Inhibitory study of protein arginine methyltransferase 1 using a fluorescent approach
Inhibitory study of protein arginine methyltransferase 1 using a fluorescent approach
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DOI：
10.1016/j.bbrc.2008.12.119
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发表时间：
2009-02-06
影响因子：
3.1
通讯作者：
Zheng, Yujun George
中科院分区：
文献类型：
--
作者：
Feng, You;Xie, Nan;Zheng, Yujun George
蛋白质精氨酸甲基转移酶(PRMTs)在正常生理和人类疾病中都发挥着重要作用。PRMT活性的放松与几种病理状态有关，如癌症(原发疾病)和心血管疾病。在此，我们报道了我们设计和使用新的荧光报告分子对PRMT1底物结合和甲基化进行单STP分析的工作。R4-FL和H4-FL的荧光(SIC)和各向异性都有效地促进了酶-SIC的相互作用，突出了它们在研究PRMT抑制剂方面的应用。特别是，利用荧光强度读数可以直接研究R4-FL的(SIC)甲基化过程。结合荧光检测和放射性分析，我们确定AML-1通过阻断多肽底物结合的机制抑制PRMT1的活性。(C)2008年爱思唯尔。版权所有。
Protein arginine methyltransferases (PRMTs) play important roles in both noraml physiology and human diseases. Deregulation of PRMT activity has been linked to several pathological states such as cancer (sic) cardiovascular disorders. Herein, we report our work of designing and using new fluorescent reporter to perform single-stp analysis of substrate binding and methylation by PRMT1. Both fluorescence (sic) and anisotropy of the two reporters, R4-FL and H4-FL, were shown to effectively maifest enzyme-(sic) strate interaction, highlighting their application in investigating PRMT inhibitors. In particular, (sic) methylation process of R4-FL can be directly studied using fluorescence intensity readout. By combining the fluorescent measurement with radioactive analysis, we determined that AMl-1 inhibits PRMT1 activity through the mechanism of blocking peptide substrate binding. (C) 2008 Elsevier Ince. All rights reserved.