Internal Enzyme Motions as a Source of Catalytic Activity:  Rate-Promoting Vibrations and Hydrogen Tunneling

Antoniou, Dimitri; Schwartz, Steven D.

doi:10.1021/jp004547b

Cited by 144 publications

(176 citation statements)

References 34 publications

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“…To a first approximation, the n p can be thought of as arising from the confinement of the proton in the potential well provided by water oxygens in the protein hydration shell, with a oxygen-oxygen first neighbor distance smaller that the corresponding distance in the bulk phase. This could support the presence of tunneling effects even at room temperature [31], playing an important role in the biological function [32,33].…”

mentioning

confidence: 55%

Proton Momentum Distribution in a Protein Hydration Shell

et al. 2007

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The momentum distribution of protons in the hydration shell of a globular protein has been measured through deep inelastic neutron scattering at 180 and 290 K, below and above the crossover temperature T c 1:23T g , where T g 219 K is the glass transition temperature. It is found that the mean kinetic energy of the water hydrogens shows no temperature dependence, but the measurements are accurate enough to indicate a sensible change of momentum distribution and effective potential felt by protons, compatible with the transition from a single to a double potential well. This could support the presence of tunneling effects even at room temperature, playing an important role in biological function.

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confidence: 55%

Proton Momentum Distribution in a Protein Hydration Shell

et al. 2007

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“…489 ) Various explanations are possible for the average energy of molecules that react increasing less rapidly than the average energy of all possible reactants; for example, there could be a pool of especially reactive states that does not broaden as temperature increases. Antoniou and Schwartz 119 have postulated that convex Arrhenius plots could arise from tunneling strongly coupled to a promoting vibration. It is not clear if this stimulating suggestion is the correct explanation in this case, but it raises the issue that it is dangerous to interpret the temperature dependence of Arrhenius plots of ratios of rate constants when one does not understand the temperature dependences of the individual rate constants.…”

Section: Thermophilic Alcohol Dehydrogenasementioning

confidence: 99%

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

2006

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“…But we and others have suggested that vibrational motions within the protein may in fact be coupled to the reaction coordinate (4). Previous work in our group has suggested the coupling of these vibrational motions to the reaction coordinate and has developed methods to study their effect on enzyme reactions (5).…”

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confidence: 98%

Reaction coordinate of an enzymatic reaction revealed by transition path sampling

Quaytman¹,

Schwartz

2007

Proc. Natl. Acad. Sci. U.S.A.

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The transition path sampling method previously applied in our group to the reaction catalyzed by lactate dehydrogenase was used to generate a transition path ensemble for this reaction. Based on analysis of the reactive trajectories generated, important residues behind the active site were implicated in a compressional motion that brought the donor-acceptor atoms of the hydride closer together. In addition, residues behind the active site were implicated in a relaxational motion, locking the substrate in product formation. Although this suggested that the compressionrelaxation motions of these residues were important to catalysis, it remained unproven. In this work, we used committor distribution analysis to show that these motions are integral components of the reaction coordinate.protein dynamics ͉ catalysis T he relationship between enzymatic structure and function remains an area of intense research. Many studies have demonstrated that factors such as electrostatic and entropic effects are significant to enzyme function (1). The role of dynamics in catalysis, however, is less well understood. Protein motions such as conformational fluctuations on the millisecond timescale have been shown to influence substrate binding and the height of the barrier to reaction. The role of vibrational motions on the femtosecond to picosecond timescale and their connection to catalysis remain controversial. It has been suggested that the vibrational motions that exist within the protein are in equilibrium with the reaction and thermally averaged along the reaction coordinate (2, 3). But we and others have suggested that vibrational motions within the protein may in fact be coupled to the reaction coordinate (4). Previous work in our group has suggested the coupling of these vibrational motions to the reaction coordinate and has developed methods to study their effect on enzyme reactions (5).The search for these subpicosecond motions (''protein promoting vibrations'') was first applied to the enzyme horse liver alcohol dehydrogenase. This work suggested there existed motions, protein-promoting vibrations (PPVs), that coupled directly to the reaction coordinate and that were on the timescale of barrier crossing (6). The algorithm was then tested on another enzyme system lactate dehydrogenase (LDH), and similar PPVs were identified that, along with conformational fluctuations, helped explain the preference of the heart isoform to produce pyruvate and of muscle isoform to produce lactate (7).Further investigation into the mechanism of LDH was achieved with the transition path sampling (TPS) method (8). TPS is a computational method that can simulate rare events in complex systems. Using a Monte Carlo approach, a reactive path ensemble connecting reactants to products can be defined without prior knowledge of the reaction coordinate. This method allows mechanistic details to be identified from reactive paths generated with no bias (9). A reactive path ensemble was generated for LDH, and it was found that, in all reactive trajectori...

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Internal Enzyme Motions as a Source of Catalytic Activity: Rate-Promoting Vibrations and Hydrogen Tunneling

Cited by 144 publications

References 34 publications

Proton Momentum Distribution in a Protein Hydration Shell

Proton Momentum Distribution in a Protein Hydration Shell

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

Reaction coordinate of an enzymatic reaction revealed by transition path sampling

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