Controlled Trafficking of Multiple and Diverse Cations Prompts Nucleic Acid Hydrolysis.

ABSTRACT: Recent in crystallo reaction intermediates have detailed how nucleic acid hydrolysis occurs in the RNA ribonuclease H1 (RNase H1), a fundamental metalloenzyme involved in maintaining the human genome. At odds with the previous characterization, these in crystallo structures unexpectedly captured multiple metal ions (K⁺ and Mg²⁺) transiently bound in the vicinity of the two-metal-ion active site. Using multi-microsecond all-atom molecular dynamics and free-energy simulations, we investigated the functional implications of the dynamic exchange of multiple K⁺ and Mg²⁺ ions at the RNase H1 reaction center. We found that such ions are timely positioned at non-overlapping locations near the active site, at different stages of catalysis, b

SUBMITTER: Manigrasso J 

PROVIDER: S-EPMC8827413 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature