Tunneling in enzymatic and nonenzymatic hydrogen transfer reactions

Abstract

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.

Wide-dynamic-range kinetic investigations of deep proton tunnelling in proteins

“…Other approaches 12,27,36 factor out and quantize the D-A vibration (~100 fs), as well as the much higher frequency (~10 fs) vibrational mode of the tunneling particle, which is a common feature in all analytical models (see Supplementary Discussion 4). Computationally based transition state theories have also been applied in the large curvature limit to account for deep tunneling 22 .…”

“…Within the class of "factorized" analytical models 12,22,27,36 In the following, we assume that a single deep proton tunneling reaction is the ratelimiting event for the overall transport process in GFP (i.e., the other two protons follow in asynchronous but concerted fashion). This assumption is based on the longer tunnel distances and larger reorganization energy that must be invoked for simultaneous (synchronous) multiple proton tunneling.…”

“…The proton wire in GFP includes amino acid components that are found in other biological systems 17 and, importantly, this wire has evolved to include a high pK a residue (Ser205) as an active transport element. Thus, the detailed experiments presented here provide insight on the structure and function of such wires as well as an opportunity to test various theoretical models that apply to PT in proteins 8,10,12,[22][23][24][25][26][27] .…”

“…The deep tunneling channel, or "large curvature tunneling" 10,22 , dominates the rate when the barrier along the OH coordinate is much larger than the zero-point energy of the OH oscillator. Under these conditions, the proton vibrational levels of the reactant and product states are only weakly mixed and their energy splitting (Δ ) is much smaller than .…”

“…1, we analyze the kinetic data using a simplified (but analytic) deep tunneling model 27 that factors out the key vibrational motions of the tunneling particle and the donor and acceptor oxygen atoms, while treating the rest of the surroundings using a generalized environmental coordinate. Because there is no electronic state change during the reaction, it is considered to be electronically adiabatic 12,22 . This allows the rate to be calculated on an absolute scale, without having to estimate the unknown electronic matrix element that appears in the electronically non-adiabatic limit (e.g., when longer range electron transport is also involved).…”