tailieunhanh - Báo cáo Y học: Environmentally coupled hydrogen tunneling Linking catalysis to dynamics

Many biological C-H activation reactions exhibit nonclassical kinetic isotope effects (KIEs). These nonclassical KIEs are too large (kH/kD 7) and/or exhibit unusual temperature dependence such that the Arrhenius prefactor KIEs (AH/AD) fall outside of the semiclassical range near unity. The focus of this minireview is to discuss such KIEs within the context of the environmentally coupled hydrogen tunneling model. Full tunneling models of hydrogen transfer assume that protein or solvent fluctuations generate a reactive configuration along the classical, heavy-atom coordinate, from which the hydrogen transfers via nuclear tunneling. Environmentally coupled tunneling also invokes an environmental vibration (gating) that modulates. | Eur. J. Biochem. 269 3113-3121 2002 FEBS 2002 doi MINIREVIEW Environmentally coupled hydrogen tunneling Linking catalysis to dynamics Michael J. Knapp1 and Judith P. Klinman1 2 1 Department of Chemistry and department of Molecular and Cell Biology University of California Berkeley USA Many biological C-H activation reactions exhibit nonclas-sical kinetic isotope effects KIEs . These nonclassical KIEs are too large kH kD 7 and or exhibit unusual temperature dependence such that the Arrhenius prefactor KIEs Ah Ad fall outside of the semiclassical range near unity. The focus of this minireview is to discuss such KIEs within the context of the environmentally coupled hydrogen tunneling model. Full tunneling models of hydrogen transfer assume that protein or solvent fluctuations generate a reactive configuration along the classical heavy-atom coordinate from which the hydrogen transfers via nuclear tunneling. Environmentally coupled tunneling also invokes an environmental vibration gating that modulates the tunneling barrier leading to a temperature-dependent KIE. These properties directly link enzyme fluctuations to the reaction coordinate for hydrogen transfer making a quantum view of hydrogen transfer necessarily a dynamic view of catalysis. The environmentally coupled hydrogen tunneling model leads to a range of magnitudes of KIEs which reflect the tunneling barrier and a range of AH AD values which reflect the extent to which gating modulates hydrogen transfer. Gating is the primary determinant of the temperature dependence of the KIE within this model providing insight into the importance of this motion in modulating the reaction coordinate. The potential use of variable temperature KIEs as a direct probe of coupling between environmental dynamics and the reaction coordinate is described. The evolution from application of a tunneling correction to a full tunneling model in enzymatic H transfer reactions is discussed in the context