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

Li, Jilai LU ; Farrokhnia, Maryam LU ; Rulisek, Lubomir and Ryde, Ulf LU (2015) In The Journal of Physical Chemistry Part B 119(26). p.8268-8284
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
The Journal of Physical Chemistry Part B
volume
119
issue
26
pages
8268 - 8284
publisher
The American Chemical Society
external identifiers
  • pmid:26039490
  • wos:000357623400005
  • scopus:84947465829
ISSN
1520-5207
DOI
10.1021/acs.jpcb.5b02864
language
English
LU publication?
yes
id
752a1693-99d8-4dce-b26b-4459dfe37856 (old id 7508396)
date added to LUP
2015-07-10 11:25:10
date last changed
2017-10-08 03:19:34
@article{752a1693-99d8-4dce-b26b-4459dfe37856,
  abstract     = {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.},
  author       = {Li, Jilai and Farrokhnia, Maryam and Rulisek, Lubomir and Ryde, Ulf},
  issn         = {1520-5207},
  language     = {eng},
  number       = {26},
  pages        = {8268--8284},
  publisher    = {The American Chemical Society},
  series       = {The Journal of Physical Chemistry Part B},
  title        = {Catalytic Cycle of Multicopper Oxidases Studied by Combined Quantum- and Molecular-Mechanical Free-Energy Perturbation Methods.},
  url          = {http://dx.doi.org/10.1021/acs.jpcb.5b02864},
  volume       = {119},
  year         = {2015},
}