Premium
Solvent Effects on Environmentally Coupled Hydrogen Tunnelling During Catalysis by Dihydrofolate Reductase from Thermotoga maritima
Author(s) -
Loveridge E. Joel,
Evans Rhian M.,
Allemann Rudolf K.
Publication year - 2008
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200801804
Subject(s) - thermotoga maritima , kinetic isotope effect , hydride , quantum tunnelling , chemistry , reaction rate constant , viscosity , dihydrofolate reductase , chemical physics , dielectric , thermodynamics , hydrogen , kinetics , deuterium , atomic physics , physics , condensed matter physics , classical mechanics , organic chemistry , quantum mechanics , enzyme , biochemistry , escherichia coli , gene
Protein motions may be perturbed by altering the properties of the reaction medium. Here we show that dielectric constant, but not viscosity, affects the rate of the hydride‐transfer reaction catalysed by dihydrofolate reductase from Thermotoga maritima (TmDHFR), in which quantum‐mechanical tunnelling has previously been shown to be driven by protein motions. Neither dielectric constant nor viscosity directly alters the kinetic isotope effect of the reaction or the mechanism of coupling of protein motions to tunnelling. Glycerol and sucrose cause a significant increase in the rate of hydride transfer, but lead to a reduction in the magnitude of the kinetic isotope effect as well as an extension of the temperature range over which “passive” protein dynamics (rather than “active” gating motions) dominate the reaction. Our results are in agreement with the proposal that non‐equilibrium dynamical processes (promoting motions) drive the hydride‐transfer reaction in TmDHFR.