Solute Solvent Dynamics and Energetics in Enzyme Catalysis: The SN2 Reaction of Dehalogenase as a General Benchmark
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- 作者：Mats H. M. Olsson and Arieh Warshel
- 刊名：Journal of the American Chemical Society
- 出版年：2004
- 出版时间：November 24, 2004
- 年：2004
- 卷：126
- 期：46
- 页码：15167 - 15179
- 全文大小：376K
- 年卷期：v.126,no.46(November 24, 2004)
- ISSN：1520-5126
文摘
One of the most useful ways of describing and analyzing enzyme catalysis is the description ofthe enzyme as an effective solvent for the reacting substrate. Here, we illustrate this concept by consideringthe SN2 reaction of haloalkan dehalogenase (DhlA), analyze the energetics and dynamics of the solventcoordinate, and evaluate their relative catalytic effect. It is demonstrated that almost the entire catalyticeffect is associated with the preorganization of the protein-solvent coordinate. It is clarified that this effectis associated with the fact that the transition state is "solvated" by the protein more than in the referencesolution reaction. This effect is fundamentally different than the frequently proposed desolvation mechanism.The possible catalytic role of dynamical effects is analyzed by considering several reasonable ways ofdefining "dynamical contributions to catalysis". It is found that these contributions are small regardless ofthe definition used. It is also shown that the effect of the difference in the relaxation time of the solventcoordinate in the enzyme and solution reaction is rather trivial relative to the effect of the correspondingchanges in reorganization free energy.