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

0446363 - ÚOCHB 2016 RIV US eng J - Journal Article
Li, J. - Farrokhnia, M. - Rulíšek, Lubomír - Ryde, U.
Catalytic Cycle of Multicopper Oxidases Studied by Combined Quantum- and Molecular-Mechanical Free-Energy Perturbation Methods.
Journal of Physical Chemistry B. Roč. 119, č. 26 (2015), s. 8268-8284. ISSN 1520-6106. E-ISSN 1520-5207
R&D Projects: GA ČR(CZ) GA14-31419S
Institutional support: RVO:61388963
Keywords : multi-copper oxidases * QM/MM calculations * reduction potentials * pKa acidity constants
Subject RIV: CF - Physical ; Theoretical Chemistry
Impact factor: 3.187, year: 2015

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 O-2-derived ligands, we have studied redox potentials, acidity constants, isomerization reactions, as well 48 water- and O-2 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.
Permanent Link: http://hdl.handle.net/11104/0248367