Structural and Functional Basis of JAMM Deubiquitinating Enzymes in Disease.
Structural and Functional Basis of JAMM Deubiquitinating Enzymes in Disease.
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DOI：
10.3390/biom12070910
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发表时间：
2022-06-29
期刊：
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
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去泛素化酶（DUBs）是一类通过调节泛素化和去泛素化之间的平衡来维持细胞内稳态的重要蛋白酶。JAB 1/MPN/Mov 34金属酶（JAMM）是DUB中唯一已知的金属蛋白酶家族，与肿瘤发生、免疫和炎症性疾病在多个水平特异性相关。JAMM的数量少得多，催化机制独特，使其成为有吸引力的药物靶标。目前，已经成功开发了几种JAMM抑制剂，并显示出良好的治疗效果。为了更好地了解JAMM，本文重点介绍了该家族中的几个关键蛋白，包括AMSH、AMSH-LP、BRCC 36、Rpn 11和CSN 5，并着重讨论了它们的结构基础、不同功能、催化机制以及目前报道的针对JAMM的抑制剂。这些进展为利用JAMM作为治疗各种疾病的靶点奠定了基础。
Deubiquitinating enzymes (DUBs) are a group of proteases that are important for maintaining cell homeostasis by regulating the balance between ubiquitination and deubiquitination. As the only known metalloproteinase family of DUBs, JAB1/MPN/Mov34 metalloenzymes (JAMMs) are specifically associated with tumorigenesis and immunological and inflammatory diseases at multiple levels. The far smaller numbers and distinct catalytic mechanism of JAMMs render them attractive drug targets. Currently, several JAMM inhibitors have been successfully developed and have shown promising therapeutic efficacy. To gain greater insight into JAMMs, in this review, we focus on several key proteins in this family, including AMSH, AMSH-LP, BRCC36, Rpn11, and CSN5, and emphatically discuss their structural basis, diverse functions, catalytic mechanism, and current reported inhibitors targeting JAMMs. These advances set the stage for the exploitation of JAMMs as a target for the treatment of various diseases.
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