title: NUDT5 hydrolyzes oxidized deoxyribonucleoside diphosphates with broad substrate specificity.
abstract: The human NUDT5 protein catalyzes the hydrolysis of 8-hydroxy-dGDP. To examine its substrate specificity, four oxidized deoxyribonucleotides (2-hydroxy-dADP, 8-hydroxy-dADP, 5-formyl-dUDP, and 5-hydroxy-dCDP) were incubated with the NUDT5 protein. Interestingly, all of the nucleotides, except for 5-hydroxy-dCDP, were hydrolyzed with various efficiencies. The kinetic parameters indicated that 8-hydroxy-dADP was hydrolyzed as efficiently as 8-hydroxy-dGDP. The hydrolyzing activities for their triphosphate counterparts were quite weak. These results suggest that the NUDT5 protein eliminates various oxidized deoxyribonucleoside diphosphates from the nucleotide pool and prevents their toxic effects.
authors.affiliation: Hokkaido University, Sapporo, Japan. hirokam@pharm.hokudai.ac.jp
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kamiya
authors.forename: Mika
authors.initials: M
authors.lastname: Hori
authors.forename: Takao
authors.initials: T
authors.lastname: Arimori
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Sekiguchi
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Yamagata
authors.forename: Hideyoshi
authors.initials: H
authors.lastname: Harashima
mesh_terms: D003853:Deoxyribonucleosides / Q000737:chemistry / Q000378:metabolism*; D011756:Diphosphates / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D010084:Oxidation-Reduction; D011755:Pyrophosphatases / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D003853:Deoxyribonucleosides; D011756:Diphosphates; C403715:NUDT5 protein, human; D011755:Pyrophosphatases