CRITICAL AMINO-ACID-RESIDUES OF AIP, A HIGHLY SPECIFIC INHIBITORY PEPTIDE OF CALMODULIN-DEPENDENT PROTEIN-KINASE-II

The importance of the individual amino acid residues of AIP (KKALRRQEA VDAL), a highly specific inhibitor of calmodulin-dependent protein kin ase II (CaMKII), was studied, Replacement of Arg(6), Gln(7), or Ala(9) by other amino acid residues produced a marked increase in the IC50 v alue. Leu(4) and Val(10) were also sensitive to replacement, but some hydrophobic amino acids could substitute for these residues. Although replacement of Ala(3), Glu(8), Ala(12), and Leu(13) by other residues produced no significant increase in the IC50, the substitution of Lys for Ala(3) decreased the IC50. An AIP analog (KK (K) under bar LRRQEA (F) under bar DAY), in which Ala(3) and Val(10) were replaced with Lys and Phe, respectively, showed an IC50 value as low as 4 nM, suggestin g that it is a useful tool for studying the physiological roles of CaM KII. (C) 1998 Federation of European Biochemical Societies.