OCA at 11:47, 13 December 2023

OCA — Wed, 13 Dec 2023 11:47:28 GMT

←Older revision		Revision as of 11:47, 13 December 2023
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 8qyp is ~~ON HOLD until Paper~~ Publication	+	==Beta-cardiac myosin motor domain in the pre-powerstroke state==
		+	<StructureSection load='8qyp' size='340' side='right'caption='[[8qyp]], [[Resolution\|resolution]] 2.76Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8qyp]] 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=8QYP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8QYP 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]] 2.759Å</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=M3L:N-TRIMETHYLLYSINE'>M3L</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=VO4:VANADATE+ION'>VO4</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=8qyp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8qyp OCA], [https://pdbe.org/8qyp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8qyp RCSB], [https://www.ebi.ac.uk/pdbsum/8qyp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8qyp 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~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: ~~David, A~~]]	+	<div class="pdbe-citations 8qyp" 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]]

OCA at 06:35, 29 November 2023

OCA — Wed, 29 Nov 2023 06:35:02 GMT

←Older revision		Revision as of 06:35, 29 November 2023
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8qyp is ON HOLD	+	The entry 8qyp is ON HOLD until Paper Publication

	Authors: Robert-Paganin, J., Kikuti, C., Auguin, D., Rety, S., David, A., Houdusse, A.		Authors: Robert-Paganin, J., Kikuti, C., Auguin, D., Rety, S., David, A., Houdusse, A.

OCA: Protected "8qyp" [edit=sysop:move=sysop]

OCA — Wed, 01 Nov 2023 10:45:06 GMT

Protected "8qyp" [edit=sysop:move=sysop]

←Older revision

Revision as of 10:45, 1 November 2023

OCA: New page: '''Unreleased structure''' The entry 8qyp is ON HOLD Authors: Robert-Paganin, J., Kikuti, C., Auguin, D., Rety, S., David, A., Houdusse, A. Description: Beta-cardiac myosin motor domai...

OCA — Wed, 01 Nov 2023 10:44:59 GMT

New page: '''Unreleased structure''' The entry 8qyp is ON HOLD Authors: Robert-Paganin, J., Kikuti, C., Auguin, D., Rety, S., David, A., Houdusse, A. Description: Beta-cardiac myosin motor domai...

New page

'''Unreleased structure'''

The entry 8qyp is ON HOLD

Authors: Robert-Paganin, J., Kikuti, C., Auguin, D., Rety, S., David, A., Houdusse, A.

Description: Beta-cardiac myosin motor domain in the pre-powerstroke state
[[Category: Unreleased Structures]]
[[Category: David, A]]
[[Category: Auguin, D]]
[[Category: Kikuti, C]]
[[Category: Rety, S]]
[[Category: Houdusse, A]]
[[Category: Robert-Paganin, J]]

8qyp - Revision history

OCA at 11:47, 13 December 2023

OCA at 06:35, 29 November 2023

OCA: Protected "8qyp" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 8qyp is ON HOLD Authors: Robert-Paganin, J., Kikuti, C., Auguin, D., Rety, S., David, A., Houdusse, A. Description: Beta-cardiac myosin motor domai...