Protein Kinase A isoform dynamics and disease.

A number of disease mutations in the alpha and beta isoforms of Protein Kinase A have recently been identified. We model these mutations and investigate changes in conformational and protein/ligand interaction dynamics. Changes in partner protein and substrate interactions due to mutation is confirmed by fluorescence polarization binding and competition assays. Computational and biochemical approaches reveal a potential common mechanism among the mutations leading to kinase dysfunction.