An experimentally based family of potential energy surfaces for hydride transfer between NAD+ analogs

Kim, Yong-Ho; Truhlar, Donald G.; Kreevoy, Maurice M.

doi:10.1021/ja00021a002

Cited by 100 publications

(136 citation statements)

References 2 publications

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“…For computational simplicity, therefore, we base our calculations on the hypothetical symmetric transfer of H − from reduced to oxidized nicotinamide moieties, in a manner similar to a model for symmetric H-transfer in solution. 53 The donor and acceptor moieties are analogous to the ubiquitous nicotinamide biological cofactor NAD(P) + . A hydrogen truncates the nicotinamide rings where they normally link to the ribosyl moiety of NAD(P) + , so the system contains a total of 33 atoms (Figure 3) and an overall charge of +1.…”

Section: Methodsmentioning

confidence: 99%

Hydrogen Donor–Acceptor Fluctuations from Kinetic Isotope Effects: A Phenomenological Model

2012

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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 QM/MM calculations to provide a quantitative molecular understanding. Currently available phenomenological models use a non-adiabatic 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. The present 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 non-enzymatic 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. The current analysis does not replace molecular quantum mechanics/molecular mechanics (QM/MM) investigations, but it provides a fast and accessible way to quantitatively interpret KIEs in the context of a Marcus-like model.

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Section: Methodsmentioning

confidence: 99%

Hydrogen Donor–Acceptor Fluctuations from Kinetic Isotope Effects: A Phenomenological Model

2012

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“…93 In many respects, this theory is similar to TST with a transmission coefficient based on large-curvature tunneling. 147,236,[260][261][262][346][347][348][349][350][351][352][353] In both cases, the TST rate constant is multiplied by a factor that reflects the "interplay between donor-acceptor configuration and nuclear tunneling". Their general expression for the transition probability takes account of all possible paths averaged over energy 305,307 and in this respect is similar to the large-curvature tunneling coefficient that involves, 260,347,[351][352][353][354] for each energy, a convolution of the probability of a given nuclear configuration and the tunneling probability at that configuration, followed by a Boltzmann average over energies.…”

Section: Modelsmentioning

confidence: 99%

Multidimensional Tunneling, Recrossing, and the Transmission Coefficient for Enzymatic Reactions

2006

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“…The first factor f 1 is assumed to arise from protein dynamics, and it is sometimes assumed to be independent of m ; this first factor is the free energy to bring the donor and acceptor into a tunneling‐ready configuration. That concept is reminiscent of the “work term” in Marcus theory 35, 81, 84, 85, 171–173. The work term is the part of the free energy of activation that brings the reactants together without distorting them along the chemical reaction coordinate.…”

Section: Tunneling In Enzymatic Reactionsmentioning

confidence: 99%

Tunneling in enzymatic and nonenzymatic hydrogen transfer reactions

Truhlar¹

2010

J of Physical Organic Chem

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106

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This paper is a response to an invitation to share my viewpoint by writing an opinion piece (not a review) on proton tunneling, especially from the point of view of whether it has a greater importance in enzymatic reactions than in other reactions. The paper begins with a discussion of the emergence of a conceptual framework for including tunneling in reaction rate calculations; the framework is general enough to include not only transfer of protons but also transfer of hydrogen atoms and hydride ions and their isotopes, and not only enzymatically catalyzed reactions but also nonenzymatic reactions. Then the paper discusses the special issues that arise when the reaction rate under consideration is for an enzyme‐catalyzed reaction. The emphasis is on physical considerations in reaction rate calculations, not on system‐specific comparison of results for different modes of reaction. It is argued that enzymatic and nonenzymatic reactions may be treated within the same basic framework except that ensemble averaging, which is not usually required for gas‐phase reactions, is essential for treating enzyme reactions. Enzymes explicitly discussed include methylamine dehydrogenase, aromatic amine dehydrogenase, E. coli dihydrofolate reductase, hyperthermophilic dihydrofolate reductase, liver alcohol dehydrogenase, methylmalonyl‐CoA mutase, soybean lipoxygenase, copper amine oxidase, pentaerythritol tetranitrate reductase, morphinone reductase, enolase, xylose isomerase, and 4‐oxalocrotonate tautomerase. Copyright © 2010 John Wiley & Sons, Ltd.

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An experimentally based family of potential energy surfaces for hydride transfer between NAD+ analogs

Cited by 100 publications

References 2 publications

Hydrogen Donor–Acceptor Fluctuations from Kinetic Isotope Effects: A Phenomenological Model

Hydrogen Donor–Acceptor Fluctuations from Kinetic Isotope Effects: A Phenomenological Model

Multidimensional Tunneling, Recrossing, and the Transmission Coefficient for Enzymatic Reactions

Tunneling in enzymatic and nonenzymatic hydrogen transfer reactions

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