In the molecular scheme of living organisms, adenosine 3'-5' monophosphate (cyclic AMP or cAMP) has been a universal second messenger. In eukaryotic cells, the primary receptor for cAMP are regulatory subunits of cAMP-dependent protein kinase. The crystal structure of a 1-91 deletion mutant of the type Ia regulatory subunit was refined to 2.8 E resolution using data from 7-1 beam line of SSRL. Each of the two tandem cAMP binding domains provides an extensive network of hydrogen bonds that buries the cyclic phosphate and the ribose between the two _ -strands that are linked by a short ?-helix. Each adenine base stacks against an aromatic ring that lies outside the _-barrel. This structure provides a molecular basis of understanding how cAMP binds cooperatively to its receptor protein, thus mediating activation of the kinase. Since the determination of the deletion mutant structure, crystals of the wild-type Ia regulatory dimer have been obtained. A low resolution 4.5 E data set from these crystals was collected in the laboratory source. We have yet to succeed in our attempts to get better data from the synchrotron source.
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