REGULATORY SUBUNIT OF PROTEIN-KINASE-A - STRUCTURE OF DELETION MUTANTWITH CAMP BINDING DOMAINS

In the molecular scheme of living organisms, adenosine 3',5'-monophosp hate (cyclic AMP or cAMP) has been a universal second messenger. In eu karyotic cells, the primary receptors for cAMP are the regulatory subu nits of cAMP-dependent protein kinase. The crystal structure of a 1-91 deletion mutant of the type I alpha regulatory subunit was refined to 2.8 Angstrom resolution. Each of the two tandem cAMP binding domains provides an extensive network of hydrogen bonds that buries the cyclic phosphate and the ribose between two beta strands that are linked by a short alpha helix. Each adenine base stacks against an aromatic ring that lies outside the beta barrel. This structure provides a molecula r basis for understanding how cAMP binds cooperatively to its receptor protein, thus mediating activation of the kinase.