Differential quantum tunneling contributions in nitroalkane oxidase catalyzed and the uncatalyzed proton transfer reaction

Department of Chemistry, Supercomputing Institute and Digital Technology Center, University of Minnesota, Minneapolis, MN 55455, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 11/2009; 106(49):20734-9. DOI: 10.1073/pnas.0911416106
Source: PubMed

ABSTRACT The proton transfer reaction between the substrate nitroethane and Asp-402 catalyzed by nitroalkane oxidase and the uncatalyzed process in water have been investigated using a path-integral free-energy perturbation method. Although the dominating effect in rate acceleration by the enzyme is the lowering of the quasiclassical free energy barrier, nuclear quantum effects also contribute to catalysis in nitroalkane oxidase. In particular, the overall nuclear quantum effects have greater contributions to lowering the classical barrier in the enzyme, and there is a larger difference in quantum effects between proton and deuteron transfer for the enzymatic reaction than that in water. Both experiment and computation show that primary KIEs are enhanced in the enzyme, and the computed Swain-Schaad exponent for the enzymatic reaction is exacerbated relative to that in the absence of the enzyme. In addition, the computed tunneling transmission coefficient is approximately three times greater for the enzyme reaction than the uncatalyzed reaction, and the origin of the difference may be attributed to a narrowing effect in the effective potentials for tunneling in the enzyme than that in aqueous solution.

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    • "Extensive work by Gao and Truhlar and co-workers [152], and Layfield and Hammes- Schiffer [268] have suggested that it is essential to include NQE to correctly reproduce absolute rates for hydrogen (H • , H + , H − ) transfer reactions. However, NQE contributes only modestly to catalysis [82] [269], although tunneling has been shown to have a small catalytic effect in the case of proton transfer in nitroalkane oxidase [82]. At this point, it is valuable to highlight an important aspect that is often lost in the discussion about the origins of enzyme catalysis and the possible contribution of dynamic effects. "
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