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5n6a

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Cardiac muscle myosin motor domain in the pre-powerstroke state

Structural highlights

5n6a is a 1 chain structure with sequence from Bos taurus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.1Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

MYH7_BOVIN Muscle contraction.

Publication Abstract from PubMed

Omecamtiv mecarbil is a selective, small-molecule activator of cardiac myosin that is being developed as a potential treatment for heart failure with reduced ejection fraction. Here we determine the crystal structure of cardiac myosin in the pre-powerstroke state, the most relevant state suggested by kinetic studies, both with (2.45 A) and without (3.10 A) omecamtiv mecarbil bound. Omecamtiv mecarbil does not change the motor mechanism nor does it influence myosin structure. Instead, omecamtiv mecarbil binds to an allosteric site that stabilizes the lever arm in a primed position resulting in accumulation of cardiac myosin in the primed state prior to onset of cardiac contraction, thus increasing the number of heads that can bind to the actin filament and undergo a powerstroke once the cardiac cycle starts. The mechanism of action of omecamtiv mecarbil also provides insights into uncovering how force is generated by molecular motors.Omecamtiv mecarbil (OM) is a cardiac myosin activator that is currently in clinical trials for heart failure treatment. Here, the authors give insights into its mode of action and present the crystal structure of OM bound to bovine cardiac myosin, which shows that OM stabilizes the pre-powerstroke state of myosin.

Mechanistic and structural basis for activation of cardiac myosin force production by omecamtiv mecarbil.,Planelles-Herrero VJ, Hartman JJ, Robert-Paganin J, Malik FI, Houdusse A Nat Commun. 2017 Aug 4;8(1):190. doi: 10.1038/s41467-017-00176-5. PMID:28775348^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Planelles-Herrero VJ, Hartman JJ, Robert-Paganin J, Malik FI, Houdusse A. Mechanistic and structural basis for activation of cardiac myosin force production by omecamtiv mecarbil. Nat Commun. 2017 Aug 4;8(1):190. doi: 10.1038/s41467-017-00176-5. PMID:28775348 doi:http://dx.doi.org/10.1038/s41467-017-00176-5

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5n6a"

@@ Line 3: / Line 3: @@
 <StructureSection load='5n6a' size='340' side='right'caption='[[5n6a]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5n6a]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5N6A OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5N6A FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5n6a]] 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=5N6A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5N6A FirstGlance]. <br>
-</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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.1&#8491;</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5n6a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n6a OCA], [http://pdbe.org/5n6a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5n6a RCSB], [http://www.ebi.ac.uk/pdbsum/5n6a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5n6a ProSAT]</span></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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=5n6a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n6a OCA], [https://pdbe.org/5n6a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5n6a RCSB], [https://www.ebi.ac.uk/pdbsum/5n6a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5n6a ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/MYH7_BOVIN MYH7_BOVIN]] Muscle contraction.
+[https://www.uniprot.org/uniprot/MYH7_BOVIN MYH7_BOVIN] Muscle contraction.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 27: / Line 28: @@
 [[Category: Bos taurus]]
 [[Category: Large Structures]]
-[[Category: Hartman, J J]]
+[[Category: Hartman JJ]]
-[[Category: Houdusse, A]]
+[[Category: Houdusse A]]
-[[Category: Malik, F I]]
+[[Category: Malik FI]]
-[[Category: Planelles-Herrero, V J]]
+[[Category: Planelles-Herrero VJ]]
-[[Category: Robert-Paganin, J]]
+[[Category: Robert-Paganin J]]
-[[Category: Cardiac]]
-[[Category: Motor protein]]
-[[Category: Myosin]]
-[[Category: Pre-powerstroke]]

5n6a

From Proteopedia

Current revision

Cardiac muscle myosin motor domain in the pre-powerstroke state

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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