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Analytical and Biochemical Perspectives of Protein O-GlcNAcylation
Chemical Reviews ( IF 51.4 ) Pub Date : 2021-01-08 , DOI: 10.1021/acs.chemrev.0c00884
Junfeng Ma 1 , Ci Wu 1 , Gerald W Hart 2
Affiliation  

Protein O-linked β-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation) is a unique monosaccharide modification discovered in the early 1980s. With the technological advances in the past several decades, great progress has been made to reveal the biochemistry of O-GlcNAcylation, the substrates of O-GlcNAcylation, and the functional importance of protein O-GlcNAcylation. As a nutrient sensor, protein O-GlcNAcylation plays important roles in almost all biochemical processes examined. Although the functional importance of O-GlcNAcylation of proteins has been extensively reviewed previously, the chemical and biochemical aspects have not been fully addressed. In this review, by critically evaluating key publications in the past 35 years, we aim to provide a comprehensive understanding of this important post-translational modification (PTM) from analytical and biochemical perspectives. Specifically, we will cover (1) multiple analytical advances in the characterization of O-GlcNAc cycling components (i.e., the substrate donor UDP-GlcNAc, the two key enzymes O-GlcNAc transferase and O-GlcNAcase, and O-GlcNAc substrate proteins), (2) the biochemical characterization of the enzymes with a variety of chemical tools, and (3) exploration of O-GlcNAc cycling and its modulating chemicals as potential biomarkers and therapeutic drugs for diseases. Last but not least, we will discuss the challenges and possible solutions for basic and translational research of protein O-GlcNAcylation in the future.

中文翻译:

蛋白质 O-GlcNAcylation 的分析和生化观点

蛋白O-连接的β- N-乙酰氨基葡萄糖 (O-GlcNAc) 修饰 (O-GlcNAcylation) 是 80 年代早期发现的一种独特的单糖修饰。随着过去几十年的技术进步,在揭示 O-GlcNAcylation 的生物化学、O-GlcNAcylation 的底物和蛋白质 O-GlcNAcylation 的功能重要性方面取得了很大进展。作为营养传感器,蛋白质 O-GlcNAcylation 在几乎所有检查的生化过程中都起着重要作用。尽管蛋白质的 O-GlcNAcylation 的功能重要性之前已被广泛审查,但化学和生化方面尚未得到充分解决。在这篇评论中,通过批判性地评估过去 35 年的主要出版物,我们旨在从分析和生化的角度全面了解这一重要的翻译后修饰 (PTM)。具体来说,我们将介绍 (1) O-GlcNAc 循环成分(即底物供体 UDP-GlcNAc、两种关键酶 O-GlcNAc 转移酶和 O-GlcNAcase 以及 O-GlcNAc 底物蛋白)表征方面的多项分析进展, (2) 使用各种化学工具对酶进行生化表征,以及 (3) 探索 O-GlcNAc 循环及其调节化学物质作为潜在的生物标志物和疾病治疗药物。最后但同样重要的是,我们将讨论未来蛋白质 O-GlcNAcylation 基础和转化研究的挑战和可能的解决方案。我们将介绍 (1) O-GlcNAc 循环成分(即底物供体 UDP-GlcNAc、两种关键酶 O-GlcNAc 转移酶和 O-GlcNAcase 以及 O-GlcNAc 底物蛋白)表征方面的多项分析进展,( 2) 使用各种化学工具对酶进行生化表征,以及 (3) 探索 O-GlcNAc 循环及其调节化学物质作为潜在的生物标志物和疾病治疗药物。最后但同样重要的是,我们将讨论未来蛋白质 O-GlcNAcylation 基础和转化研究的挑战和可能的解决方案。我们将介绍 (1) O-GlcNAc 循环成分(即底物供体 UDP-GlcNAc、两种关键酶 O-GlcNAc 转移酶和 O-GlcNAcase 以及 O-GlcNAc 底物蛋白)表征方面的多项分析进展,( 2) 使用各种化学工具对酶进行生化表征,以及 (3) 探索 O-GlcNAc 循环及其调节化学物质作为潜在的生物标志物和疾病治疗药物。最后但同样重要的是,我们将讨论未来蛋白质 O-GlcNAcylation 基础和转化研究的挑战和可能的解决方案。(3) O-GlcNAc 循环及其调节化学物质作为潜在生物标志物和疾病治疗药物的探索。最后但同样重要的是,我们将讨论未来蛋白质 O-GlcNAcylation 基础和转化研究的挑战和可能的解决方案。(3) O-GlcNAc 循环及其调节化学物质作为潜在生物标志物和疾病治疗药物的探索。最后但同样重要的是,我们将讨论未来蛋白质 O-GlcNAcylation 基础和转化研究的挑战和可能的解决方案。
更新日期:2021-02-10
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