8-chloro-dGTP, a hypochlorous acid-modified nucleotide, is hydrolyzed by hMTH1, the human MutT homolog
8-chloro-dGTP, a hypochlorous acid-modified nucleotide, is hydrolyzed by hMTH1, the human MutT homolog
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DOI：
10.1016/s0014-5793(02)02240-8
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发表时间：
2002-02-13
期刊：
影响因子：
3.5
通讯作者：
Kasai, H
中科院分区：
文献类型：
--
作者：
Fujikawa, K;Yakushiji, H;Kasai, H
人类mutT同系物hMTH 1通过降解内源性诱变剂8-羟基-dGTP抑制自发突变。我们先前报道了hMTH 1的广泛底物特异性，除了8-羟基-dGTP外，它还降解氧化损伤的嘌呤核苷酸、2-羟基-dATP、8-羟基-dATP、2-羟基-ATP和8-羟基-GTP。在本文中，我们描述了8-氯-dGTP的hMTH 1活性，它可以在发炎组织中形成的dGTP与次氯酸，髓过氧化物酶的产品从激活的人中性粒细胞的反应。将hMTH 1蛋白与1-20 μ M的8-氯-dGTP和8-羟基-dGTP混合，并通过阴离子交换HPLC定量反应产物以测量焦磷酸酶反应速率。动力学参数表明，8-氯-dGTP被hMTH 1降解的50%的效率相比，8-羟基-dGTP。该结果表明，8-氯-dGTP是hMTH 1的内在底物。(C)2002年由Elsevier Science B. V.代表欧洲生物化学学会联合会出版。
The human mutT homolog, hMTH1, suppresses spontaneous mutations by degrading the endogeneous mutagen, 8-hydroxy-dGTP. We previously reported the broad substrate specificity of hMTH1, which also degrades the oxidatively damaged purine nucleotides, 2-hydroxy-dATP, 8-hydroxy-dATP, 2-hydroxy-ATP, and 8-hydroxy-GTP, in addition to 8-hydroxy-dGTP. In this paper, we describe the hMTH1 activity for 8-chloro-dGTP, which could be formed in inflamed tissue by the reaction of dGTP with hypochlorous acid, a product of myeloperoxidase from activated human neutrophils. The hMTH1 protein was mixed with 1-20 muM of 8-chloro-dGTP and 8-hydroxy-dGTP, and the reaction products were quantified by anion-exchange HPLC to measure the pyrophosphatase reaction rate. The kinetic parameters revealed that 8-chloro-dGTP was degraded by hMTH1 with 50% efficiency as compared with that of 8-hydroxy-dGTP. This result suggests that 8-chloro-dGTP is an intrinsic substrate for hMTH1. (C) 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.