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

研究成果: Contribution to journalArticle

7 引用 (Scopus)

抜粋

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.

元の言語英語
ページ(範囲)843-849
ページ数7
ジャーナルJournal of biochemistry
140
発行部数6
DOI
出版物ステータス出版済み - 12 1 2006

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

フィンガープリント Recognition of nucleotide analogs containing the 7,8-dihydro-8-oxo structure by the human MTH1 protein' の研究トピックを掘り下げます。これらはともに一意のフィンガープリントを構成します。

  • これを引用

    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, 140(6), 843-849. https://doi.org/10.1093/jb/mvj214