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Overview of the Assays to Probe O-Linked β-N-Acetylglucosamine Transferase Binding and Activity

O-GlcNAcylation is a posttranslational modification that occurs at serine and threonine residues of protein substrates by the addition of O-linked β-d-N-acetylglucosamine (GlcNAc) moiety. Two enzymes are involved in this modification: O-GlcNac transferase (OGT), which attaches the GlcNAc residue to...

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Autores principales: Balsollier, Cyril, Pieters, Roland J., Anderluh, Marko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920051/
https://www.ncbi.nlm.nih.gov/pubmed/33669256
http://dx.doi.org/10.3390/molecules26041037
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author Balsollier, Cyril
Pieters, Roland J.
Anderluh, Marko
author_facet Balsollier, Cyril
Pieters, Roland J.
Anderluh, Marko
author_sort Balsollier, Cyril
collection PubMed
description O-GlcNAcylation is a posttranslational modification that occurs at serine and threonine residues of protein substrates by the addition of O-linked β-d-N-acetylglucosamine (GlcNAc) moiety. Two enzymes are involved in this modification: O-GlcNac transferase (OGT), which attaches the GlcNAc residue to the protein substrate, and O-GlcNAcase (OGA), which removes it. This biological balance is important for many biological processes, such as protein expression, cell apoptosis, and regulation of enzyme activity. The extent of this modification has sparked interest in the medical community to explore OGA and OGT as therapeutic targets, particularly in degenerative diseases. While some OGA inhibitors are already in phase 1 clinical trials for the treatment of Alzheimer’s disease, OGT inhibitors still have a long way to go. Due to complex expression and instability, the discovery of potent OGT inhibitors is challenging. Over the years, the field has grappled with this problem, and scientists have developed a number of techniques and assays. In this review, we aim to highlight assays and techniques for OGT inhibitor discovery, evaluate their strength for the field, and give us direction for future bioassay methods.
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spelling pubmed-79200512021-03-02 Overview of the Assays to Probe O-Linked β-N-Acetylglucosamine Transferase Binding and Activity Balsollier, Cyril Pieters, Roland J. Anderluh, Marko Molecules Review O-GlcNAcylation is a posttranslational modification that occurs at serine and threonine residues of protein substrates by the addition of O-linked β-d-N-acetylglucosamine (GlcNAc) moiety. Two enzymes are involved in this modification: O-GlcNac transferase (OGT), which attaches the GlcNAc residue to the protein substrate, and O-GlcNAcase (OGA), which removes it. This biological balance is important for many biological processes, such as protein expression, cell apoptosis, and regulation of enzyme activity. The extent of this modification has sparked interest in the medical community to explore OGA and OGT as therapeutic targets, particularly in degenerative diseases. While some OGA inhibitors are already in phase 1 clinical trials for the treatment of Alzheimer’s disease, OGT inhibitors still have a long way to go. Due to complex expression and instability, the discovery of potent OGT inhibitors is challenging. Over the years, the field has grappled with this problem, and scientists have developed a number of techniques and assays. In this review, we aim to highlight assays and techniques for OGT inhibitor discovery, evaluate their strength for the field, and give us direction for future bioassay methods. MDPI 2021-02-16 /pmc/articles/PMC7920051/ /pubmed/33669256 http://dx.doi.org/10.3390/molecules26041037 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Balsollier, Cyril
Pieters, Roland J.
Anderluh, Marko
Overview of the Assays to Probe O-Linked β-N-Acetylglucosamine Transferase Binding and Activity
title Overview of the Assays to Probe O-Linked β-N-Acetylglucosamine Transferase Binding and Activity
title_full Overview of the Assays to Probe O-Linked β-N-Acetylglucosamine Transferase Binding and Activity
title_fullStr Overview of the Assays to Probe O-Linked β-N-Acetylglucosamine Transferase Binding and Activity
title_full_unstemmed Overview of the Assays to Probe O-Linked β-N-Acetylglucosamine Transferase Binding and Activity
title_short Overview of the Assays to Probe O-Linked β-N-Acetylglucosamine Transferase Binding and Activity
title_sort overview of the assays to probe o-linked β-n-acetylglucosamine transferase binding and activity
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920051/
https://www.ncbi.nlm.nih.gov/pubmed/33669256
http://dx.doi.org/10.3390/molecules26041037
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