Towards the full molecular investigation of protein kinase a mediated catalysis by NMR spectroscopy.

The reversible phosphorylation of proteins is fundamental to the modulation of myocardial contraction. A mechanism which controls this modulation occurs through alterations of Ca2+ flux formed across the sarcoplasmic reticulum (SR) membrane inside cardiomyocytes. Changes in this flux have a profound dependence on the interactions of three proteins: protein kinase A (PKA), sarcoendoplasmic reticulum Ca2+-ATPase (SERCA), and phospholamban (PLN). Phosphorylation of PLN by PKA is associated with an augmented rate of SR Ca2+ uptake and relaxation of the myocardium. Mutants of PLN (R9C-PLN and R14Del-PLN) have previously been shown to be linked with forms of the fatal hereditary disease, dilated cardiomyopathy. The molecular basis of disease in this situation could result from irregularities in the association of these PLN mutants with PKA. The work presented here lays the foundation for obtaining the molecular details which govern these interactions to further our understanding of the processes which control Ca2+ transport in myocytes and, perhaps, lend insight into the origins of this disease.

Author dc:creator

• Masterson, Larry Raou

• Allostery
• Cooperativity
• Nuclear Magnetic Resonance
• Protein Kinase
• Chemistry

Language dc:language.iso

en_US

Repository record dc:identifier.uri

http://purl.umn.edu/49899

OAI identifier oai:identifier

oai:conservancy.umn.edu:11299/49899