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© Institut Pasteur
Cristaux de cellulase, enzyme purifiée de Clostridium thermocellum permettant la digestion de la cellulose. Image colorisée.
Publication : PloS one

N (6)-substituted AMPs inhibit mammalian deoxynucleotide N-hydrolase DNPH1

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in PloS one - 19 Nov 2013

Amiable C, Pochet S, Padilla A, Labesse G, Kaminski PA

Link to Pubmed [PMID] – 24260472

PLoS ONE 2013;8(11):e80755

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.

http://www.ncbi.nlm.nih.gov/pubmed/24260472