Linking protein structure and dynamics to catalysis: the role of hydrogen tunnelling.
Early studies of enzyme-catalysed hydride transfer reactions indicated kinetic anomalies that were initially interpreted in the context of a 'tunnelling correction'. An alternate model for tunnelling emerged following studies of the hydrogen atom transfer catalysed by the enzyme soybean lipoxygenase. This invokes full tunnelling of all isotopes of hydrogen, with reaction barriers reflecting the heavy atom, environmental reorganization terms. Using the latter approach, we offer an integration of the aggregate data implicating hydrogen tunnelling in enzymes (i.e. deviations from Swain-Schaad relationships and the semi-classical temperature dependence of the hydrogen isotope effect). The impact of site-specific mutations of enzymes plays a critical role in our understanding of the factors that control tunnelling in enzyme reactions.
Klinman
Judith P
JP
Department of Chemistry, University of California, Berkeley, CA 94720-1460, USA. klinman@berkeley.edu
D000426:Alcohol Dehydrogenase / Q000378:metabolism; D001665:Binding Sites / Q000235:genetics; D002384:Catalysis; D004798:Enzymes / Q000235:genetics* / Q000378:metabolism*; D006859:Hydrogen / Q000378:metabolism*; D007700:Kinetics; D008956:Models, Chemical; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D011487:Protein Conformation; D013696:Temperature
D004798:Enzymes; D006859:Hydrogen; D000426:Alcohol Dehydrogenase