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RESEARCH PRODUCT
QM/MM Determination of Kinetic Isotope Effects for COMT-Catalyzed Methyl Transfer Does Not Support Compression Hypothesis
Vicent MolinerIan H. WilliamsMaite RocaIñaki TuñónGiuseppe D. Ruggierosubject
Carbon IsotopesCatecholAqueous solutionMolecular StructureStereochemistryGeneral ChemistryCatechol O-MethyltransferaseMethylationBiochemistryCatalysisCatalysisIonEnzyme catalysisQM/MMKineticschemistry.chemical_compoundColloid and Surface ChemistryModels ChemicalchemistryKinetic isotope effectQuantum TheoryPhysical chemistryComputer SimulationOxidation-ReductionMethyl groupdescription
Secondary alpha-D3 kinetic isotope effects calculated by the hybrid AM1/TIP3P/CHARMM method for the reaction of S-adenosylmethionine with catecholate anion in aqueous solution and catalyzed by rat liver catechol O-methyltransferase at 298 K are 0.94 and 0.85, respectively, in good accord with experiment. The large inverse effect for the enzymatic reaction is not due to compression but arises from significant increases in the stretching and bending force constants involving the isotopically substituted atoms of the transferring methyl group as between the reactant complex and the transition structure, larger than for the reaction in water.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2004-06-22 | Journal of the American Chemical Society |