Affinity labeling of the proteasome by a belactosin A derived inhibitor
Affinity labeling of the proteasome by a belactosin A derived inhibitor
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DOI：
10.1016/j.bmcl.2008.08.073
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发表时间：
2008-10-15
影响因子：
2.7
通讯作者：
Mizukami, Tamio
中科院分区：
文献类型：
--
作者：
Hasegawa, Makoto;Kinoshita, Kazuhiro;Mizukami, Tamio
Belactosin A是从链霉菌的代谢物中分离出来的一种有效的蛋白酶体抑制剂。在这里，我们证明了一种疏水的乳杆菌素a衍生物danyl - kf33955可以共价和特异性地亲和标记26S蛋白酶体的催化亚基，该蛋白酶体由20S蛋白质降解核心颗粒和19S调节颗粒组成。催化亚基的标记在体内完整的蛋白酶体中比在分离的20S核心颗粒中进行得更快。这些数据表明，19S调控颗粒可能有助于抑制剂进入20S核心颗粒。这种细胞渗透性化学探针是研究完整细胞中蛋白酶体抑制剂与蛋白酶体相互作用的极好工具。(C) 2008 Elsevier Ltd版权所有。
Belactosin A is a potent proteasome inhibitor isolated from Streptomyces metabolites. Here we show that a hydrophobic belactosin A derivative, dansyl-KF33955, can covalently, and specifically, affinity label the catalytic subunits of the 26S proteasome, which consists of the 20S protein degrading core particle and the 19S regulatory particles. The labeling of catalytic subunits proceeds faster in intact proteasomes in vivo than in isolated 20S core particles. These data suggest that the 19S regulatory particle may facilitate entry of the inhibitor into the 20S core particle. This cell-permeable chemical probe is an excellent tool with which to study the interactions of this proteasome inhibitor with proteasomes in intact cells. (C) 2008 Elsevier Ltd. All rights reserved.