title: Human MTH1 protein hydrolyzes the oxidized ribonucleotide, 2-hydroxy-ATP.
abstract: 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.
authors.affiliation: Department of Environmental Oncology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Fujikawa
authors.forename: H
authors.initials: H
authors.lastname: Kamiya
authors.forename: H
authors.initials: H
authors.lastname: Yakushiji
authors.forename: Y
authors.initials: Y
authors.lastname: Nakabeppu
authors.forename: H
authors.initials: H
authors.lastname: Kasai
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000378:metabolism*; D016587:Antimutagenic Agents / Q000378:metabolism*; D045643:DNA Repair Enzymes; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D010084:Oxidation-Reduction; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D017382:Reactive Oxygen Species; D012265:Ribonucleotides / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: C095141:2-hydroxydeoxyadenosine triphosphate; D016587:Antimutagenic Agents; D017382:Reactive Oxygen Species; D012265:Ribonucleotides; D000255:Adenosine Triphosphate; D010744:Phosphoric Monoester Hydrolases; C078207:8-oxodGTPase; D045643:DNA Repair Enzymes