Catalytic Cycle of Multicopper Oxidases Studied by Combined Quantum- and Molecular-Mechanical Free-Energy Perturbation Methods
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Models, Chemical * MeSH
- Isomerism MeSH
- Catalysis MeSH
- Copper chemistry MeSH
- Oxidation-Reduction MeSH
- Oxidoreductases chemistry metabolism MeSH
- Protons MeSH
- Solvents MeSH
- Molecular Dynamics Simulation MeSH
- Electron Transport MeSH
- Water chemistry MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- copper oxidase MeSH Browser
- Copper MeSH
- Oxidoreductases MeSH
- Protons MeSH
- Solvents MeSH
- Water MeSH
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 pKa units by a change in the oxidation state of the other site.
References provided by Crossref.org
Mono- and binuclear non-heme iron chemistry from a theoretical perspective
