... turnedinwards and interact with each other and with the a-helical linkers between the GAF A and B subdomains. In both structures, the cAMP-binding and cGMP-binding pockets are similar. A neighbouring ... GAF A and B bind cAMP (Fig. 1A,B,D,E). Again, the b1–b3region is the major interaction site for the adeninemoiety. In b1, an arginine residue (Ile417 in rPDE2)binds to N1 and a threonine (Ser419 ... Asp434 in rPDE2) that interacts with the pyrimidine ring of the purine, either individu-ally or in various combinations in 12 different con-structs, enhanced cAMP binding but had little effecton...