TY - JOUR
T1 - 8-Chloro-dGTP, a hypochlorous acid-modified nucleotide, is hydrolyzed by hMTH1, the human MutT homolog
AU - Fujikawa, Katsuyoshi
AU - Yakushiji, Hiroyuki
AU - Nakabeppu, Yusaku
AU - Suzuki, Toshinori
AU - Masuda, Mitsuharu
AU - Ohshima, Hiroshi
AU - Kasai, Hiroshi
N1 - Funding Information:
This work was supported in part by Grants-in Aid for Scientific Research on Priority Areas from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, and by a Grant-in-Aid for JSPS Fellows from the Japan Society for the Promotion of Science.
PY - 2002/2/13
Y1 - 2002/2/13
N2 - 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.
AB - 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.
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U2 - 10.1016/S0014-5793(02)02240-8
DO - 10.1016/S0014-5793(02)02240-8
M3 - Article
C2 - 11852070
AN - SCOPUS:0037070211
SN - 0014-5793
VL - 512
SP - 149
EP - 151
JO - FEBS Letters
JF - FEBS Letters
IS - 1-3
ER -