Human MTH1 protein hydrolyzes the oxidized ribonucleotide, 2-hydroxy-ATP
Human MTH1 protein hydrolyzes the oxidized ribonucleotide, 2-hydroxy-ATP
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DOI：
10.1093/nar/29.2.449
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发表时间：
2001-01-15
影响因子：
14.9
通讯作者：
Kasai, H
中科院分区：
文献类型：
--
作者：
Fujikawa, K;Kamiya, H;Kasai, H
除8-羟基-dGTP外，人核苷酸池消毒酶MTH 1还水解2-羟基-dATP和8-羟基-dATP。我们在这里报告说，人类MTH 1是高度特异性的α-羟基-ATP，在同源的核糖核苷三磷酸。用高效液相色谱法测定了MTH 1对8-hydroxy-GTP、2-hydroxy-ATP和8-hydroxy-ATP的焦磷酸酶活性，动力学参数表明MTH 1对8-hydroxy-ATP的催化效率为2-hydroxy-ATP> 2-hydroxy-ATP > 8-hydroxy-GTP > 8-hydroxy-dATP >> dGTP > 8-hydroxy-GTP > 8-hydroxy-ATP。在已知底物中，MTH 1对β-羟基-ATP的亲和力最高，ATP参与能量代谢和信号转导，是RNA合成的前体。我们认为MTH 1的2-羟基-ATP水解活性可能阻止这些ATP相关途径的氧化ATP的扰动。
The human nucleotide pool sanitization enzyme, MTH1, hydrolyzes 2-hydroxy-dATP and 8-hydroxy-dATP in addition to 8-hydroxy-dGTP. We report here that human MTH1 is highly specific for a-hydroxy-ATP, among the cognate ribonucleoside triphosphates. The pyrophosphatase activities for 8-hydroxy-GTP, 2-hydroxy-ATP and 8-hydroxy-ATP were measured by high-performance liquid chromatography, The kinetic parameters thus obtained indicate that the catalytic efficiencies of MTH1 are in the order of 2-hydroxy-dATP > 2-hydroxy-ATP > 8-hydroxy-GTP > 8-hydroxy-dATP >> dGTP > 8-hydroxy-GTP > 8-hydroxy-ATP. Notably, MTH1 had the highest affinity for P-hydroxy-ATP among the known substrates, ATP is involved in energy metabolism and signal transduction, and is a precursor in RNA synthesis. We suggest that the 2-hydroxy-ATP hydrolyzing activity of MTH1 might prevent the perturbation of these ATP-related pathways by the oxidized ATP.