Pranlukast, a novel binding ligand of human Raf1 kinase inhibitory protein
Pranlukast, a novel binding ligand of human Raf1 kinase inhibitory protein
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Pranlukast，一种新型人 Raf1 激酶抑制蛋白结合配体
DOI：
10.1007/s10529-016-2117-0
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发表时间：
2016-08-01
影响因子：
2.7
通讯作者：
Guo, Chenyun
中科院分区：
文献类型：
--
作者：
Sun, Tao;Wu, Zhihua;Guo, Chenyun
目的研究普仑司特与hRKIP的结合及其在Raf 1/MEK/ERK信号通路中的调节作用。hRKIP保守的配体结合口袋上的残基（Y81、S109和Y181）在结合普仑司特中起关键作用，并且它们的突变使结合亲和力降低超过85%。25 μ M的普仑司特可使ERK磷酸化水平上调约17%，普仑司特可作为治疗hRKIP相关疾病的潜在药物前体。
To study the binding of pranlukast to hRKIP and its regulatory role in the Raf1/MEK/ERK signal pathway.NMR and fluorescence experiments demonstrated hRKIP could bind pranlukast with a binding constant of 1016 mM(-1). Residues (Y81, S109 and Y181) on the conserved ligand-binding pocket of hRKIP played a crucial role in binding pranlukast, and their mutations reduced the binding affinity more than 85 %. Furthermore, 25 mu M pranlukast could up-regulate the ERK phosphorylation by about 17 %.Pranlukast may be used as a potential drug precursor for treating hRKIP involved diseases.