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.