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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3834327?pdf=render |
| _version_ | 1818838596525752320 |
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| author | Claire Amiable Sylvie Pochet André Padilla Gilles Labesse Pierre Alexandre Kaminski |
| author_facet | Claire Amiable Sylvie Pochet André Padilla Gilles Labesse Pierre Alexandre Kaminski |
| author_sort | Claire Amiable |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T03:40:55Z |
| format | Article |
| id | doaj.art-98ea3adf9c284834a2d3cdcf4cbed64b |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-19T03:40:55Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-98ea3adf9c284834a2d3cdcf4cbed64b2022-12-21T20:37:13ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01811e8075510.1371/journal.pone.0080755N (6)-substituted AMPs inhibit mammalian deoxynucleotide N-hydrolase DNPH1.Claire AmiableSylvie PochetAndré PadillaGilles LabessePierre Alexandre KaminskiThe 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.http://europepmc.org/articles/PMC3834327?pdf=render |
| spellingShingle | Claire Amiable Sylvie Pochet André Padilla Gilles Labesse Pierre Alexandre Kaminski N (6)-substituted AMPs inhibit mammalian deoxynucleotide N-hydrolase DNPH1. PLoS ONE |
| 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 |
| url | http://europepmc.org/articles/PMC3834327?pdf=render |
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