Mechanisms, biology and inhibitors of deubiquitinating enzymes
Mechanisms, biology and inhibitors of deubiquitinating enzymes
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DOI：
10.1038/nchembio.2007.43
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发表时间：
2007-11-01
影响因子：
14.8
通讯作者：
Ploegh, Hidde L.
中科院分区：
文献类型：
--
作者：
Love, Kerry Routenberg;Catic, Andre;Ploegh, Hidde L.
泛素(Ub)和类泛素(Ubl)修饰物在蛋白质中起着调节功能的作用，是蛋白质降解、表观遗传修饰和细胞内定位的关键步骤。脱泛素酶和Ubl特异性蛋白水解酶负责去除Ub和Ubls，对泛素-蛋白酶体系统起到额外的控制作用。它们的保守性以及在真核生物、原核生物和病毒中的广泛存在表明，这些酶构成了一类重要的酶。在这里，我们讨论化学工具，包括基于活性的探针和自杀抑制剂，如何使(I)脱泛素化酶的发现，(Ii)它们的功能图谱，结晶学特征和机制分类，以及(Iii)用于治疗目的的分子的发展。
The addition of ubiquitin (Ub) and ubiquitin-like (Ubl) modifiers to proteins serves to modulate function and is a key step in protein degradation, epigenetic modification and intracellular localization. Deubiquitinating enzymes and Ubl-specific proteases, the proteins responsible for the removal of Ub and Ubls, act as an additional level of control over the ubiquitin-proteasome system. Their conservation and widespread occurrence in eukaryotes, prokaryotes and viruses shows that these proteases constitute an essential class of enzymes. Here, we discuss how chemical tools, including activity-based probes and suicide inhibitors, have enabled (i) discovery of deubiquitinating enzymes, (ii) their functional profiling, crystallographic characterization and mechanistic classification and (iii) development of molecules for therapeutic purposes.