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Updated: May 17, 2026

Spectrophotometric Methods for the Study of Eukaryotic Glycogen Metabolism
Published on: August 19, 2021
O-GlcNAc transferase invokes nucleotide sugar pyrophosphate participation in catalysis
Marianne Schimpl1, Xiaowei Zheng, Vladimir S Borodkin
1College of Life Sciences, University of Dundee, Dundee, UK.
Abstract:
Protein O-GlcNAcylation is an essential post-translational modification on hundreds of intracellular proteins in metazoa, catalyzed by O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) using unknown mechanisms of transfer and substrate recognition. Through crystallographic snapshots and mechanism-inspired chemical probes, we define how human OGT recognizes the sugar donor and acceptor peptide and uses a new catalytic mechanism of glycosyl transfer, involving the sugar donor α-phosphate as the catalytic base as well as an essential lysine. This mechanism seems to be a unique evolutionary solution to the spatial constraints imposed by a bulky protein acceptor substrate and explains the unexpected specificity of a recently reported metabolic OGT inhibitor.
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