Inhibition of calcium-calmodulin complex formation by vasorelaxant basic dipeptides demonstrated by in vitro and in silico analyses.
Inhibition of calcium-calmodulin complex formation by vasorelaxant basic dipeptides demonstrated by in vitro and in silico analyses.
复制标题
体外和计算机分析证明血管舒张碱性二肽对钙-钙调蛋白复合物形成的抑制。
DOI：
10.1016/j.bbagen.2014.07.020
复制
发表时间：
2014
期刊：
影响因子：
--
通讯作者：
T. Matsui
中科院分区：
文献类型：
--
作者：
Thanutchaporn Kumrungsee;Tomomi Saiki;Sayaka Akiyama;K. Nakashima;Mitsuru Tanaka;Yutaro Kobayashi;T. Matsui
BackgroundTryptophan-histidine (Trp-His) was found to suppress the activity of the Ca2 +/calmodulin (CaM)-dependent protein kinases II (CaMKII), which requires the Ca2 +-CaM complex for an initial activation. In this study, we attempted to clarify whether Trp-His inhibits Ca2 +-CaM complex formation, a CaMKII activator.MethodsThe ability of Trp-His and other peptides to inhibit Ca2 +-CaM complex formation was investigated by a Ca2 +-encapsulation fluorescence assay. The peptide-CaM interactions were illustrated by molecular dynamic simulation.ResultsWe showed that Trp-His inhibited Ca2 +-CaM complex formation with a 1:1 binding stoichiometry of the peptide to CaM, considering that Trp-His reduced Hill coefficient of Ca2 +-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 silicostudies suggested the possibility that Trp-His and His-Trp interacted with the Ca2 +-binding site of CaM by forming hydrogen bonds with key Ca2 +-binding residues of CaM, with a binding free energy of − 49.1 and − 68.0 kJ/mol, respectively.ConclusionsThis is the first study demonstrating that the vasoactive dipeptide Trp-His possesses inhibitory activity against Ca2 +-CaM complex formation, which may elucidate how Trp-His inhibited CaMKII in a previous study.General significanceThe results provide a basic idea that could lead to the development of small peptides binding with high affinity to CaM and inhibiting Ca2 +-CaM complex formation in the future.
影响因子：
3
作者：
Christel, Carl;Lee, Amy
通讯作者：
Lee, Amy
钙调蛋白与羰花青染料 (Stains-all) 的相互作用。
DOI：
--
发表时间：
1985
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Caday,CG;Steiner,RF
通讯作者：
Steiner,RF
影响因子：
4.8
作者：
Cipolletta, E.;Monaco, S.;Illario, M.
通讯作者：
Illario, M.