title: QM/MM determination of kinetic isotope effects for COMT-catalyzed methyl transfer does not support compression hypothesis.
abstract: 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.
authors.affiliation: Department of Chemistry, University of Bath, BA2 7AY Bath, UK.
authors.forename: Giuseppe D
authors.initials: GD
authors.lastname: Ruggiero
authors.forename: Ian H
authors.initials: IH
authors.lastname: Williams
authors.forename: Maite
authors.initials: M
authors.lastname: Roca
authors.forename: Vicent
authors.initials: V
authors.lastname: Moliner
authors.forename: Iñaki
authors.initials: I
authors.lastname: Tuñón
mesh_terms: D002247:Carbon Isotopes / Q000737:chemistry*; D002384:Catalysis; D002394:Catechol O-Methyltransferase / Q000737:chemistry*; D003198:Computer Simulation; D007700:Kinetics; D008745:Methylation; D008956:Models, Chemical; D015394:Molecular Structure; D010084:Oxidation-Reduction; D011789:Quantum Theory
chemical_list: D002247:Carbon Isotopes; D002394:Catechol O-Methyltransferase