Mechanistic strategies in the HDV ribozyme: chelated and diffuse metal ion interactions and active site protonation.

ABSTRACT: The crystal structure of the precleaved form of the hepatitis delta virus (HDV) ribozyme reveals two G•U wobbles near the active site: a rare reverse G•U wobble involving a syn G base, and a standard G•U wobble at the cleavage site. The catalytic mechanism for this ribozyme has been proposed to involve a Mg(2+) ion bound to the reverse G•U wobble, as well as a protonated C75 base. We carried out molecular dynamics simulations to analyze metal ion interaction with the reverse and standard G•U wobbles and to investigate the impact of C75 protonation on the structure and motions of the ribozyme. We identified two types of Mg(2+) ions associated with the ribozyme, chelated and diffuse, at the reverse and standard G•U wobbles, respectively, which appear to contribute to catalysis and stability,

SUBMITTER: Veeraraghavan N 

PROVIDER: S-EPMC3144556 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature