ArticleBiochemistry2014
Analytical comparison of natural and pharmaceutical ventricular myosin activators.
Article in Biochemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
24 citing papers in PubMed, 34 citations in OpenAlex.
- Myosin Isoform-Dependent Effect of Omecamtiv Mecarbil on the Regulation of Force Generation in Human Cardiac Muscle.International journal of molecular sciences · 2024Article
- Omecamtiv Mecarbil in the treatment of heart failure: the past, the present, and the future.Frontiers in cardiovascular medicine · 2024Review
- Omecamtiv mecarbil augments cardiomyocyte contractile activity both at resting and systolic CaESC heart failure · 2023Article
- Insights into Muscle Contraction Derived from the Effects of Small-Molecular Actomyosin-Modulating Compounds.International journal of molecular sciences · 2022Article
- cMyBPC phosphorylation modulates the effect of omecamtiv mecarbil on myocardial force generation.The Journal of general physiology · 2021Article
- Single molecule turnover of fluorescent ATP by myosin and actomyosin unveil elusive enzymatic mechanisms.Communications biology · 2021Article
- Lost in translation: Interpreting cardiac muscle mechanics data in clinical practice.Archives of biochemistry and biophysics · 2019Review
- Do Actomyosin Single-Molecule Mechanics Data Predict Mechanics of Contracting Muscle?International journal of molecular sciences · 2018Review
- Single cardiac ventricular myosins are autonomous motors.Open biology · 2018Article
- Dose-Dependent Effects of the Myosin Activator Omecamtiv Mecarbil on Cross-Bridge Behavior and Force Generation in Failing Human Myocardium.Circulation. Heart failure · 2017Article
- Hypercontractile mutant of ventricular myosin essential light chain leads to disruption of sarcomeric structure and function and results in restrictive cardiomyopathy in mice.Cardiovascular research · 2017Article
- In vitro actin motility velocity varies linearly with the number of myosin impellers.Archives of biochemistry and biophysics · 2017Article
- Heart failure drug changes the mechanoenzymology of the cardiac myosin powerstroke.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Omecamtiv Mecarbil Enhances the Duty Ratio of Human β-Cardiac Myosin Resulting in Increased Calcium Sensitivity and Slowed Force Development in Cardiac Muscle.The Journal of biological chemistry · 2017Article
- In vivo myosin step-size from zebrafish skeletal muscle.Open biology · 2016Article
- Article
- Modulating Beta-Cardiac Myosin Function at the Molecular and Tissue Levels.Frontiers in physiology · 2016Article
- In vitro and in vivo single myosin step-sizes in striated muscle.Journal of muscle research and cell motility · 2015Article
- The novel cardiac myosin activator omecamtiv mecarbil increases the calcium sensitivity of force production in isolated cardiomyocytes and skeletal muscle fibres of the rat.British journal of pharmacology · 2015Article
- Structural basis for drug-induced allosteric changes to human β-cardiac myosin motor activity.Nature communications · 2015Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Ventricular myosin (βMys) is the motor protein in cardiac muscle generating force using ATP hydrolysis free energy to translate actin. In the cardiac muscle sarcomere, myosin and actin filaments interact cyclically and undergo rapid relative translation facilitated by the low duty cycle motor. It contrasts with high duty cycle processive myosins for which persistent actin association is the priority. The only pharmaceutical βMys activator, omecamtive mecarbil (OM), upregulates cardiac contractility in vivo and is undergoing testing for heart failure therapy. In vitro βMys step-size, motility velocity, and actin-activated myosin ATPase were measured to determine duty cycle in the absence and presence of OM. A new parameter, the relative step-frequency, was introduced and measured to characterize βMys motility due to the involvement of its three unitary step-sizes. Step-size and relative step-frequency were measured using the Qdot assay. OM decreases motility velocity 10-fold without affecting step-size, indicating a large increase in duty cycle converting βMys to a near processive myosin. The OM conversion dramatically increases force and modestly increases power over the native βMys. Contrasting motility modification due to OM with that from the natural myosin activator, specific βMys phosphorylation, provides insight into their respective activation mechanisms and indicates the boilerplate screening characteristics desired for pharmaceutical βMys activators. New analytics introduced here for the fast and efficient Qdot motility assay create a promising method for high-throughput screening of motor proteins and their modulators.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.