Structural basis for drug-induced allosteric changes to human β-cardiac myosin motor activity

@inproceedings{Winkelmann2015StructuralBF,
  title={Structural basis for drug-induced allosteric changes to human β-cardiac myosin motor activity},
  author={Donald A. Winkelmann and Eva Forgacs and Matthew Thomas Miller and Ann M Stock},
  booktitle={Nature communications},
  year={2015}
}
Omecamtiv Mecarbil (OM) is a small molecule allosteric effector of cardiac myosin that is in clinical trials for treatment of systolic heart failure. A detailed kinetic analysis of cardiac myosin has shown that the drug accelerates phosphate release by shifting the equilibrium of the hydrolysis step towards products, leading to a faster transition from weak to strong actin-bound states. The structure of the human β-cardiac motor domain (cMD) with OM bound reveals a single OM-binding site… CONTINUE READING

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Cardiac human myosin S1dc, beta isofrom complexed with Mn-AMPPNP

  • V. Klenchin, J. Deacon, A. Combs, L. Leinwand, I. Rayment
  • PDB ID:
  • 2012

Structure of the rigor actin-tropomyosin-myosin complex

  • E Behrmann
  • Cell 150,
  • 2012

a potential therapeutic approach for systolic heart failure

  • Malik, F. I. et al. Cardiac myosin activation
  • Science 331, 1439-43
  • 2011

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