Meta-Biol

• Pathways

NUDT1 (MTH1) catalyzes the reaction of N6-methyl-ATP and water to form N6-methyl-AMP and PPi (pyrophosphate) (Scaletti et al. 2020). Four NUDT1 proteins have been identified, encoded by a single gene with alternative start codons (Oda et al. 1999). The shortest of these, NUDT1 p18, has been shown to be enzymatically active as a monomer associated with a magnesium ion (Mishima et al. 2004; Sakumi et al. 1993; Takagi et al. 2012). The longer isoforms all consist of the p18 polypeptide with aminoterminal extensions and are presumed to be active as well but have not been experimentally characterized. The p18 isoform is predominantly cytosolic (Kang et al. 1995). While NUDT1 acts less efficiently on N6-methyl-ATP than on N6-methyl-dATP, the intracellular concentration of the latter molecule is likely much greater, consistent with a physiological role for this reaction (Scaletti et al. 2020).