Nucleic Acids Research, Vol 25, Issue 17 3421-3427, Copyright © 1997 by Oxford University Press
T Hermann, P Auffinger, WG Scott and E Westhof
In the presence of magnesium ions, cleavage by the hammerhead ribozyme RNA
at a specific residue leads to 2'3'-cyclic phosphate and 5'-OH extremities.
In the cleavage reaction an activated ribose 2'-hydroxyl group attacks its
attached 3'-phosphate. Molecular dynamics simulations of the crystal
structure of the hammerhead ribozyme, obtained after flash-freezing of
crystals under conditions where the ribozyme is active, provide evidence
that a mu-bridging OH-ion is located between two Mg2+ions close to the
cleavable phosphate. Constrained simulations show further that a flip from
the C3'- endo to the C2'- endo conformation of the ribose at the cleavable
phosphate brings the 2'- hydroxyl in proximity to both the attacked
phosphorous atom and the mu- bridging OH-ion. Thus, the simulations lead to
a detailed new insight into the mechanism of hammerhead ribozyme cleavage
where a mu-hydroxo bridged magnesium cluster, located on the deep groove
side, provides an OH-ion that is able to activate the 2'-hydroxyl
nucleophile after a minor and localized conformational change in the RNA.
ARTICLES
Evidence for a hydroxide ion bridging two magnesium ions at the active site of the hammerhead ribozyme
Institut de Biologie Moleculaire et Cellulaire du CNRS, 15 rue Rene Descartes, F-67084 Strasbourg, France.
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