Critical amino acid residues of AIP, a highly specific inhibitory peptide of calmodulin‐dependent protein kinase II

FEBS Letters

Shigeri, Yasushi¹  Yumoto, Noboru¹  Fujisawa, Hitoshi²  Tatsu, Yoshiro¹  Uegaki, Koichi¹  Okuno, Sachiko²  Kameshita, Isamu²  Kitani, Takako²  Ishida, Atsuhiko² 

[1] Department of Organic Materials, Osaka National Research Institute, AIST, MITI, Midorigaoka, Ikeda, Osaka 563-0026, Japan;Department of Biochemistry, Asahikawa Medical College, Asahikawa 078-8510, Japan

关键词: Structure-function relationship;    Inhibitor;    Synthetic peptide;    Specificity;    Calmodulin-dependent protein kinase II;    CaMKII;    calmodulin-dependent protein kinase II;    CaMKIV;    calmodulin-dependent protein kinase IV;    PKA;    cyclic AMP-dependent protein kinase;    PKC;    protein kinase C;   

DOI  :  10.1016/S0014-5793(98)00405-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The importance of the individual amino acid residues of AIP (KKALRRQEAVDAL), a highly specific inhibitor of calmodulin-dependent protein kinase II (CaMKII), was studied. Replacement of Arg⁶, Gln⁷, or Ala⁹ by other amino acid residues produced a marked increase in the IC₅₀ value. Leu⁴ and Val¹⁰ were also sensitive to replacement, but some hydrophobic amino acids could substitute for these residues. Although replacement of Ala³, Glu⁸, Ala¹², and Leu¹³ by other residues produced no significant increase in the IC₅₀, the substitution of Lys for Ala³ decreased the IC₅₀. An AIP analog (KKLRRQEADAY), in which Ala³ and Val¹⁰ were replaced with Lys and Phe, respectively, showed an IC₅₀ value as low as 4 nM, suggesting that it is a useful tool for studying the physiological roles of CaMKII.

【 授权许可】

Unknown