O-linked β-N-acetyl--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.
O-linked β-N-acetyl--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.
