8qyr: Difference between revisions

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-'''Unreleased structure'''
-The entry 8qyr is ON HOLD
+==Beta-cardiac myosin motor domain in the pre-powerstroke state complexed to Mavacamten==
+<StructureSection load='8qyr' size='340' side='right'caption='[[8qyr]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8qyr]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8QYR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8QYR 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]] 1.8&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=BEF:BERYLLIUM+TRIFLUORIDE+ION'>BEF</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=M3L:N-TRIMETHYLLYSINE'>M3L</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=XB2:6-[[(1~{S})-1-phenylethyl]amino]-3-propan-2-yl-1~{H}-pyrimidine-2,4-dione'>XB2</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=8qyr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8qyr OCA], [https://pdbe.org/8qyr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8qyr RCSB], [https://www.ebi.ac.uk/pdbsum/8qyr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8qyr ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/MYH7_BOVIN MYH7_BOVIN] Muscle contraction.
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Inherited cardiomyopathies are amongst the most common cardiac diseases worldwide, leading in the late-stage to heart failure and death. The most promising treatments against these diseases are small-molecules directly modulating the force produced by beta-cardiac myosin, the molecular motor driving heart contraction. Two of these molecules that produce antagonistic effects on cardiac contractility have completed clinical phase 3 trials: the activator Omecamtiv mecarbil and the inhibitor Mavacamten. In this work, we reveal by X-ray crystallography that both drugs target the same pocket and stabilize a pre-stroke structural state, with only few local differences. All atoms molecular dynamics simulations reveal how these molecules can have antagonistic impact on the allostery of the motor by comparing beta-cardiac myosin in the apo form or bound to Omecamtiv mecarbil or Mavacamten. Altogether, our results provide the framework for rational drug development for the purpose of personalized medicine.
-Authors: Robert-Paganin, J., Kikuti, C., Auguin, D., Rety, S., David, A., Houdusse, A.
+Omecamtiv mecarbil and Mavacamten target the same myosin pocket despite antagonistic effects in heart contraction.,Auguin D, Robert-Paganin J, Rety S, Kikuti C, David A, Theumer G, Schmidt AW, Knolker HJ, Houdusse A bioRxiv. 2023 Nov 15:2023.11.15.567213. doi: 10.1101/2023.11.15.567213. Preprint. PMID:38014327<ref>PMID:38014327</ref>
-Description: Beta-cardiac myosin motor domain in the pre-powerstroke state complexed to Mavacamten
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: David, A]]
+<div class="pdbe-citations 8qyr" style="background-color:#fffaf0;"></div>
-[[Category: Auguin, D]]
+== References ==
-[[Category: Kikuti, C]]
+<references/>
-[[Category: Rety, S]]
+__TOC__
-[[Category: Houdusse, A]]
+</StructureSection>
-[[Category: Robert-Paganin, J]]
+[[Category: Bos taurus]]
+[[Category: Large Structures]]
+[[Category: Auguin D]]
+[[Category: David A]]
+[[Category: Houdusse A]]
+[[Category: Kikuti C]]
+[[Category: Rety S]]
+[[Category: Robert-Paganin J]]