Allosteric Targeting of the Fanconi Anemia Ubiquitin-Conjugating Enzyme Ube2T by Fragment Screening

[Image: see text] Ube2T is the E2 ubiquitin-conjugating enzyme of the Fanconi anemia DNA repair pathway and it is overexpressed in several cancers, representing an attractive target for the development of inhibitors. Despite the extensive efforts in targeting the ubiquitin system, very few E2 binder...

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Autores principales: Morreale, Francesca E., Bortoluzzi, Alessio, Chaugule, Viduth K., Arkinson, Connor, Walden, Helen, Ciulli, Alessio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2017
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5441753/
https://www.ncbi.nlm.nih.gov/pubmed/28437106
http://dx.doi.org/10.1021/acs.jmedchem.7b00147
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author Morreale, Francesca E.
Bortoluzzi, Alessio
Chaugule, Viduth K.
Arkinson, Connor
Walden, Helen
Ciulli, Alessio
author_facet Morreale, Francesca E.
Bortoluzzi, Alessio
Chaugule, Viduth K.
Arkinson, Connor
Walden, Helen
Ciulli, Alessio
author_sort Morreale, Francesca E.
collection PubMed
description [Image: see text] Ube2T is the E2 ubiquitin-conjugating enzyme of the Fanconi anemia DNA repair pathway and it is overexpressed in several cancers, representing an attractive target for the development of inhibitors. Despite the extensive efforts in targeting the ubiquitin system, very few E2 binders have currently been discovered. Herein we report the identification of a new allosteric pocket on Ube2T through a fragment screening using biophysical methods. Several fragments binding to this site inhibit ubiquitin conjugation in vitro.
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spelling pubmed-54417532017-05-24 Allosteric Targeting of the Fanconi Anemia Ubiquitin-Conjugating Enzyme Ube2T by Fragment Screening Morreale, Francesca E. Bortoluzzi, Alessio Chaugule, Viduth K. Arkinson, Connor Walden, Helen Ciulli, Alessio J Med Chem [Image: see text] Ube2T is the E2 ubiquitin-conjugating enzyme of the Fanconi anemia DNA repair pathway and it is overexpressed in several cancers, representing an attractive target for the development of inhibitors. Despite the extensive efforts in targeting the ubiquitin system, very few E2 binders have currently been discovered. Herein we report the identification of a new allosteric pocket on Ube2T through a fragment screening using biophysical methods. Several fragments binding to this site inhibit ubiquitin conjugation in vitro. American Chemical Society 2017-04-24 2017-05-11 /pmc/articles/PMC5441753/ /pubmed/28437106 http://dx.doi.org/10.1021/acs.jmedchem.7b00147 Text en Copyright © 2017 American Chemical Society This is an open access article published under a Creative Commons Attribution (CC-BY) License (http://pubs.acs.org/page/policy/authorchoice_ccby_termsofuse.html) , which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
spellingShingle Morreale, Francesca E.
Bortoluzzi, Alessio
Chaugule, Viduth K.
Arkinson, Connor
Walden, Helen
Ciulli, Alessio
Allosteric Targeting of the Fanconi Anemia Ubiquitin-Conjugating Enzyme Ube2T by Fragment Screening
title Allosteric Targeting of the Fanconi Anemia Ubiquitin-Conjugating Enzyme Ube2T by Fragment Screening
title_full Allosteric Targeting of the Fanconi Anemia Ubiquitin-Conjugating Enzyme Ube2T by Fragment Screening
title_fullStr Allosteric Targeting of the Fanconi Anemia Ubiquitin-Conjugating Enzyme Ube2T by Fragment Screening
title_full_unstemmed Allosteric Targeting of the Fanconi Anemia Ubiquitin-Conjugating Enzyme Ube2T by Fragment Screening
title_short Allosteric Targeting of the Fanconi Anemia Ubiquitin-Conjugating Enzyme Ube2T by Fragment Screening
title_sort allosteric targeting of the fanconi anemia ubiquitin-conjugating enzyme ube2t by fragment screening
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5441753/
https://www.ncbi.nlm.nih.gov/pubmed/28437106
http://dx.doi.org/10.1021/acs.jmedchem.7b00147
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