7,8-dihydro-8-oxoguanine triphosphatase; 8-oxo-dGTPase; nucleoside diphosphate-linked moiety X motif 1; Nudix motif 1 (NUDT1, MTH1)
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Function
- anti-mutagenic
- prevent misincorporation of 8-oxo-dGTP into DNA thus preventing A:T to C:G transversions
8-oxo-dGTP + H2O <--> 8-oxo-dGMP + diphosphate
Structure
- N-terminus is blocked
- belongs to the Nudix hydrolase family
Expression
- widely expressed
- highest expression in thymus, testis, embryo & proliferating blood lymphocytes
- in peripheral blood lymphocytes, expressed at much higher levels in proliferating cells than in resting cells
Pathology
Polymorphism
- a polymorphism between Met-1 & Met-19 removes a stop codon before the initiation codon for isoform p22 & gives rise to the production of isoform p26
- the allele frequency of isoform p26 is about 20%
Pharmacology
- (S)-crizotinib inhibits MTH1[2]
More general terms
References
- ↑ UniProt http://www.uniprot.org/uniprot/P36639.html
- ↑ 2.0 2.1 2.2 Gad H et al. MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool. Nature 2014 Apr 10; 508:215. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24695224 <Internet> http://www.nature.com/nature/journal/v508/n7495/full/nature13181.html
Huber KVM et al. Stereospecific targeting of MTH1 by (S)-crizotinib as an anticancer strategy. Nature 2014 Apr 10; 508:222. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24695225 <Internet> http://www.nature.com/nature/journal/v508/n7495/full/nature13194.html
Dominissini D and He C. Damage prevention targeted. Nature 2014 Apr 10; 508:191 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24695227 <Internet> http://www.nature.com/nature/journal/v508/n7495/full/nature13221.html