Reaction Mechanism and Metal Selectivity of Human SAMHD1 Elucidated by QM/MM Calculations.

ABSTRACT: 2'-Deoxynucleoside-5'-triphosphate triphosphohydrolases (dNTPases) constitute a crucial enzyme family that plays a pivotal role in antiviral innate immunity. Among these enzymes, human SAMHD1 has emerged as a dNTPase with distinct catalytic properties and active-site architecture. This metalloenzyme regulates cellular dNTP concentration through its ability to hydrolyze all four canonical dNTPs into their corresponding 2'-deoxynucleosides and inorganic triphosphates, a reaction requiring coordinated iron and magnesium ions for enzymatic activity. In the present work, molecular dynamics (MD) simulations and quantum mechanics/molecular mechanics (QM/MM) calculations are employed to investigate the mechanistic details of dATP hydrolysis mediated by two metal ions. Starting from the resolved cr

SUBMITTER: Deng WH 

PROVIDER: S-EPMC12186264 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature