title: Coupling of hydrogenic tunneling to active-site motion in the hydrogen radical transfer catalyzed by a coenzyme B12-dependent mutase.
abstract: Hydrogen transfer reactions catalyzed by coenzyme B(12)-dependent methylmalonyl-CoA mutase have very large kinetic isotope effects, indicating that they proceed by a highly quantal tunneling mechanism. We explain the kinetic isotope effect by using a combined quantum mechanical/molecular mechanical potential and semiclassical quantum dynamics calculations. Multidimensional tunneling increases the magnitude of the calculated intrinsic hydrogen kinetic isotope effect by a factor of 3.6 from 14 to 51, in excellent agreement with experimental results. These calculations confirm that tunneling contributions can be large enough to explain even a kinetic isotope effect >50, not because the barrier is unusually thin but because corner-cutting tunneling decreases the distance over which the system tunnels without a comparable increase in either the effective potential barrier or the effective mass for tunneling.
authors.affiliation: Institute of Applied Radiation Chemistry, Department of Chemistry, Technical University of Lodz, Zeromskiego 116, 90-924 Lodz, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Dybala-Defratyka
authors.forename: Piotr
authors.initials: P
authors.lastname: Paneth
authors.forename: Ruma
authors.initials: R
authors.lastname: Banerjee
authors.forename: Donald G
authors.initials: DG
authors.lastname: Truhlar
mesh_terms: D001665:Binding Sites; D002384:Catalysis; D003038:Cobamides / Q000737:chemistry*; D003903:Deuterium; D005609:Free Radicals / Q000737:chemistry*; D006859:Hydrogen / Q000737:chemistry*; D019751:Intramolecular Transferases / Q000737:chemistry*; D007700:Kinetics; D008956:Models, Chemical; D008958:Models, Molecular; D009038:Motion; D011789:Quantum Theory; D014805:Vitamin B 12
chemical_list: D003038:Cobamides; D005609:Free Radicals; D006859:Hydrogen; D003903:Deuterium; D019751:Intramolecular Transferases; C000913:cobamamide; D014805:Vitamin B 12