Phosphodiester cleavage in ribonuclease H occurs via an associative two-metal-aided catalytic mechanism.

ABSTRACT: Ribonuclease H (RNase H) belongs to the nucleotidyl-transferase (NT) superfamily and hydrolyzes the phosphodiester linkages that form the backbone of the RNA strand in RNA x DNA hybrids. This enzyme is implicated in replication initiation and DNA topology restoration and represents a very promising target for anti-HIV drug design. Structural information has been provided by high-resolution crystal structures of the complex RNase H/RNA x DNA from Bacillus halodurans (Bh), which reveals that two metal ions are required for formation of a catalytic active complex. Here, we use classical force field-based and quantum mechanics/molecular mechanics calculations for modeling the nucleotidyl transfer reaction in RNase H, clarifying the role of the metal ions and the nature of the nucleophile (wate

SUBMITTER: De Vivo M 

PROVIDER: S-EPMC2745632 | biostudies-literature | 2008 Aug

REPOSITORIES: biostudies-literature