N (6)-Substituted AMPs Inhibit Mammalian Deoxynucleotide N-Hydrolase DNPH1

The gene dnph1 (or rcl) encodes a hydrolase that cleaves the 2’-deoxyribonucleoside 5’-monophosphate (dNMP) N-glycosidic bond to yield a free nucleobase and 2-deoxyribose 5-phosphate. Recently, the crystal structure of rat DNPH1, a potential target for anti-cancer therapies, suggested that various a...

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Autores principales: Amiable, Claire, Pochet, Sylvie, Padilla, André, Labesse, Gilles, Kaminski, Pierre Alexandre
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3834327/
https://www.ncbi.nlm.nih.gov/pubmed/24260472
http://dx.doi.org/10.1371/journal.pone.0080755
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author Amiable, Claire
Pochet, Sylvie
Padilla, André
Labesse, Gilles
Kaminski, Pierre Alexandre
author_facet Amiable, Claire
Pochet, Sylvie
Padilla, André
Labesse, Gilles
Kaminski, Pierre Alexandre
author_sort Amiable, Claire
collection PubMed
description The gene dnph1 (or rcl) encodes a hydrolase that cleaves the 2’-deoxyribonucleoside 5’-monophosphate (dNMP) N-glycosidic bond to yield a free nucleobase and 2-deoxyribose 5-phosphate. Recently, the crystal structure of rat DNPH1, a potential target for anti-cancer therapies, suggested that various analogs of AMP may inhibit this enzyme. From this result, we asked whether N (6)-substituted AMPs, and among them, cytotoxic cytokinin riboside 5’-monophosphates, may inhibit DNPH1. Here, we characterized the structural and thermodynamic aspects of the interactions of these various analogs with DNPH1. Our results indicate that DNPH1 is inhibited by cytotoxic cytokinins at concentrations that inhibit cell growth.
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spelling pubmed-38343272013-11-20 N (6)-Substituted AMPs Inhibit Mammalian Deoxynucleotide N-Hydrolase DNPH1 Amiable, Claire Pochet, Sylvie Padilla, André Labesse, Gilles Kaminski, Pierre Alexandre PLoS One Research Article The gene dnph1 (or rcl) encodes a hydrolase that cleaves the 2’-deoxyribonucleoside 5’-monophosphate (dNMP) N-glycosidic bond to yield a free nucleobase and 2-deoxyribose 5-phosphate. Recently, the crystal structure of rat DNPH1, a potential target for anti-cancer therapies, suggested that various analogs of AMP may inhibit this enzyme. From this result, we asked whether N (6)-substituted AMPs, and among them, cytotoxic cytokinin riboside 5’-monophosphates, may inhibit DNPH1. Here, we characterized the structural and thermodynamic aspects of the interactions of these various analogs with DNPH1. Our results indicate that DNPH1 is inhibited by cytotoxic cytokinins at concentrations that inhibit cell growth. Public Library of Science 2013-11-19 /pmc/articles/PMC3834327/ /pubmed/24260472 http://dx.doi.org/10.1371/journal.pone.0080755 Text en © 2013 Amiable et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Amiable, Claire
Pochet, Sylvie
Padilla, André
Labesse, Gilles
Kaminski, Pierre Alexandre
N (6)-Substituted AMPs Inhibit Mammalian Deoxynucleotide N-Hydrolase DNPH1
title N (6)-Substituted AMPs Inhibit Mammalian Deoxynucleotide N-Hydrolase DNPH1
title_full N (6)-Substituted AMPs Inhibit Mammalian Deoxynucleotide N-Hydrolase DNPH1
title_fullStr N (6)-Substituted AMPs Inhibit Mammalian Deoxynucleotide N-Hydrolase DNPH1
title_full_unstemmed N (6)-Substituted AMPs Inhibit Mammalian Deoxynucleotide N-Hydrolase DNPH1
title_short N (6)-Substituted AMPs Inhibit Mammalian Deoxynucleotide N-Hydrolase DNPH1
title_sort n (6)-substituted amps inhibit mammalian deoxynucleotide n-hydrolase dnph1
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3834327/
https://www.ncbi.nlm.nih.gov/pubmed/24260472
http://dx.doi.org/10.1371/journal.pone.0080755
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