Neutron and time-resolved X-ray crystallography reveal the substrate recognition and catalytic mechanism of human Nudix hydrolase MTH1.

ABSTRACT: Human MTH1, a Nudix enzyme, hydrolyzes several oxidized nucleotides such as 8-oxo-dGTP and 2-oxo-dATP, owing to its broad substrate specificity. MTH1 has also attracted attention as an anticancer target, and its substrate recognition is of biological and medical interest. Previous studies have suggested that MTH1 exhibits broad substrate specificity by changing the protonation states of Asp119 and Asp120 with high pK_a. However, the recognition mechanism remains unclear, owing to the difficulty in directly observing hydrogen atoms. Furthermore, a recent time-resolved X-ray study has proposed that Nudix hydrolases catalyze reactions through a new three-metal-ion mechanism. To understand the substrate recognition and catalytic mechanisms of human MTH1, we performed neutron a

SUBMITTER: Hirata K 

PROVIDER: S-EPMC12305053 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature