ArticleeLife2021
Myosin with hypertrophic cardiac mutation R712L has a decreased working stroke which is rescued by omecamtiv mecarbil.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 52 citations in OpenAlex.
- Mavacamten inhibits myosin activity by stabilizing the myosin interacting-heads motif and stalling motor force generation.Science advances · 2026Article
- A myosin hypertrophic cardiomyopathy mutation disrupts the super-relaxed state and boosts contractility by enhanced actin attachment.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- S2Tag, a novel affinity tag for the capture and immobilization of coiled-coil proteins: Application to the study of human β-cardiac myosin.The Journal of biological chemistry · 2025Article
- Hypertrophic cardiomyopathy mutations Y115H and E497D disrupt the folded-back state of human β-cardiac myosin allosterically.Nature communications · 2025Article
- Delayed phosphate release can highly improve energy efficiency of muscle contraction.Biophysical journal · 2025Article
- Dynamics of β-cardiac myosin between the super-relaxed and disordered-relaxed states.The Journal of biological chemistry · 2025Article
- A computational framework for identifying cytoskeletal genes associated with age-related diseases.Scientific reports · 2025Article
- Probing actin-activated ATP turnover kinetics of human cardiac myosin II by single molecule fluorescence.Cytoskeleton (Hoboken, N.J.) · 2024Article
- Pharmacodynamics of single-dose omecamtiv mecarbil administered intravenously in clinically healthy cats.Open veterinary journal · 2024Article
- Dynamics of the Pre-Powerstroke Myosin Lever Arm and the Effects of Omecamtiv Mecarbil.International journal of molecular sciences · 2024Article
- Human cardiac β-myosin powerstroke energetics: Thin filament, Pi displacement, and mutation effects.Biophysical journal · 2024Article
- Dilated cardiomyopathy mutation in beta-cardiac myosin enhances actin activation of the power stroke and phosphate release.PNAS nexus · 2024Article
- Cost-Efficient Expression of Human Cardiac Myosin Heavy Chain in C2C12 Cells with a Non-Viral Transfection Reagent.International journal of molecular sciences · 2024Article
- Omecamtiv mecarbil and Mavacamten target the same myosin pocket despite opposite effects in heart contraction.Nature communications · 2024Article
- Myosin-Catalyzed ATP Hydrolysis in the Presence of Disease-Causing Mutations: Mavacamten as a Way to Repair Mechanism.The journal of physical chemistry. B · 2024Article
- Modeling thick filament activation suggests a molecular basis for force depression.Biophysical journal · 2024Article
- Assessing Cardiac Contractility From Single Molecules to Whole Hearts.JACC. Basic to translational science · 2024Review
- Homologous mutations in human β, embryonic, and perinatal muscle myosins have divergent effects on molecular power generation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Motility Assay to Probe the Calcium Sensitivity of Myosin and Regulated Thin Filaments.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Omecamtiv Mecarbil in the treatment of heart failure: the past, the present, and the future.Frontiers in cardiovascular medicine · 2024Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Hypertrophic cardiomyopathies (HCMs) are the leading cause of acute cardiac failure in young individuals. Over 300 mutations throughout β-cardiac myosin, including in the motor domain, are associated with HCM. A β-cardiac myosin motor mutation (R712L) leads to a severe form of HCM. Actin-gliding motility of R712L-myosin is inhibited, despite near-normal ATPase kinetics. By optical trapping, the working stroke of R712L-myosin was decreased 4-fold, but actin-attachment durations were normal. A prevalent hypothesis that HCM mutants are hypercontractile is thus not universal. R712 is adjacent to the binding site of the heart failure drug omecamtiv mecarbil (OM). OM suppresses the working stroke of normal β-cardiac myosin, but remarkably, OM rescues the R712L-myosin working stroke. Using a flow chamber to interrogate a single molecule during buffer exchange, we found OM rescue to be reversible. Thus, the R712L mutation uncouples lever arm rotation from ATPase activity and this inhibition is rescued by OM.
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