Open AccessLarge kinetic isotope effects in enzymatic proton transfer and the role of substrate oscillations
Author(s) -
Dimitri Antoniou,
Steven D. Schwartz
Publication year - 1997
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.94.23.12360
Subject(s) - kinetic isotope effect , excited state , quantum tunnelling , proton , chemistry , substrate (aquarium) , kinetic energy , chemical physics , proton coupled electron transfer , electron transfer , computational chemistry , stereochemistry , atomic physics , physics , condensed matter physics , quantum mechanics , oceanography , deuterium , geology
We propose an interpretation of the experimental findings of Klinman and coworkers [Cha, Y., Murray, C. J. & Klinman, J. P. (1989)Science 243, 1325–1330; Grant, K. L. & Klinman, J. P. (1989)Biochemistry 28, 6597–6605; and Bahnson, B. J. & Klinman, J. P. (1995)Methods Enzymol. 249, 373–397], who showed that proton transfer reactions that are catalyzed by bovine serum amine oxidase proceed through tunneling. We show that two different tunneling models are consistent with the experiments. In the first model, the proton tunnels from the ground state. The temperature dependence of the kinetic isotope effect is caused by a thermally excited substrate mode that modulates the barrier, as has been suggested by Borgis and Hynes [Borgis, D. & Hynes, J. T. (1991)J. Chem. Phys. 94, 3619–3628]. In the second model, there is both over-the-barrier transfer and tunneling from excited states. Finally, we propose two experiments that can distinguish between the possible mechanisms.