Large kinetic isotope effects in enzymatic proton transfer and the role of substrate oscillations

Dimitri Antoniou, Steven D Schwartz

Research output: Contribution to journalArticle

117 Citations (Scopus)

Abstract

We propose an interpretation of the experimental findings of Klinman and coworkers [Cha, Y., Murray, C. J. and Klinman, J.P. (1989) Science 243, 1325- 1330; Grant, K. L. and Klinman, J.P. (1989) Biochemistry 28, 6597-6605; and Bahnson, B. J. and 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. and 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.

Original languageEnglish (US)
Pages (from-to)12360-12365
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number23
DOIs
StatePublished - Nov 11 1997
Externally publishedYes

Fingerprint

Isotopes
Protons
Biochemistry
Amines
Oxidoreductases
Temperature
Serum

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

@article{0ac9b30b7da24adb8c12089d25694181,
title = "Large kinetic isotope effects in enzymatic proton transfer and the role of substrate oscillations",
abstract = "We propose an interpretation of the experimental findings of Klinman and coworkers [Cha, Y., Murray, C. J. and Klinman, J.P. (1989) Science 243, 1325- 1330; Grant, K. L. and Klinman, J.P. (1989) Biochemistry 28, 6597-6605; and Bahnson, B. J. and 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. and 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.",
author = "Dimitri Antoniou and Schwartz, {Steven D}",
year = "1997",
month = "11",
day = "11",
doi = "10.1073/pnas.94.23.12360",
language = "English (US)",
volume = "94",
pages = "12360--12365",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "23",

}

TY - JOUR

T1 - Large kinetic isotope effects in enzymatic proton transfer and the role of substrate oscillations

AU - Antoniou, Dimitri

AU - Schwartz, Steven D

PY - 1997/11/11

Y1 - 1997/11/11

N2 - We propose an interpretation of the experimental findings of Klinman and coworkers [Cha, Y., Murray, C. J. and Klinman, J.P. (1989) Science 243, 1325- 1330; Grant, K. L. and Klinman, J.P. (1989) Biochemistry 28, 6597-6605; and Bahnson, B. J. and 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. and 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.

AB - We propose an interpretation of the experimental findings of Klinman and coworkers [Cha, Y., Murray, C. J. and Klinman, J.P. (1989) Science 243, 1325- 1330; Grant, K. L. and Klinman, J.P. (1989) Biochemistry 28, 6597-6605; and Bahnson, B. J. and 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. and 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.

UR - http://www.scopus.com/inward/record.url?scp=0030817281&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030817281&partnerID=8YFLogxK

U2 - 10.1073/pnas.94.23.12360

DO - 10.1073/pnas.94.23.12360

M3 - Article

C2 - 9356454

AN - SCOPUS:0030817281

VL - 94

SP - 12360

EP - 12365

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 23

ER -