Nucleic Acids Research, 2001, Vol. 29, No. 2 449-454
© 2001 Oxford University Press
Human MTH1 protein hydrolyzes the oxidized ribonucleotide, 2-hydroxy-ATP
Department of Environmental Oncology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan, 1Department of Biochemistry, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan and 2CREST, Japan Science and Technology, Japan
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.
* To whom correspondence should be addressed. Tel: +81 93 691 7468; Fax: +81 93 601 2199; Email: h-kasai{at}med.uoeh-u.ac.jp Present address: Hiroyuki Kamiya, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060–0812, Japan
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  K. Yoshimura, T. Ogawa, Y. Ueda, and S. Shigeoka AtNUDX1, an 8-Oxo-7,8-Dihydro-2'-Deoxyguanosine 5'-Triphosphate Pyrophosphohydrolase, is Responsible for Eliminating Oxidized Nucleotides in Arabidopsis Plant Cell Physiol., October 1, 2007; 48(10): 1438 - 1449. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Kamiya, C. Cadena-Amaro, L. Dugue, H. Yakushiji, N. Minakawa, A. Matsuda, S. Pochet, Y. Nakabeppu, and H. Harashima Recognition of Nucleotide Analogs Containing the 7,8-Dihydro-8-oxo Structure by the Human MTH1 Protein J. Biochem., December 1, 2006; 140(6): 843 - 849. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Ushijima, Y. Tominaga, T. Miura, D. Tsuchimoto, K. Sakumi, and Y. Nakabeppu A functional analysis of the DNA glycosylase activity of mouse MUTYH protein excising 2-hydroxyadenine opposite guanine in DNA Nucleic Acids Res., January 28, 2005; 33(2): 672 - 682. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Nunoshiba, R. Ishida, M. Sasaki, S. Iwai, Y. Nakabeppu, and K. Yamamoto A novel Nudix hydrolase for oxidized purine nucleoside triphosphates encoded by ORFYLR151c (PCD1 gene) in Saccharomyces cerevisiae Nucleic Acids Res., October 8, 2004; 32(18): 5339 - 5348. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Mishima, Y. Sakai, N. Itoh, H. Kamiya, M. Furuichi, M. Takahashi, Y. Yamagata, S. Iwai, Y. Nakabeppu, and M. Shirakawa Structure of Human MTH1, a Nudix Family Hydrolase That Selectively Degrades Oxidized Purine Nucleoside Triphosphates J. Biol. Chem., August 6, 2004; 279(32): 33806 - 33815. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Yoshimura, K. Sakumi, M. Ohno, Y. Sakai, M. Furuichi, S. Iwai, and Y. Nakabeppu An Oxidized Purine Nucleoside Triphosphatase, MTH1, Suppresses Cell Death Caused by Oxidative Stress J. Biol. Chem., September 26, 2003; 278(39): 37965 - 37973. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Sakai, M. Furuichi, M. Takahashi, M. Mishima, S. Iwai, M. Shirakawa, and Y. Nakabeppu A Molecular Basis for the Selective Recognition of 2-Hydroxy-dATP and 8-Oxo-dGTP by Human MTH1 J. Biol. Chem., March 1, 2002; 277(10): 8579 - 8587. [Abstract] [Full Text] [PDF]
|
|