Human MTH1 protein hydrolyzes the oxidized ribonucleotide, 2-hydroxy-ATP

Katsuyoshi Fujikawa, Hiroyuki Kamiya, Hiroyuki Yakushiji, Yusaku Nakabeppu, Hiroshi Kasai

Research output: Contribution to journalArticlepeer-review

98 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)449-454
Number of pages6
JournalNucleic acids research
Volume29
Issue number2
DOIs
Publication statusPublished - Jan 15 2001

All Science Journal Classification (ASJC) codes

  • Genetics

Fingerprint Dive into the research topics of 'Human MTH1 protein hydrolyzes the oxidized ribonucleotide, 2-hydroxy-ATP'. Together they form a unique fingerprint.

Cite this