Posttranslational modifications of proteins are often key to understanding their biological function, localization, and fate. In particular, the covalent attachment of ubiquitin, a small 76-amino acid polypeptide, to substrates has attracted recent attention and is being exploited to generate novel drugs capable of removing pathogenic targets in a selective fashion (proteolysis-targeting chimeras) (1). Conjugation of ubiquitin can be reversed by deubiquitinating enzymes (DUBs), reflecting additional regulation (2). Control for reversing protein ubiquitylation has been the subject of Satpal Virdee and coworkers (3), who have developed a DUB amino acid profiling assay that led to the discovery of a class of ubiquitin esterases, classically assigned as ubiquitin specific proteases. As reported in PNAS, the authors show, for a subset of DUBs from the Machado−Josephin Domain (MJD) family, previously with unknown function, their ability to cleave ubiquitin not only from lysine-based “classical” isopeptide bonds but also from ubiquitin moieties linked to serine and threonine side chains via ester linkages (3).

中文翻译：

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DUB酯酶活性进一步解码泛素的谜团[生物化学]

蛋白质的翻译后修饰通常是理解其生物学功能，定位和命运的关键。特别地，泛素（一种76个氨基酸的小多肽）与底物的共价连接引起了最近的关注，并被用于开发能够以选择性方式（靶向蛋白水解的嵌合体）去除病原体的新型药物（1）。泛素化酶（DUBs）可以逆转泛素的结合，这反映了额外的调节作用（2）。逆转蛋白质泛素化的控制已成为Satpal Virdee及其同事的课题（3），他们开发了DUB氨基酸谱分析方法，从而发现了一类泛素酯酶，通常被称为泛素特异性蛋白酶。正如PNAS报道的那样，作者显示，对于以前未知功能的Machado-Josephin域（MJD）系列DUB的子集，它们不仅能够从基于赖氨酸的“经典”异肽键上切割泛素，而且还可以从泛素上裂解泛素。通过酯键与丝氨酸和苏氨酸侧链相连的部分（3）。