Substrate recognition by the human MTH1 protein.
A nucleotide pool sanitizing enzyme, the human MTH1 protein, hydrolyzes 2-hydroxy-dATP, 8-hydroxy-dATP, and 8-hydroxyd-GTP. To examine the substrate recognition mechanism of the MTH1 protein, ten nucleotide analogs (8-bromo-dATP, 8-bromod-GTP, deoxyisoinosine triphosphate, 8-hydroxy-dITP, 2-aminopurine-deoxyriboside triphosphate, 2-amino-dATP, deoxyxanthosine triphosphate, deoxyoxanosine triphosphate, dITP, and dUTP) were incubated with the protein. Of these, the former five nucleotides were hydrolyzed with various efficiencies. This results suggests the importance of the anti/syn-conformation and the functional groups on the 2 and 6-positions of the purine ring.
Kamiya
Hiroyuki
H
Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
Dugué
Laurence
L
Yakushiji
Hiroyuki
H
Pochet
Sylvie
S
Nakabeppu
Yusaku
Y
Harashima
Hideyoshi
H
D045643:DNA Repair Enzymes; D006801:Humans; D009711:Nucleotides / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D013379:Substrate Specificity
D009711:Nucleotides; D010744:Phosphoric Monoester Hydrolases; C078207:8-oxodGTPase; D045643:DNA Repair Enzymes