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

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...

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Autores principales: Gundogdu, Mehmet, Llabrés, Salomé, Gorelik, Andrii, Ferenbach, Andrew T., Zachariae, Ulrich, van Aalten, Daan M.F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2018
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5967971/
https://www.ncbi.nlm.nih.gov/pubmed/29606577
http://dx.doi.org/10.1016/j.chembiol.2018.03.004
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author Gundogdu, Mehmet
Llabrés, Salomé
Gorelik, Andrii
Ferenbach, Andrew T.
Zachariae, Ulrich
van Aalten, Daan M.F.
author_facet Gundogdu, Mehmet
Llabrés, Salomé
Gorelik, Andrii
Ferenbach, Andrew T.
Zachariae, Ulrich
van Aalten, Daan M.F.
author_sort Gundogdu, Mehmet
collection PubMed
description 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.
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spelling pubmed-59679712018-05-31 The O-GlcNAc Transferase Intellectual Disability Mutation L254F Distorts the TPR Helix Gundogdu, Mehmet Llabrés, Salomé Gorelik, Andrii Ferenbach, Andrew T. Zachariae, Ulrich van Aalten, Daan M.F. Cell Chem Biol Article 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. Cell Press 2018-05-17 /pmc/articles/PMC5967971/ /pubmed/29606577 http://dx.doi.org/10.1016/j.chembiol.2018.03.004 Text en © 2018 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gundogdu, Mehmet
Llabrés, Salomé
Gorelik, Andrii
Ferenbach, Andrew T.
Zachariae, Ulrich
van Aalten, Daan M.F.
The O-GlcNAc Transferase Intellectual Disability Mutation L254F Distorts the TPR Helix
title The O-GlcNAc Transferase Intellectual Disability Mutation L254F Distorts the TPR Helix
title_full The O-GlcNAc Transferase Intellectual Disability Mutation L254F Distorts the TPR Helix
title_fullStr The O-GlcNAc Transferase Intellectual Disability Mutation L254F Distorts the TPR Helix
title_full_unstemmed The O-GlcNAc Transferase Intellectual Disability Mutation L254F Distorts the TPR Helix
title_short The O-GlcNAc Transferase Intellectual Disability Mutation L254F Distorts the TPR Helix
title_sort o-glcnac transferase intellectual disability mutation l254f distorts the tpr helix
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5967971/
https://www.ncbi.nlm.nih.gov/pubmed/29606577
http://dx.doi.org/10.1016/j.chembiol.2018.03.004
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