Origin of mutational effects at the C3 and G8 positions on hammerhead ribozyme catalysis from molecular dynamics simulations

J Am Chem Soc. 2008 Jun 11;130(23):7168-9. doi: 10.1021/ja711242b. Epub 2008 May 14.

Abstract

A series of ten 60 ns molecular dynamics (MD) simulations of the native and mutated full length hammerhead ribozymes in the reactant state and in an activated precursor state (G8:2'OH deprotonated) are reported. Mutant simulations include the C3U, G8A, and G8I single mutants and a C3U/G8A double mutant that exhibits an experimental rescue effect. The results provide critical details into the origin of the observed mutation effects and support a mechanism where the 2'OH of G8 acts as a general acid catalyst that is held in position through Watson-Crick hydrogen bonding between G8 and C3.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Catalysis
  • Computer Simulation
  • Hydrogen Bonding
  • Kinetics
  • Magnesium / chemistry
  • Magnesium / metabolism
  • Mutation
  • RNA, Catalytic / chemistry*
  • RNA, Catalytic / genetics
  • RNA, Catalytic / metabolism*
  • Static Electricity
  • Structure-Activity Relationship
  • Water / chemistry

Substances

  • RNA, Catalytic
  • hammerhead ribozyme
  • Water
  • Magnesium