Enzyme mechanisms from molecular modeling and isotope effects

Arch Biochem Biophys. 2008 Jun 15;474(2):274-82. doi: 10.1016/j.abb.2008.01.012. Epub 2008 Jan 24.

Abstract

The application of kinetic isotope effects and molecular modeling to characterize three enzyme-catalyzed reactions is presented; the mechanism of the chloroacid dehalogenase catalyzed reaction is approached using chlorine kinetic isotope effects and solvent kinetic isotope effects. The pre-steady-state phase of the reaction catalyzed by methylmalonyl-CoA mutase is approached by different QM/MM schemes and the results are validated by comparison with the experimental value of the deuterium kinetic isotope effect. Finally, a procedure for improving QM/MM calculations is illustrated by analysis of the trihydroxynaphthalene reductase-catalyzed reaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Computer Simulation
  • Deuterium
  • Fungal Proteins / chemistry*
  • Hydrolases / chemistry*
  • Isomerism
  • Kinetics
  • Methylmalonyl-CoA Mutase / chemistry*
  • Models, Biological*
  • Models, Molecular*
  • Oxidoreductases Acting on CH-CH Group Donors / chemistry*
  • Thermodynamics

Substances

  • Fungal Proteins
  • Deuterium
  • tetrahydroxynaphthalene reductase
  • Oxidoreductases Acting on CH-CH Group Donors
  • Hydrolases
  • 2-haloacid dehalogenase
  • Methylmalonyl-CoA Mutase