PLK1
Polo样激酶
激酶
底物特异性
基质(水族馆)
生物
生物化学
细胞生物学
计算生物学
化学
酶
细胞周期
基因
生态学
作者
Eric F. Johnson,Kent D. Stewart,Keith W. Woods,Vincent L. Giranda,Yan Luo
出处
期刊:Biochemistry
[American Chemical Society]
日期:2007-07-27
卷期号:46 (33): 9551-9563
被引量:101
摘要
PLK1 (polo-like kinase 1) is a key mitotic kinase and a therapeutic target in the treatment of proliferative diseases. Here we investigate the relative substrate specificity and pharmacological relatedness of PLK1, -2, -3, and -4 that together comprise a conserved family of Ser/Thr kinases (PLK family). We report consensus substrate sequences for PLK2, -3, and -4 and an expanded consensus sequence for PLK1, which we use to design an optimal peptide substrate, PLKtide. We report inhibitory activity for the entire PLK family across a diverse set of small-molecule ATP-competitive inhibitors including several clinical compounds. With respect to both substrate and ATP-site specificity, highest similarity is observed between PLK2 and PLK3, PLK1 is next most similar, and PLK4 is least similar. Further, we have identified and report time-dependent inhibition by two potent and selective PLK inhibitors.
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