Structural highlights
Function
[DNPH1_RAT] Catalyzes the cleavage of the N-glycosidic bond of deoxyribonucleoside 5'-monophosphates to yield deoxyribose 5-phosphate and a purine or pyrimidine base. Deoxyribonucleoside 5'-monophosphates containing purine bases are preferred to those containing pyrimidine bases.[1]
Publication Abstract from PubMed
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.
N (6)-substituted AMPs inhibit mammalian deoxynucleotide N-hydrolase DNPH1.,Amiable C, Pochet S, Padilla A, Labesse G, Kaminski PA PLoS One. 2013 Nov 19;8(11):e80755. doi: 10.1371/journal.pone.0080755., eCollection 2013. PMID:24260472[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ghiorghi YK, Zeller KI, Dang CV, Kaminski PA. The c-Myc target gene Rcl (C6orf108) encodes a novel enzyme, deoxynucleoside 5'-monophosphate N-glycosidase. J Biol Chem. 2007 Mar 16;282(11):8150-6. Epub 2007 Jan 18. PMID:17234634 doi:http://dx.doi.org/10.1074/jbc.M610648200
- ↑ Amiable C, Pochet S, Padilla A, Labesse G, Kaminski PA. N (6)-substituted AMPs inhibit mammalian deoxynucleotide N-hydrolase DNPH1. PLoS One. 2013 Nov 19;8(11):e80755. doi: 10.1371/journal.pone.0080755., eCollection 2013. PMID:24260472 doi:http://dx.doi.org/10.1371/journal.pone.0080755
