Using Grote-Hynes Theory To Quantify Dynamical Effects on the Reaction Rate of Enzymatic Processes. The Case of Methyltransferases

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• 作者：Raquel Castillo ; Maite Roca ; Alejandro Soriano ; Vicente Moliner ; Iñ ; aki Tuñ ; &oacute ; n
• 刊名：Journal of Physical Chemistry B
• 出版年：2008
• 出版时间：January 17, 2008
• 年：2008
• 卷：112
• 期：2
• 页码：529 - 534
• 全文大小：129K
• 年卷期：v.112,no.2(January 17, 2008)
• ISSN：1520-5207

文摘

Dynamical effects have recently received much attention in the context of the theoretical investigation ofenzymatic catalysis. In this paper we use a combination of Grote-Hynes theory with quantum mechanical/molecular mechanical modeling that is a powerful tool to understand and quantify these dynamical effects ina particular enzyme, the glycine N-methyltransferase (GNMT). Comparison of the results obtained for thisenzyme with another methyltransferase (catechol O-methyltransferase, COMT) allows us to understand thedifferent nature of the coupling of the environment to the reaction coordinate as a function of the electrostaticinteraction established by the reactive subsystem. The transmission coefficients obtained using Grote-Hynestheory are in excellent agreement with molecular dynamics estimations and show that the coupling is higherin GNMT than in COMT. The larger friction observed in GNMT is explained on the basis of the interactionestablished by the substrate in the active site. The larger value of the friction leads to a smaller value of thereaction frequency and thus also to a larger disagreement with the estimation of the transmission coefficientbased on the frozen environment approach.