O-GlcNAc transferase invokes nucleotide sugar pyrophosphate participation in catalysis

Marianne Schimpl, Xiaowei Zheng, Vladimir S. Borodkin, David E. Blair, Andrew T. Ferenbach, Alexander W. Schüttelkopf, Iva Navratilova, Tonia Aristotelous, Osama Albarbarawi, David A. Robinson, Daan M.F. van Aalten, Megan A. Macnaughtan

    Research output: Contribution to journalArticlepeer-review

    116 Citations (Scopus)


    Protein O-GlcNAcylation is an essential post-translational modification on hundreds of intracellular proteins in metazoa, catalyzed by O-linked ß-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 a-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.
    Original languageEnglish
    JournalNature Chemical Biology
    Early online date28 Oct 2012
    Publication statusPublished - 2012


    Dive into the research topics of 'O-GlcNAc transferase invokes nucleotide sugar pyrophosphate participation in catalysis'. Together they form a unique fingerprint.

    Cite this