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Reductive cleavage of the O-O bond in multicopper oxidases: a QM/MM and QM study

Srnec, Martin; Ryde, Ulf LU and Rulisek, Lubomir (2011) In Faraday Discussions 148. p.41-53
Abstract
The key step in the reaction mechanism of multicopper oxidases (MCOs)-the cleavage of the O-O bond in O-2-has been investigated using combined quantum mechanical and molecular mechanical (QM/MM) methods. This process represents a reaction pathway from the peroxy intermediate after it accepts one electron from the nearby type-1 Cu site to the experimentally-observed native intermediate, which is the only fully oxidised catalytically relevant state in MCOs. Scans of the QM(DFT)/MM potential energy surface have allowed us to obtain estimates of the activation energies. Furthermore, vacuum calculations on a smaller model of the active site have allowed us to estimate the entropy contributions to the barrier height and to obtain further insight... (More)
The key step in the reaction mechanism of multicopper oxidases (MCOs)-the cleavage of the O-O bond in O-2-has been investigated using combined quantum mechanical and molecular mechanical (QM/MM) methods. This process represents a reaction pathway from the peroxy intermediate after it accepts one electron from the nearby type-1 Cu site to the experimentally-observed native intermediate, which is the only fully oxidised catalytically relevant state in MCOs. Scans of the QM(DFT)/MM potential energy surface have allowed us to obtain estimates of the activation energies. Furthermore, vacuum calculations on a smaller model of the active site have allowed us to estimate the entropy contributions to the barrier height and to obtain further insight into the reaction by comparing the small cluster model with the QM/MM model, which includes the entire protein. Owing to the complicated electronic structure of these low-spin exchange coupled systems, multireference quantum chemical calculations at the complete-active space second-order perturbation theory (CASPT2) were used in an attempt to benchmark the barrier heights obtained at the DFT(B3LYP) level. Our best estimate of the activation barrier is Delta G = 60-65 kJ mol(-1), in good agreement with the experimental barrier of similar to 55 kJ mol(-1), which can be inferred from the experimental rate constant of k > 350 s(-1). It has also been shown that the reaction involves protonation of the O-2 moiety before bond cleavage. The proton likely comes from a nearby carboxylate residue which was recently suggested by the experiments. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Faraday Discussions
volume
148
pages
41 - 53
publisher
Royal Society of Chemistry
external identifiers
  • wos:000285361500003
  • scopus:79952261204
ISSN
1364-5498
DOI
10.1039/c004476h
language
English
LU publication?
yes
id
cf0cd0de-7c7c-4d6a-aedc-ffae9bb6d59f (old id 1773882)
date added to LUP
2011-02-01 10:42:45
date last changed
2017-08-13 03:26:15
@article{cf0cd0de-7c7c-4d6a-aedc-ffae9bb6d59f,
  abstract     = {The key step in the reaction mechanism of multicopper oxidases (MCOs)-the cleavage of the O-O bond in O-2-has been investigated using combined quantum mechanical and molecular mechanical (QM/MM) methods. This process represents a reaction pathway from the peroxy intermediate after it accepts one electron from the nearby type-1 Cu site to the experimentally-observed native intermediate, which is the only fully oxidised catalytically relevant state in MCOs. Scans of the QM(DFT)/MM potential energy surface have allowed us to obtain estimates of the activation energies. Furthermore, vacuum calculations on a smaller model of the active site have allowed us to estimate the entropy contributions to the barrier height and to obtain further insight into the reaction by comparing the small cluster model with the QM/MM model, which includes the entire protein. Owing to the complicated electronic structure of these low-spin exchange coupled systems, multireference quantum chemical calculations at the complete-active space second-order perturbation theory (CASPT2) were used in an attempt to benchmark the barrier heights obtained at the DFT(B3LYP) level. Our best estimate of the activation barrier is Delta G = 60-65 kJ mol(-1), in good agreement with the experimental barrier of similar to 55 kJ mol(-1), which can be inferred from the experimental rate constant of k > 350 s(-1). It has also been shown that the reaction involves protonation of the O-2 moiety before bond cleavage. The proton likely comes from a nearby carboxylate residue which was recently suggested by the experiments.},
  author       = {Srnec, Martin and Ryde, Ulf and Rulisek, Lubomir},
  issn         = {1364-5498},
  language     = {eng},
  pages        = {41--53},
  publisher    = {Royal Society of Chemistry},
  series       = {Faraday Discussions},
  title        = {Reductive cleavage of the O-O bond in multicopper oxidases: a QM/MM and QM study},
  url          = {http://dx.doi.org/10.1039/c004476h},
  volume       = {148},
  year         = {2011},
}