Abstract
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.