The O-GlcNAc Transferase Intellectual Disability Mutation L254F Distorts the TPR Helix

Mehmet Gundogdu, Salome Llabres, Andrii Gorelik, Andrew Ferenbach, Ulrich Zachariae, Daan Van Aalten (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)
188 Downloads (Pure)


O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT) regulates protein O-GlcNAcylation, an essential post-translational modification that is abundant in the brain. Recently, OGT mutations have been associated with intellectual disability, although it is not understood how they affect OGT structure and function. Using a multi-disciplinary approach we show that the L254F OGT mutation leads to conformational changes of the tetratricopeptide repeats and reduced activity, revealing the molecular mechanisms contributing to pathogenesis.
Original languageEnglish
Pages (from-to)513-518.e4
Number of pages10
JournalCell Chemical Biology
Issue number5
Early online date29 Mar 2018
Publication statusPublished - 17 May 2018


  • O-GlcNAc transferase
  • intellectual disability
  • tandem repeat proteins
  • tetratricopeptide repeats
  • molecular dynamics simulations
  • crystallography

ASJC Scopus subject areas

  • Drug Discovery
  • Molecular Medicine
  • Molecular Biology
  • Biochemistry
  • Clinical Biochemistry
  • Pharmacology


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