Advanced

Theoretical Studies of the Active-Site Structure, Spectroscopic and Thermodynamic Properties, and Reaction Mechanism of Multicopper Oxidases

Rulisek, Lubomir LU and Ryde, Ulf LU (2013) In Coordination Chemistry Reviews 257. p.445-458
Abstract
In this article, we review recent theoretical work that has complemented the extensive experimental data available for multicopper oxidases (MCO) and led to the elucidation of the reaction mechanism of this class of enzymes. The MCOs couple four one-electron oxidations of substrates at the mononuclear type 1 copper (Cu-T1) site with the four-electron reduction of dioxygen at the trinuclear copper cluster (TNC). The TNC consists of three copper ions arranged in a unique triangular fashion. In its oxidised form and in some experimentally observed intermediates (the peroxy and native intermediates), this leads to a magnetic coupling of the unpaired electrons of the three copper ions, resulting in unusual spectroscopic features. By correlating... (More)
In this article, we review recent theoretical work that has complemented the extensive experimental data available for multicopper oxidases (MCO) and led to the elucidation of the reaction mechanism of this class of enzymes. The MCOs couple four one-electron oxidations of substrates at the mononuclear type 1 copper (Cu-T1) site with the four-electron reduction of dioxygen at the trinuclear copper cluster (TNC). The TNC consists of three copper ions arranged in a unique triangular fashion. In its oxidised form and in some experimentally observed intermediates (the peroxy and native intermediates), this leads to a magnetic coupling of the unpaired electrons of the three copper ions, resulting in unusual spectroscopic features. By correlating experimental and theoretical data, an unambiguous mapping between the structural, energetic and spectroscopic properties of the various intermediates in the MCO reaction cycle can be established. In terms of theory, these studies involved quantum mechanics (QM; density-functional theory and multi-reference self-consistent field) calculations, combined QM and molecular mechanics (QM/MM) modelling, ranging from standard QM/MM optimisations to the combination of QM/MM optimisation with EXAFS spectroscopy and QM/MM free-energy perturbations to accurately address phenomena such as the Cu-T1 → TNC electron transfer, as well as the reduction potentials and acid constants of all the putative intermediates in the MCO reaction cycle. In summary, we try to demonstrate in this review that the MCOs are not only an attractive playground for theoretical methods, but the results of the calculations (when carefully correlated with and benchmarked against experimental data) can also be used to draw unambiguous conclusions about MCO structure and reactivity. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Multi-copper oxidases, Laccase, quantum mechanics, QM/MM, EXAFS, CASPT2
in
Coordination Chemistry Reviews
volume
257
pages
445 - 458
publisher
Elsevier
external identifiers
  • wos:000312762200011
  • scopus:84870390826
ISSN
0010-8545
DOI
10.1016/j.ccr.2012.04.019
language
English
LU publication?
yes
id
35edb799-7f06-4bd3-a425-483757721d40 (old id 3412401)
date added to LUP
2013-01-30 06:45:47
date last changed
2019-02-20 05:09:58
@article{35edb799-7f06-4bd3-a425-483757721d40,
  abstract     = {In this article, we review recent theoretical work that has complemented the extensive experimental data available for multicopper oxidases (MCO) and led to the elucidation of the reaction mechanism of this class of enzymes. The MCOs couple four one-electron oxidations of substrates at the mononuclear type 1 copper (Cu-T1) site with the four-electron reduction of dioxygen at the trinuclear copper cluster (TNC). The TNC consists of three copper ions arranged in a unique triangular fashion. In its oxidised form and in some experimentally observed intermediates (the peroxy and native intermediates), this leads to a magnetic coupling of the unpaired electrons of the three copper ions, resulting in unusual spectroscopic features. By correlating experimental and theoretical data, an unambiguous mapping between the structural, energetic and spectroscopic properties of the various intermediates in the MCO reaction cycle can be established. In terms of theory, these studies involved quantum mechanics (QM; density-functional theory and multi-reference self-consistent field) calculations, combined QM and molecular mechanics (QM/MM) modelling, ranging from standard QM/MM optimisations to the combination of QM/MM optimisation with EXAFS spectroscopy and QM/MM free-energy perturbations to accurately address phenomena such as the Cu-T1 → TNC electron transfer, as well as the reduction potentials and acid constants of all the putative intermediates in the MCO reaction cycle. In summary, we try to demonstrate in this review that the MCOs are not only an attractive playground for theoretical methods, but the results of the calculations (when carefully correlated with and benchmarked against experimental data) can also be used to draw unambiguous conclusions about MCO structure and reactivity.},
  author       = {Rulisek, Lubomir and Ryde, Ulf},
  issn         = {0010-8545},
  keyword      = {Multi-copper oxidases,Laccase,quantum mechanics,QM/MM,EXAFS,CASPT2},
  language     = {eng},
  pages        = {445--458},
  publisher    = {Elsevier},
  series       = {Coordination Chemistry Reviews},
  title        = {Theoretical Studies of the Active-Site Structure, Spectroscopic and Thermodynamic Properties, and Reaction Mechanism of Multicopper Oxidases},
  url          = {http://dx.doi.org/10.1016/j.ccr.2012.04.019},
  volume       = {257},
  year         = {2013},
}