page_title: O-GlcNAc
section_title: Discovery
hierarchical_section_title: O-GlcNAc / Discovery
caption_attribution_description: English: GalT radiolabeling of cellular proteins with UDP-[3H]galactose followed by β-elimination yielded Galβ1-4GlcNAcitol, suggesting that the substrate for GalT was O-GlcNAc. Radiolabeled [3H]galactose shown in red.
context_page_description: O-GlcNAc is a reversible enzymatic post-translational modification that is found on serine and threonine residues of nucleocytoplasmic proteins. The modification is characterized by a β-glycosidic bond between the hydroxyl group of serine or threonine side chains and N-acetylglucosamine. O-GlcNAc differs from other forms of protein glycosylation: O-GlcNAc is not elongated or modified to form more complex glycan structures, O-GlcNAc is almost exclusively found on nuclear and cytoplasmic proteins rather than membrane proteins and secretory proteins, and O-GlcNAc is a highly dynamic modification that turns over more rapidly than the proteins which it modifies. O-GlcNAc is conserved across metazoans.
  Due to the dynamic nature of O-GlcNAc and its presence on serine and threonine residues, O-GlcNAcylation is similar to protein phosphorylation in some respects. While there are roughly 500 kinases and 150 phosphatases that regulate protein phosphorylation in humans, there are only 2 enzymes that regulate the cycling of O-GlcNAc: O-GlcNAc transferase and O-GlcNAcase catalyze the addition and removal of O-GlcNAc, respectively. OGT utilizes UDP-GlcNAc as the donor sugar for sugar transfer.
context_section_description: In 1984, the Hart lab was probing for terminal GlcNAc residues on the surfaces of thymocytes and lymphocytes. Bovine milk β-1,4-galactosyltransferase, which reacts with terminal GlcNAc residues, was used to perform radiolabeling with UDP-[³H]galactose. β-elimination of serine and threonine residues demonstrated that most of the [³H]galactose was attached to proteins O-glycosidically; chromatography revealed that the major β-elimination product was Galβ1-4GlcNAcitol. Insensitivity to peptide N-glycosidase treatment provided additional evidence for O-linked GlcNAc. Permeabilizing cells with detergent prior to radiolabeling greatly increased the amount of [³H]galactose incorporated into Galβ1-4GlcNAcitol, leading the authors to conclude that most of the O-linked GlcNAc monosaccharide residues were intracellular.
caption: GalT radiolabeling of cellular proteins with UDP-[3H]galactose followed by β-elimination yielded Galβ1-4GlcNAcitol, suggesting that the substrate for GalT was O-GlcNAc. Radiolabeled [3H]galactose shown in red.
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