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Enzymatic catalysis and transfers in solution. I. Theory and computations, a unified view

Marcus, R. A. (2006) Enzymatic catalysis and transfers in solution. I. Theory and computations, a unified view. Journal of Chemical Physics, 125 (19). Art. No. 194504. ISSN 0021-9606. doi:10.1063/1.2372496.

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The transfer of hydride, proton, or H atom between substrate and cofactor in enzymes has been extensively studied for many systems, both experimentally and computationally. A simple equation for the reaction rate, an analog of an equation obtained earlier for electron transfer rates, is obtained, but now containing an approximate analytic expression for the bond rupture-bond forming feature of these H transfers. A "symmetrization," of the potential energy surfaces is again introduced [R. A. Marcus, J. Chem. Phys. 43, 679 (1965); J. Phys. Chem. 72, 891 (1968)], together with Gaussian fluctuations of the remaining coordinates of the enzyme and solution needed for reaching the transition state. Combining the two expressions for the changes in the difference of the two bond lengths of the substrate-cofactor subsystem and in the fluctuation coordinates of the protein leading to the transition state, an expression is obtained for the free energy barrier. To this end a two-dimensional reaction space (m,n) is used that contains the relative coordinates of the H in the reactants, the heavy atoms to which it is bonded, and the protein/solution reorganization coordinate, all leading to the transition state. The resulting expression may serve to characterize in terms of specific parameters (two "reorganization" terms, thermodynamics, and work terms), experimental and computational data for different enzymes, and different cofactor-substrate systems. A related characterization was used for electron transfers. To isolate these factors from nuclear tunneling, when the H-tunneling effect is large, use of deuterium and tritium transfers is of course helpful, although tunneling has frequently and understandably dominated the discussions. A functional form is suggested for the dependence of the deuterium kinetic isotope effect (KIE) on DeltaG° and a different form for the 13C KIE. Pressure effects on deuterium and 13C KIEs are also discussed. Although formulated for a one-step transfer of a light particle in an enzyme, the results would also apply to single-step transfers of other atoms and groups in enzymes and in solution.

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Marcus, R. A.0000-0001-6547-1469
Additional Information:©2006 American Institute of Physics (Received 23 August 2006; accepted 2 October 2006; published online 15 November 2006) It is a pleasure to acknowledge the support of this research by the Office of Naval Research and the National Science Foundation and to acknowledge helpful discussions with Arieh Warshel, Amnon Kohen, Sharon Hammes-Schiffer, Don Truhlar, Jiali Gao, Judith Klinman, and Maria Michel-Beyerle.
Subject Keywords:enzymes; molecular biophysics; catalysis; biochemistry; chemical exchanges; reaction kinetics theory; charge exchange; bond lengths; potential energy surfaces; free energy; isotope effects; fluctuations
Issue or Number:19
Record Number:CaltechAUTHORS:MARjcp06b
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:6415
Deposited By: Archive Administrator
Deposited On:07 Dec 2006
Last Modified:08 Nov 2021 20:33

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