Bisubstrate UDP-peptide conjugates as human O-GlcNAc transferase inhibitors

Vladimir S Borodkin, Marianne Schimpl, Mehmet Gundogdu, Karim Rafie, Helge C Dorfmueller, David A. Robinson, Daan M F van Aalten (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    37 Citations (Scopus)

    Abstract

    Inhibitors of OGT (O-GlcNAc transferase) are valuable tools to study the cell biology of protein O-GlcNAcylation. We report OGT bisubstrate-linked inhibitors (goblins) in which the acceptor serine in the peptide VTPVSTA is covalently linked to UDP, eliminating the GlcNAc pyranoside ring. Goblin1 co-crystallizes with OGT, revealing an ordered C3 linker and retained substrate-binding modes, and binds the enzyme with micromolar affinity, inhibiting glycosyltransfer on to protein and peptide substrates.
    Original languageEnglish
    Pages (from-to)497-502
    Number of pages6
    JournalBiochemical Journal
    Volume457
    Issue number3
    DOIs
    Publication statusPublished - 1 Feb 2014

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