Nudix hydrolase 18 (NUDT18)

Nudix hydrolase 18 (NUDT18, also called MTH3) is an enzyme of the Nudix hydrolase family that hydrolyzes oxidatively damaged nucleoside diphosphates, such as 8-oxo-dGDP, 8-oxo-GDP, and other oxidized purine diphosphates, converting them to the corresponding monophosphates. It plays a role in cellular defense by eliminating potentially mutagenic oxidized nucleotides, thereby safeguarding the fidelity of DNA replication and transcription, particularly under conditions of oxidative stress. NUDT18 can also hydrolyze the active triphosphate metabolites of several antiviral drugs (such as remdesivir-TP, ribavirin-TP, and molnupiravir-TP), which may affect the therapeutic efficacy of these agents. The enzyme is structurally related to other MutT homologs (MTH1/NUDT1, MTH2/NUDT15) but has distinct substrate specificity, being most active against oxidized diphosphates rather than triphosphates. While its precise disease role is less defined compared to MTH1, it contributes to cellular homeostasis, DNA integrity, and may have relevance in cancer biology and antiviral drug metabolism.

Other names

MTH3MutT homolog 38-oxo-dGDP phosphatase2-hydroxy-dADP phosphatase7,8-dihydro-8-oxoguanine phosphatasenucleoside diphosphate-linked moiety X motif 18FLJ22494

Hydrolysis of triphosphate metabolites of nucleoside analog antiviral drugs, potentially impacting their pharmacological efficacy. Detoxification of oxidized nucleotide metabolites.