The primary focus of this laboratory is to understand the structure, function, and dynamics of cAMP-dependent Protein Kinase. This enzyme serves as a prototype for the entire protein kinase family. Functional sites and dynamic properties have been characterized by a variety of chemical, biophysical, and recombinant approaches. The role of phosphorylation and myristylation as well as local and global dynamics are being probed.

A crystal structure of the C-subunit, solved in 1991, was the first protein kinase structure solved. This structure provides the molecular framework for all protein kinase members. The folding of the polypeptide chain was revealed as well as the location of the conserved, residues throughout the core. Open and closed conformations provide an indication of the flexibility of the enzyme. Both ATP and the peptide binding are clearly delineated.

A structure with AlF3 provides a model for the transition state complex. Kinetic and fluorescent approaches are used to define individual steps associated with substrate binding and catalysis. The structure of the RIa and RIIb regulatory subunits have also been solved, and these reveal critical isoform specific differences.