人类MTH1蛋白可水解氧化型核糖核苷酸2-羟基-ATP。
Human MTH1 protein hydrolyzes the oxidized ribonucleotide, 2-hydroxy-ATP.
作者信息
Fujikawa K, Kamiya H, Yakushiji H, Nakabeppu Y, Kasai H
机构信息
Department of Environmental Oncology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan.
出版信息
Nucleic Acids Res. 2001 Jan 15;29(2):449-54. doi: 10.1093/nar/29.2.449.
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 2-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-dGTP > 8-hydroxy-dATP >> dGTP > 8-hydroxy-GTP > 8-hydroxy-ATP. Notably, MTH1 had the highest affinity for 2-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.
人类核苷酸池净化酶MTH1除了能水解8-羟基-dGTP外，还能水解2-羟基-dATP和8-羟基-dATP。我们在此报告，在同源核糖核苷三磷酸中，人类MTH1对2-羟基-ATP具有高度特异性。通过高效液相色谱法测定了8-羟基-GTP、2-羟基-ATP和8-羟基-ATP的焦磷酸酶活性。由此获得的动力学参数表明，MTH1的催化效率顺序为2-羟基-dATP > 2-羟基-ATP > 8-羟基-dGTP > 8-羟基-dATP >> dGTP > 8-羟基-GTP > 8-羟基-ATP。值得注意的是，在已知底物中，MTH1对2-羟基-ATP的亲和力最高。ATP参与能量代谢和信号转导，并且是RNA合成的前体。我们认为，MTH1的2-羟基-ATP水解活性可能会防止氧化型ATP对这些与ATP相关的途径造成干扰。
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