8‐Chloro‐dGTP, a hypochlorous acid‐modified nucleotide, is hydrolyzed by hMTH1, the human MutT homolog

FEBS Letters

Yakushiji, Hiroyuki¹  Fujikawa, Katsuyoshi³  Masuda, Mitsuharu²  Ohshima, Hiroshi²  Kasai, Hiroshi³  Nakabeppu, Yusaku¹  Suzuki, Toshinori² 

[1] Department of Biochemistry, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan;International Agency for Research on Cancer, Unit of Endogenous Cancer Risk Factors, 150 Cours Albert-Thomas, 69372 Lyon Cedex 08, France;Department of Environmental Oncology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan

关键词: 8-Chloro-dGTP;    8-Hydroxy-dGTP;    hMTH1;    mutT;    Nucleotide sanitization enzyme;   

DOI  :  10.1016/S0014-5793(02)02240-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 μM 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.

【 授权许可】

Unknown