Catalytic Cycle of Multicopper Oxidases Studied by Combined Quantum- and Molecular-Mechanical Free-Energy Perturbation Methods

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• 作者：Jilai Li ; Maryam Farrokhnia ; Lubom铆r Rul铆拧ek ; Ulf Ryde
• 刊名：Journal of Physical Chemistry B
• 出版年：2015
• 出版时间：July 2, 2015
• 年：2015
• 卷：119
• 期：26
• 页码：8268-8284
• 全文大小：460K
• ISSN：1520-5207

文摘

We have used combined quantum mechanical and molecular mechanical free-energy perturbation methods in combination with explicit solvent simulations to study the reaction mechanism of the multicopper oxidases, in particular, the regeneration of the reduced state from the native intermediate. For 52 putative states of the trinuclear copper cluster, differing in the oxidation states of the copper ions and the protonation states of water- and O₂-derived ligands, we have studied redox potentials, acidity constants, isomerization reactions, as well as water- and O₂ binding reactions. Thereby, we can propose a full reaction mechanism of the multicopper oxidases with atomic detail. We also show that the two copper sites in the protein communicate so that redox potentials and acidity constants of one site are affected by up to 0.2 V or 3 pK_a units by a change in the oxidation state of the other site.