title: Enzyme mechanisms from molecular modeling and isotope effects.
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.
authors.affiliation: Institute of Applied Radiation Chemistry, Technical University of Lodz, Zeromskiego 116, 90-924 Lodz, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Dybala-Defratyka
authors.forename: Michal
authors.initials: M
authors.lastname: Rostkowski
authors.forename: Piotr
authors.initials: P
authors.lastname: Paneth
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D003903:Deuterium; D005656:Fungal Proteins / Q000737:chemistry*; D006867:Hydrolases / Q000737:chemistry*; D007536:Isomerism; D007700:Kinetics; D008765:Methylmalonyl-CoA Mutase / Q000737:chemistry*; D008954:Models, Biological; D008958:Models, Molecular; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D005656:Fungal Proteins; D003903:Deuterium; C086024:tetrahydroxynaphthalene reductase; D044925:Oxidoreductases Acting on CH-CH Group Donors; D006867:Hydrolases; C034507:2-haloacid dehalogenase; D008765:Methylmalonyl-CoA Mutase