Thio effects and an unconventional metal ion rescue in the genomic hepatitis delta virus ribozyme.

ABSTRACT: Metal ion and nucleobase catalysis are important for ribozyme mechanism, but the extent to which they cooperate is unclear. A crystal structure of the hepatitis delta virus (HDV) ribozyme suggested that the pro-RP oxygen at the scissile phosphate directly coordinates a catalytic Mg(2+) ion and is within hydrogen bonding distance of the amine of the general acid C75. Prior studies of the genomic HDV ribozyme, however, showed neither a thio effect nor metal ion rescue using Mn(2+). Here, we combine experiment and theory to explore phosphorothioate substitutions at the scissile phosphate. We report significant thio effects at the scissile phosphate and metal ion rescue with Cd(2+). Reaction profiles with an SP-phosphorothioate substitution are indistinguishable from those of the unmodified su

SUBMITTER: Thaplyal P 

PROVIDER: S-EPMC3825741 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature