Se-adenosyl-L-selenomethionine cofactor analogue as a reporter of protein methylation.
Se-adenosyl-L-selenomethionine cofactor analogue as a reporter of protein methylation.
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DOI:
10.1021/ja304782r
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发表时间:
2012-09-12
影响因子:
15
通讯作者:
Luo M
中科院分区:
文献类型:
--
作者:
Bothwell IR;Islam K;Chen Y;Zheng W;Blum G;Deng H;Luo M
Posttranslational methylation by S-adenosyl-L-methionine(SAM)-dependent methyltransferases plays essential roles in modulating protein function in both normal and disease states. As such, there is a growing need to develop chemical reporters to examine the physiological and pathological roles of protein methyltransferases. Several sterically bulky SAM analogues have previously been used to label substrates of specific protein methyltransferases. However, broad application of these compounds has been limited by their general incompatibility with native enzymes. Here we report a SAM surrogate, ProSeAM (propargylic Se-adenosyl-L-selenomethionine), as a reporter of methyltransferases. ProSeAM can be processed by multiple protein methyltransferases for substrate labeling. In contrast, sulfur-based propargylic SAM undergoes rapid decomposition at physiological pH, likely via an allene intermediate. In conjunction with fluorescent/affinity-based azide probes, copper-catalyzed azide-alkyne cycloaddition chemistry, in-gel fluorescence visualization and proteomic analysis, we further demonstrated ProSeAM’s utility to profile substrates of endogenous methyltransferases in diverse cellular contexts. These results thus feature ProSeAM as a convenient probe to study the activities of endogenous protein methyltransferases.
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影响因子:
16.6
作者:
Chang, Pamela V.;Chen, Xing;Smyrniotis, Chris;Xenakis, Alexander;Hu, Tianshun;Bertozzi, Carolyn R.;Wu, Peng
通讯作者:
Wu, Peng
影响因子:
18.3
作者:
Hang, Howard C.;Wilson, John P.;Charron, Guillaume
通讯作者:
Charron, Guillaume
影响因子:
64.8
作者:
通讯作者:
--
影响因子:
5.3
作者:
O'Carroll, D;Scherthan, H;Jenuwein, T
通讯作者:
Jenuwein, T
影响因子:
2.9
作者:
Iwig, DF;Booker, SJ
通讯作者:
Booker, SJ