8‐Chloro‐dGTP, a hypochlorous acid‐modified nucleotide, is hydrolyzed by hMTH1, the human MutT homolog
Open Access
- 17 January 2002
- journal article
- Published by Wiley in FEBS Letters
- Vol. 512 (1-3) , 149-151
- https://doi.org/10.1016/s0014-5793(02)02240-8
Abstract
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.Keywords
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