Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison, 777 Highland Avenue, Madison, WI, 53705, USA.
Department of Chemistry, University of Wisconsin-Madison, 101 University Avenue, Madison, WI, 53706, USA.
Chembiochem. 2019 Feb 1;20(3):312-318. doi: 10.1002/cbic.201800481. Epub 2018 Nov 12.
The O-linked N-acetylglucosamine (O-GlcNAc) modification is an essential component in cell regulation. A single pair of human enzymes conducts this modification dynamically on a broad variety of proteins: O-GlcNAc transferase (OGT) adds the GlcNAc residue and O-GlcNAcase (OGA) hydrolyzes it. This modification is dysregulated in many diseases, but its exact effect on particular substrates remains unclear. In addition, no apparent sequence motif has been found in the modified proteins, and the factors controlling the substrate specificity of OGT and OGA are largely unknown. In this minireview, we will discuss recent developments in chemical and biochemical methods toward addressing the challenge of OGT and OGA substrate recognition. We hope that the new concepts and knowledge from these studies will promote research in this area to advance understanding of O-GlcNAc regulation in health and disease.
O-连接的 N-乙酰葡萄糖胺（O-GlcNAc）修饰是细胞调节的重要组成部分。一对人类酶能够在广泛的蛋白质上动态地进行这种修饰：O-连接的 N-乙酰葡萄糖胺转移酶（OGT）添加 GlcNAc 残基，而 O-连接的 N-乙酰葡萄糖胺水解酶（OGA）则将其水解。这种修饰在许多疾病中失调，但它对特定底物的确切影响仍不清楚。此外，在修饰的蛋白质中没有发现明显的序列模体，并且控制 OGT 和 OGA 底物特异性的因素在很大程度上尚不清楚。在这篇综述中，我们将讨论化学和生化方法的最新进展，以应对 OGT 和 OGA 底物识别的挑战。我们希望这些研究中的新概念和知识将促进该领域的研究，以加深对健康和疾病中 O-GlcNAc 调节的理解。
