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

ABSTRACT: 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.

SUBMITTER: Gundogdu M 

PROVIDER: S-EPMC5967971 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature