Journal article
Hydrogen donor-acceptor fluctuations from kinetic isotope effects: a phenomenological model
Biochemistry (Easton), Vol.51(34), pp.6860-6870
08/28/2012
DOI: 10.1021/bi300613e
PMCID: PMC3448806
PMID: 22857146
Abstract
Kinetic isotope effects (KIEs) and their temperature dependence can probe the structural and dynamic nature of enzyme-catalyzed proton or hydride transfers. The molecular interpretation of their temperature dependence requires expensive and specialized quantum mechanics/molecular mechanics (QM/MM) calculations to provide a quantitative molecular understanding. Currently available phenomenological models use a nonadiabatic assumption that is not appropriate for most hydride and proton-transfer reactions, while others require more parameters than the experimental data justify. Here we propose a phenomenological interpretation of KIEs based on a simple method to quantitatively link the size and temperature dependence of KIEs to a conformational distribution of the catalyzed reaction. This model assumes adiabatic hydrogen tunneling, and by fitting experimental KIE data, the model yields a population distribution for fluctuations of the distance between donor and acceptor atoms. Fits to data from a variety of proton and hydride transfers catalyzed by enzymes and their mutants, as well as nonenzymatic reactions, reveal that steeply temperature-dependent KIEs indicate the presence of at least two distinct conformational populations, each with different kinetic behaviors. We present the results of these calculations for several published cases and discuss how the predictions of the calculations might be experimentally tested. This analysis does not replace molecular QM/MM investigations, but it provides a fast and accessible way to quantitatively interpret KIEs in the context of a Marcus-like model.
Details
- Title: Subtitle
- Hydrogen donor-acceptor fluctuations from kinetic isotope effects: a phenomenological model
- Creators
- Daniel Roston - Department of Chemistry, University of Iowa, Iowa City, IA 52242, USAChristopher M CheatumAmnon Kohen
- Resource Type
- Journal article
- Publication Details
- Biochemistry (Easton), Vol.51(34), pp.6860-6870
- DOI
- 10.1021/bi300613e
- PMID
- 22857146
- PMCID
- PMC3448806
- NLM abbreviation
- Biochemistry
- ISSN
- 1520-4995
- eISSN
- 1520-4995
- Publisher
- United States
- Grant note
- R01 GM65368 / NIGMS NIH HHS T32 GM008365 / NIGMS NIH HHS R01 GM065368 / NIGMS NIH HHS
- Language
- English
- Date published
- 08/28/2012
- Academic Unit
- Core Research Facilities; Chemistry
- Record Identifier
- 9983985823102771
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