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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-7920051 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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