A comparison has been made of the ability of seven calmodulin derivatives to displace 125I-labeled calmodulin and to activate adenylate cyclase in a brain particulate fraction. The activation of brain-soluble cyclic-nucleotide phosphodiesterase by the same calmodulin derivatives was examined in parallel. 2. In general, the dose for half-maximal inhibition of 125I-labeled calmodulin binding and the apparent Km of adenylate cyclase activation were comparable in brain membranes. These concentrations were 20--40-times higher than the corresponding apparent Km values of activation of cyclic-nucleotide phosphodiesterase. 3. Modifying the single histidine residue or both tyrosine residues exerted no influence on the biological properties of calmodulin. The carboxymethylation of two methionine residues or the amidation of several carboxyl groups reduced the activation properties of calmodulin on adenylate cyclase and cyclic-nucleotide phosphodiesterase. Altering seven lysine or four arginine residues resulted in two proteins whose activation properties on adenylate cyclase and phosphodiesterase had been modified in a way suggesting that lysine and arginine residues play distinct roles in the interaction of native calmodulin with each enzyme.
