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

N (6)-substituted AMPs inhibit mammalian deoxynucleotide N-hydrolase DNPH1.
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DOI:
10.1371/journal.pone.0080755
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Kaminski PA
Kaminski PA
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Amiable C;Pochet S;Padilla A;Labesse G;Kaminski PA

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基因dnph 1(或rcl)编码一种水解酶,可切割2 '-脱氧核苷5'-单磷酸(dNMP)N-糖苷键,产生游离核碱基和2-脱氧核糖5-磷酸。最近,大鼠DNPH 1(抗癌治疗的潜在靶点)的晶体结构表明,AMP的各种类似物可以抑制这种酶。从这个结果,我们问是否N6-取代的AMP,其中,细胞分裂素核苷5 '-单磷酸,可以抑制DNPH 1。在这里,我们的特点是这些不同的类似物与DNPH 1的相互作用的结构和热力学方面。我们的研究结果表明,DNPH 1抑制细胞分裂素的浓度,抑制细胞生长。
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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