A Comparative Study of Claisen and Cope Rearrangements Catalyzed by Chorismate Mutase. An Insight into Enzymatic Efficiency: Transition State Stabilization or Substrate Preorganization?
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- 作者：Sergio Martí ; Juan André ; s ; Vicente Moliner ; Estanislao Silla ; Iñ ; aki Tuñ ; ó ; n ; and Juan Bertrá ; n
- 刊名：Journal of the American Chemical Society
- 出版年：2004
- 出版时间：January 14, 2004
- 年：2004
- 卷：126
- 期：1
- 页码：311 - 319
- 全文大小：199K
- 年卷期：v.126,no.1(January 14, 2004)
- ISSN：1520-5126
文摘
In this work we present a detailed analysis of the activation free energies and averaged interactionsfor the Claisen and Cope rearrangements of chorismate and carbachorismate catalyzed by Bacillus subtilischorismate mutase (BsCM) using quantum mechanics/molecular mechanics (QM/MM) simulation methods.In gas phase, both reactions are described as concerted processes, with the activation free energy forcarbachorismate being about 10-15 kcal mol-1 larger than for chorismate, at the AM1 and B3LYP/6-31G*levels. Aqueous solution and BsCM active site environments reduce the free energy barriers for bothreactions, due to the fact that in these media the two carboxylate groups can be approached more easilythan in the gas phase. The enzyme specifically reduces the activation free energy of the Claisenrearrangement about 3 kcal mol-1 more than that for the Cope reaction. This result is due to a largertransition state stabilization associated to the formation of a hydrogen bond between Arg90 and the etheroxygen. When this oxygen atom is changed by a methylene group, the interaction is lost and Arg90 movesinside the active site establishing stronger interactions with one of the carboxylate groups. This fact yieldsa more intense rearrangement of the substrate structure. Comparing two reactions in the same enzyme,we have been able to obtain conclusions about the relative magnitude of the substrate preorganizationand transition state stabilization effects. Transition state stabilization seems to be the dominant effect inthis case.