Recognition of nucleotide analogs containing the 7,8-dihydro-8-oxo structure by the human MTH1 protein

Hiroyuki Kamiya, Claudio Cadena-Amaro, Laurence Dugué, Hiroyuki Yakushiji, Noriaki Minakawa, Akira Matsuda, Sylvie Pochet, Yusaku Nakabeppu, Hideyoshi Harashima

Research output: Contribution to journalArticle

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Abstract

The MTH1 protein catalyzes hydrolysis of oxidatively damaged purine nucleotides including 8-hydroxy-dGTP to the monophosphates. The MTH1 protein seems to act as an important defense system against mutagenesis, carcinogenesis, and cell death induced by oxidized purine nucleotides. We previously reported that the functional groups at the 2- and 6-positions of the purine ring affect the recognition by the human MTH1 protein. 8-Hydroxy-dGTP and 8-hydroxy-dATP are substrates of MTH1, and both have the "7,8-dihydro-8-oxo structure." In this study, three nucleotide analogs containing this motif were examined. A synthetic purine analog containing the 7,8-dihydro-8-oxo structure and the 2-amino function (dJTP) was hydrolyzed to the monophosphate with high efficiency by MTH1. On the other hand, two analogs that lack the two-ring system of their bases [formamidopyrimidine-dGTP (FAPY-dGTP) and 2-OH-dYTP] were poor substrates. FAPY-dGTP is a mixture of conformers and was hydrolyzed more than ten-fold less efficiently than 8-hydroxy-dGTP. These results clarify the effects of the 2-amino group and the two-ring system of the purine base on the recognition by the human MTH1 protein.

Original languageEnglish
Pages (from-to)843-849
Number of pages7
JournalJournal of biochemistry
Volume140
Issue number6
DOIs
Publication statusPublished - Dec 1 2006

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Purine Nucleotides
Nucleotides
Mutagenesis
Cell death
Substrates
Functional groups
Hydrolysis
Carcinogenesis
Proteins
Cell Death
8-oxodGTPase
purine
8-hydroxy-dGTP
deoxyguanosine triphosphate
hydroxide ion
1-(2-deoxyribofuranosyl)-2,3-dihydro-2-oxoimidazole-4-carboxamide 5'-triphosphate

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

Cite this

Kamiya, H., Cadena-Amaro, C., Dugué, L., Yakushiji, H., Minakawa, N., Matsuda, A., ... Harashima, H. (2006). Recognition of nucleotide analogs containing the 7,8-dihydro-8-oxo structure by the human MTH1 protein. Journal of biochemistry, 140(6), 843-849. https://doi.org/10.1093/jb/mvj214

Recognition of nucleotide analogs containing the 7,8-dihydro-8-oxo structure by the human MTH1 protein. / Kamiya, Hiroyuki; Cadena-Amaro, Claudio; Dugué, Laurence; Yakushiji, Hiroyuki; Minakawa, Noriaki; Matsuda, Akira; Pochet, Sylvie; Nakabeppu, Yusaku; Harashima, Hideyoshi.

In: Journal of biochemistry, Vol. 140, No. 6, 01.12.2006, p. 843-849.

Research output: Contribution to journalArticle

Kamiya, H, Cadena-Amaro, C, Dugué, L, Yakushiji, H, Minakawa, N, Matsuda, A, Pochet, S, Nakabeppu, Y & Harashima, H 2006, 'Recognition of nucleotide analogs containing the 7,8-dihydro-8-oxo structure by the human MTH1 protein', Journal of biochemistry, vol. 140, no. 6, pp. 843-849. https://doi.org/10.1093/jb/mvj214
Kamiya H, Cadena-Amaro C, Dugué L, Yakushiji H, Minakawa N, Matsuda A et al. Recognition of nucleotide analogs containing the 7,8-dihydro-8-oxo structure by the human MTH1 protein. Journal of biochemistry. 2006 Dec 1;140(6):843-849. https://doi.org/10.1093/jb/mvj214
Kamiya, Hiroyuki ; Cadena-Amaro, Claudio ; Dugué, Laurence ; Yakushiji, Hiroyuki ; Minakawa, Noriaki ; Matsuda, Akira ; Pochet, Sylvie ; Nakabeppu, Yusaku ; Harashima, Hideyoshi. / Recognition of nucleotide analogs containing the 7,8-dihydro-8-oxo structure by the human MTH1 protein. In: Journal of biochemistry. 2006 ; Vol. 140, No. 6. pp. 843-849.
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