PR01403

8OXTPHPHTASE

PRINTS entry
Member databasePRINTS
PRINTS typefamily
Short name8OXTPHPHTASE

Description
Imported from IPR003563

This entry represents Oxidized purine nucleoside triphosphate hydrolase (8ODP, also known as 7,8-dihydro-8-oxoguanine triphosphatase and MHT1), and similar Nudix hydrolase domain-containing proteins from bacteria, eukaryots and archaea. This protein has a significant hydrolase activity toward 2-oxo-ATP, 8-oxo-dGTP and 8-oxo-dATP and catalyzes the hydrolysis of methylated purine nucleoside triphosphate preventing their integration into DNA
[5, 6, 1]
. It was originally considered to play an important role as sanitizer of the oxidized nucleotide pool
[1, 4]
. However, later studies indicate that NUDT1 plays a redundant role in eliminating oxidized nucleotides and that it is not essential for cancer cell proliferation and survival
[2, 3]
.

References
Imported from IPR003563

1.cDNA and genomic sequences for rat 8-oxo-dGTPase that prevents occurrence of spontaneous mutations due to oxidation of guanine nucleotides. Cai JP, Kakuma T, Tsuzuki T, Sekiguchi M. Carcinogenesis 16, 2343-50, (1995). View articlePMID: 7586133

2.Novel Class of Potent and Cellularly Active Inhibitors Devalidates MTH1 as Broad-Spectrum Cancer Target. Ellermann M, Eheim A, Rahm F, Viklund J, Guenther J, Andersson M, Ericsson U, Forsblom R, Ginman T, Lindstrom J, Silvander C, Tresaugues L, Giese A, Bunse S, Neuhaus R, Weiske J, Quanz M, Glasauer A, Nowak-Reppel K, Bader B, Irlbacher H, Meyer H, Queisser N, Bauser M, Haegebarth A, Gorjanacz M. ACS Chem Biol 12, 1986-1992, (2017). PMID: 28679043

3.Proteomic profiling of small-molecule inhibitors reveals dispensability of MTH1 for cancer cell survival. Kawamura T, Kawatani M, Muroi M, Kondoh Y, Futamura Y, Aono H, Tanaka M, Honda K, Osada H. Sci Rep 6, 26521, (2016). PMID: 27210421

4.MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool. Gad H, Koolmeister T, Jemth AS, Eshtad S, Jacques SA, Strom CE, Svensson LM, Schultz N, Lundback T, Einarsdottir BO, Saleh A, Gokturk C, Baranczewski P, Svensson R, Berntsson RP, Gustafsson R, Stromberg K, Sanjiv K, Jacques-Cordonnier MC, Desroses M, Gustavsson AL, Olofsson R, Johansson F, Homan EJ, Loseva O, Brautigam L, Johansson L, Hoglund A, Hagenkort A, Pham T, Altun M, Gaugaz FZ, Vikingsson S, Evers B, Henriksson M, Vallin KS, Wallner OA, Hammarstrom LG, Wiita E, Almlof I, Kalderen C, Axelsson H, Djureinovic T, Puigvert JC, Haggblad M, Jeppsson F, Martens U, Lundin C, Lundgren B, Granelli I, Jensen AJ, Artursson P, Nilsson JA, Stenmark P, Scobie M, Berglund UW, Helleday T. Nature 508, 215-21, (2014). PMID: 24695224

5.MutT homologue 1 (MTH1) catalyzes the hydrolysis of mutagenic O6-methyl-dGTP. Jemth AS, Gustafsson R, Brautigam L, Henriksson L, Vallin KSA, Sarno A, Almlof I, Homan E, Rasti A, Warpman Berglund U, Stenmark P, Helleday T. Nucleic Acids Res 46, 10888-10904, (2018). PMID: 30304478

6.MutT homologue 1 (MTH1) removes N6-methyl-dATP from the dNTP pool. Scaletti ER, Vallin KS, Brautigam L, Sarno A, Warpman Berglund U, Helleday T, Stenmark P, Jemth AS. J Biol Chem 295, 4761-4772, (2020). PMID: 32144205

Supplementary References

1. Cloning and expression of cDNA for a human enzyme that hydrolyzes 8-oxo-dGTP, a mutagenic substrate for DNA synthesis. Sakumi K, Furuichi M, Tsuzuki T, Kakuma T, Kawabata S, Maki H, Sekiguchi M. J. Biol. Chem. 268, 23524-30, (1993). View articlePMID: 8226881

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