分子检测破解 O-GlcNAc 案例
Molecular Interrogation to Crack the Case of O-GlcNAc.
机构信息
Pharmaceutical Sciences Division, University of Wisconsin-Madison, Madison, WI, 53705, USA.
出版信息
Chemistry. 2020 Sep 21;26(53):12086-12100. doi: 10.1002/chem.202000155. Epub 2020 Jul 20.
Abstract
The O-linked β-N-acetylglucosamine (O-GlcNAc) modification, termed O-GlcNAcylation, is an essential and dynamic post-translational modification in cells. O-GlcNAc transferase (OGT) installs this modification on serine and threonine residues, whereas O-GlcNAcase (OGA) hydrolyzes it. O-GlcNAc modifications are found on thousands of intracellular proteins involved in diverse biological processes. Dysregulation of O-GlcNAcylation and O-GlcNAc cycling enzymes has been detected in many diseases, including cancer, diabetes, cardiovascular and neurodegenerative diseases. Here, recent advances in the development of molecular tools to investigate OGT and OGA functions and substrate recognition are discussed. New chemical approaches to study O-GlcNAc dynamics and its potential roles in the immune system are also highlighted. It is hoped that this minireview will encourage more research in these areas to advance the understanding of O-GlcNAc in biology and diseases.
摘要
O-连接的β-N-乙酰氨基葡萄糖（O-GlcNAc）修饰，称为 O-GlcNAcylation，是细胞中一种必需且动态的翻译后修饰。O-连接的 N-乙酰氨基葡萄糖转移酶（OGT）将该修饰安装在丝氨酸和苏氨酸残基上，而 O-GlcNAcase（OGA）则将其水解。O-GlcNAc 修饰存在于数千种参与多种生物过程的细胞内蛋白上。在包括癌症、糖尿病、心血管疾病和神经退行性疾病在内的许多疾病中，都检测到了 O-GlcNAcylation 和 O-GlcNAc 循环酶的失调。本文讨论了用于研究 OGT 和 OGA 功能和底物识别的分子工具的最新进展。还强调了研究 O-GlcNAc 动态及其在免疫系统中潜在作用的新化学方法。希望这篇简评将鼓励更多的研究在这些领域开展，以推进对 O-GlcNAc 在生物学和疾病中的理解。
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