The research plan involves examining the different families of calmodulin-dependent enzymes to determine: (1) structural or functional motifs (2) hydrophilicity/hydrophobicity index of putative calmodulin-binding regions; (3) the position of phosphorylation sites or pseudosubstrate domains or the homologous regions relative to the calmodulin-binding domain; (4) searching database for sequences similar to regions associated with calmodulin binding; (5) secondary structure prediction in the vicinity of the calmodulin (CAM) binding site; (6) internal repeated sequences via dot plot; (6) examination of local multiple alignments by dynamic programming procedures. Enzyme sequences to be investigated will include the entire spectrum of CAM target proteins. The spectrum includes: Class 1 target proteins that bind to CAM without associated Ca2+ and have little affinity for Ca2+-CAM; Class 2 proteins that bind CAM strongly in the absence of Ca2+ and are positively activated by Ca2+ ; and Class 3 proteins that have high affinity for the CAM-Ca2+ and weak or no affinity for Class 2 are macrophage NO synthases, lung cyclic 3', 5'-nucleotide phosphodiesterase, bordetella pertussis adenylate cyclase, and glycogen phosphorylase b kinase; and class 3 containing the remaining enzymes and proteins such as calcineurin, myosin light chain kinase, caldesmon, adenylate cyclases, fodrin, IP3 kinase, marcks protein, adducins, protein kinases, Ca2+ ATPase pumps and related proteins.
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