蛋白质精氨酸脱亚氨酶介导的蛋白质瓜氨酸化的化学生物学
Chemical biology of protein citrullination by the protein A arginine deiminases.
作者信息
Mondal Santanu, Thompson Paul R
机构信息
Department of Biochemistry and Molecular Pharmacology, UMass Medical School, 364 Plantation Street, Worcester, MA, 01605, USA; Program in Chemical Biology, UMass Medical School, 364 Plantation Street, Worcester, MA, 01605, USA.
Department of Biochemistry and Molecular Pharmacology, UMass Medical School, 364 Plantation Street, Worcester, MA, 01605, USA; Program in Chemical Biology, UMass Medical School, 364 Plantation Street, Worcester, MA, 01605, USA.
出版信息
Curr Opin Chem Biol. 2021 Aug;63:19-27. doi: 10.1016/j.cbpa.2021.01.010. Epub 2021 Mar 4.
Citrullination is a post-translational modification (PTM) that converts peptidyl-arginine into peptidyl-citrulline; citrullination is catalyzed by the protein arginine deiminases (PADs). This PTM is associated with several physiological processes, including the epigenetic regulation of gene expression, neutrophil extracellular trap formation, and DNA-damage induced apoptosis. Notably, aberrant protein citrullination is relevant to several autoimmune and neurodegenerative diseases and certain forms of cancer. As such, the PADs are promising therapeutic targets. In this review, we discuss recent advances in the development of PAD inhibitors and activity-based probes, the development and use of citrulline-specific probes in chemoproteomic applications, and methods to site-specifically incorporate citrulline into proteins.
瓜氨酸化是一种翻译后修饰（PTM），可将肽基精氨酸转化为肽基瓜氨酸；瓜氨酸化由蛋白质精氨酸脱亚氨酶（PADs）催化。这种PTM与多种生理过程相关，包括基因表达的表观遗传调控、中性粒细胞胞外陷阱形成以及DNA损伤诱导的细胞凋亡。值得注意的是，异常的蛋白质瓜氨酸化与多种自身免疫性疾病、神经退行性疾病以及某些形式的癌症有关。因此，PADs是很有前景的治疗靶点。在本综述中，我们讨论了PAD抑制剂和基于活性的探针开发的最新进展、瓜氨酸特异性探针在化学蛋白质组学应用中的开发和使用，以及将瓜氨酸位点特异性掺入蛋白质的方法。
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