=8UXE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8UXE 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]] 3.53Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=KVR:4-[(7-methoxy-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)methyl]benzoic+acid'>KVR</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=8uxe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8uxe OCA], [https://pdbe.org/8uxe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8uxe RCSB], [https://www.ebi.ac.uk/pdbsum/8uxe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8uxe ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/FKB1B_HUMAN FKB1B_HUMAN] Has the potential to contribute to the immunosuppressive and toxic effects of FK506 and rapamycin. PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Heart failure, the leading cause of mortality and morbidity in the developed world, is characterized by cardiac ryanodine receptor 2 channels that are hyperphosphorylated, oxidized, and depleted of the stabilizing subunit calstabin-2. This results in a diastolic sarcoplasmic reticulum Ca(2+) leak that impairs cardiac contractility and triggers arrhythmias. Genetic mutations in ryanodine receptor 2 can also cause Ca(2+) leak, leading to arrhythmias and sudden cardiac death. Here, we solved the cryogenic electron microscopy structures of ryanodine receptor 2 variants linked either to heart failure or inherited sudden cardiac death. All are in the primed state, part way between closed and open. Binding of Rycal drugs to ryanodine receptor 2 channels reverts the primed state back towards the closed state, decreasing Ca(2+) leak, improving cardiac function, and preventing arrhythmias. We propose a structural-physiological mechanism whereby the ryanodine receptor 2 channel primed state underlies the arrhythmias in heart failure and arrhythmogenic disorders. | ||
| - | + | Structural basis for ryanodine receptor type 2 leak in heart failure and arrhythmogenic disorders.,Miotto MC, Reiken S, Wronska A, Yuan Q, Dridi H, Liu Y, Weninger G, Tchagou C, Marks AR Nat Commun. 2024 Sep 15;15(1):8080. doi: 10.1038/s41467-024-51791-y. PMID:39278969<ref>PMID:39278969</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 8uxe" style="background-color:#fffaf0;"></div> |
| - | [[Category: Marks | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Marks AR]] | ||
| + | [[Category: Miotto MC]] | ||
Current revision
Structure of PKA phosphorylated human RyR2-R420Q in the closed state in the presence of ARM210
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