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| == Function == | | == Function == |
| [https://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;">
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| == Publication Abstract from PubMed ==
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| 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.
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| 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>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 8qyp" style="background-color:#fffaf0;"></div>
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| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
