What is the clinical evidence from this study?

Study design: Other. Population: Hypertrophic cardiomyopathy. Intervention: R453C mutation in human β-cardiac myosin. Primary outcome: Biochemical kinetic parameters (ATP binding and hydrolysis) (reduced by 35% (ATP binding); slowed 3-fold (ATP hydrolysis)).

What question did this study set out to answer?

This research examines how the R453C mutation in cardiac myosin affects ATP binding and hydrolysis, influencing hypertrophic cardiomyopathy severity.

December 17, 2013Journal of Biological ChemistryOpen Access

The Hypertrophic Cardiomyopathy Myosin Mutation R453C Alters ATP Binding and Hydrolysis of Human Cardiac β-Myosin

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Key result

The R453C mutation in human β-cardiac myosin reduced the rate constant for ATP binding by 35% and slowed the ATP hydrolysis step/recovery stroke 3-fold.

Population

Motor domain of human β-cardiac myosin carrying the R453C mutation

Comparison

R453C mutation vs Wild-type human β-cardiac myosin (implied)

Design

Preclinical

Authors

MBMarieke J. BloeminkCanterbury Christ Church University JDJohn C. DeaconWhitney Museum of American Art SLStephen J. LangerUniversity of North Carolina at Chapel Hill

Discussion

Member takes

Implication

R453C impairs myosin kinetics in HCM models; leaves open links to human phenotypes and therapies.

Key Points

This research examines how the R453C mutation in cardiac myosin affects ATP binding and hydrolysis, influencing hypertrophic cardiomyopathy severity.
Detailed biochemical kinetic analysis of the human β-cardiac myosin with R453C mutation.
Measurement of rate constants for ATP binding and hydrolysis steps.
Comparison with previous findings on the same mutation using optical traps.
ATP binding to the motor domain is reduced by 35%.
ATP hydrolysis and recovery stroke slowed 3-fold, indicating a potential rate-limiting step.
Minimal significant changes in other biochemical kinetic parameters despite mutation presence.

Structured PICO

Population

Motor domain of human β-cardiac myosin carrying the R453C mutation

Exposure

R453C mutation

Comparator

Wild-type human β-cardiac myosin (implied)

Outcome

Biochemical kinetic parameters (ATP binding and ATP hydrolysis step/recovery stroke)surrogate

Main Result

Effect estimate: reduced by 35% (ATP binding); slowed 3-fold (ATP hydrolysis)

The R453C mutation in human β-cardiac myosin, associated with severe hypertrophic cardiomyopathy, significantly impairs ATP binding and hydrolysis, likely by perturbing Switch-2 closure.

Cite This Study

Bloemink et al. (2013) studied Hypertrophic cardiomyopathy. R453C mutation in human β-cardiac myosin was evaluated on Biochemical kinetic parameters (ATP binding and hydrolysis) (reduced by 35% (ATP binding); slowed 3-fold (ATP hydrolysis)). The R453C mutation in human β-cardiac myosin reduced the rate constant for ATP binding by 35% and slowed the ATP hydrolysis step/recovery stroke 3-fold.

synapsesocial.com/papers/6a207ede55df6adc1bcd41a0 https://doi.org/10.1074/jbc.m113.511204

Topics

Hypertrophic cardiomyopathy

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The Hypertrophic Cardiomyopathy Myosin Mutation R453C Alters ATP Binding and Hydrolysis of Human Cardiac β-Myosin

Discussion

Member takes

Implication

Key Points

Structured PICO

Main Result

Cite This Study

Topics

The Hypertrophic Cardiomyopathy Myosin Mutation R453C Alters ATP Binding and Hydrolysis of Human Cardiac β-Myosin

Discussion

Member takes

Implication

Key Points

Structured PICO

Main Result

Cite This Study

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Topics

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