ArticleThe Journal of biological chemistry2014
The hypertrophic cardiomyopathy myosin mutation R453C alters ATP binding and hydrolysis of human cardiac β-myosin.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 60 citations in OpenAlex.
- Tonotopic specialization of MYO7A isoforms in auditory hair cells.Nature communications · 2026Article
- Unraveling Mutation-Induced Protein Communication Pathways in the Actomyosin Complex: Insights from Comprehensive Metadynamics Simulations.The journal of physical chemistry. B · 2025Article
- Mechanistic insights into effects of the cardiac myosin activator omecamtiv mecarbil from mechanokinetic modelling.Frontiers in physiology · 2025Article
- Obstructive hypertrophic cardiomyopathy: from genetic insights to a multimodal therapeutic approach with mavacamten, aficamten, and beyond.The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology · 2024Review
- MYH7 R453C induced cardiac remodelling via activating TGF-β/Smad2/3, ERK1/2 and Nox4/ROS/NF-κB signalling pathways.Open biology · 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
- Switch-2 determines MgFrontiers in physiology · 2024Article
- End-stage Hypertrophic Cardiomyopathy with Advanced Heart Failure in Patients Carrying MYH7 R453 Variants: A Case Series.Internal medicine (Tokyo, Japan) · 2023Article
- Cryo-EM structure of the folded-back state of human β-cardiac myosin.bioRxiv : the preprint server for biology · 2023Article
- Article
- Echocardiography and MALDI-TOF Identification of Myosin-Binding Protein C3 A74T Gene Mutations Involved Healthy and Mutated Bengal Cats.Animals : an open access journal from MDPI · 2022Article
- Critical Evaluation of Current Hypotheses for the Pathogenesis of Hypertrophic Cardiomyopathy.International journal of molecular sciences · 2022Review
- Genetic predisposition study of heart failure and its association with cardiomyopathy.The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology · 2022Review
- Hypertrophic cardiomyopathy: Mutations to mechanisms to therapies.Frontiers in physiology · 2022Review
- Investigation of the Recovery Stroke and ATP Hydrolysis and Changes Caused Due to the Cardiomyopathic Point Mutations in Human Cardiac β Myosin.The journal of physical chemistry. B · 2021Article
- A reverse stroke characterizes the force generation of cardiac myofilaments, leading to an understanding of heart function.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Molecular Genetic Basis of Hypertrophic Cardiomyopathy.Circulation research · 2021Article
- Stochastic allelic expression as trigger for contractile imbalance in hypertrophic cardiomyopathy.Biophysical reviews · 2020Review
- Myosin Sequestration Regulates Sarcomere Function, Cardiomyocyte Energetics, and Metabolism, Informing the Pathogenesis of Hypertrophic Cardiomyopathy.Circulation · 2020Article
- Myosin motor domains carrying mutations implicated in early or late onset hypertrophic cardiomyopathy have similar properties.The Journal of biological chemistry · 2019Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
The human hypertrophic cardiomyopathy mutation R453C results in one of the more severe forms of the myopathy. Arg-453 is found in a conserved surface loop of the upper 50-kDa domain of the myosin motor domain and lies between the nucleotide binding pocket and the actin binding site. It connects to the cardiomyopathy loop via a long α-helix, helix O, and to Switch-2 via the fifth strand of the central β-sheet. The mutation is, therefore, in a position to perturb a wide range of myosin molecular activities. We report here the first detailed biochemical kinetic analysis of the motor domain of the human β-cardiac myosin carrying the R453C mutation. A recent report of the same mutation (Sommese, R. F., Sung, J., Nag, S., Sutton, S., Deacon, J. C., Choe, E., Leinwand, L. A., Ruppel, K., and Spudich, J. A. (2013) Proc. Natl. Acad. Sci. U.S.A. 110, 12607-12612) found reduced ATPase and in vitro motility but increased force production using an optical trap. Surprisingly, our results show that the mutation alters few biochemical kinetic parameters significantly. The exceptions are the rate constants for ATP binding to the motor domain (reduced by 35%) and the ATP hydrolysis step/recovery stroke (slowed 3-fold), which could be the rate-limiting step for the ATPase cycle. Effects of the mutation on the recovery stroke are consistent with a perturbation of Switch-2 closure, which is required for the recovery stroke and the subsequent ATP hydrolysis.
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