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Inhibition of calcium-calmodulin complex formation by vasorelaxant basic dipeptides demonstrated by in vitro and in silico analyses.
Kumrungsee, Thanutchaporn; Saiki, Tomomi; Akiyama, Sayaka; Nakashima, Kentaro; Tanaka, Mitsuru; Kobayashi, Yutaro; Matsui, Toshiro.
Afiliação
  • Kumrungsee T; Faculty of Agriculture, Graduate School of Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan.
  • Saiki T; Faculty of Agriculture, Graduate School of Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan.
  • Akiyama S; Faculty of Agriculture, Graduate School of Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan.
  • Nakashima K; Faculty of Agriculture, Graduate School of Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan.
  • Tanaka M; Faculty of Agriculture, Graduate School of Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan.
  • Kobayashi Y; Faculty of Agriculture, Graduate School of Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan.
  • Matsui T; Faculty of Agriculture, Graduate School of Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan. Electronic address: tmatsui@agr.kyushu-u.ac.jp.
Biochim Biophys Acta ; 1840(10): 3073-8, 2014 Oct.
Article em En | MEDLINE | ID: mdl-25092650
BACKGROUND: Tryptophan-histidine (Trp-His) was found to suppress the activity of the Ca²âº/calmodulin (CaM)-dependent protein kinases II (CaMKII), which requires the Ca²âº-CaM complex for an initial activation. In this study, we attempted to clarify whether Trp-His inhibits Ca²âº-CaM complex formation, a CaMKII activator. METHODS: The ability of Trp-His and other peptides to inhibit Ca²âº-CaM complex formation was investigated by a Ca²âº-encapsulation fluorescence assay. The peptide-CaM interactions were illustrated by molecular dynamic simulation. RESULTS: We showed that Trp-His inhibited Ca²âº-CaM complex formation with a 1:1 binding stoichiometry of the peptide to CaM, considering that Trp-His reduced Hill coefficient of Ca²âº-CaM binding from 2.81 to 1.92. His-Trp also showed inhibitory activity, whereas Trp+His, 3-methyl His-Trp, and Phe-His did not show significant inhibitory activity, suggesting that the inhibitory activity was due to a peptide skeleton (irrespective of the sequence), a basic amino acid, a His residue, the N hydrogen atom of its imidazole ring, and Trp residue. In silico studies suggested the possibility that Trp-His and His-Trp interacted with the Ca²âº-binding site of CaM by forming hydrogen bonds with key Ca²âº-binding residues of CaM, with a binding free energy of -49.1 and -68.0 kJ/mol, respectively. CONCLUSIONS: This is the first study demonstrating that the vasoactive dipeptide Trp-His possesses inhibitory activity against Ca²âº-CaM complex formation, which may elucidate how Trp-His inhibited CaMKII in a previous study. GENERAL SIGNIFICANCE: The results provide a basic idea that could lead to the development of small peptides binding with high affinity to CaM and inhibiting Ca²âº-CaM complex formation in the future.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vasodilatadores / Calmodulina / Cálcio / Dipeptídeos Limite: Animals Idioma: En Ano de publicação: 2014 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vasodilatadores / Calmodulina / Cálcio / Dipeptídeos Limite: Animals Idioma: En Ano de publicação: 2014 Tipo de documento: Article