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A combined quantum and molecular mechanical study of the O-2 reductive cleavage in the catalytic cycle of multicopper oxidases

Rulisek, Lubomir LU ; Solomon, E I and Ryde, Ulf LU (2005) In Inorganic Chemistry 44(16). p.5612-5628
Abstract
The four-electron reduction of dioxygen to water in multicopper oxidases takes place in a trinuclear copper cluster, which is linked to a mononuclear blue copper site, where the substrates are oxidized. Recently, several intermediates in the catalytic cycle have been spectroscopically characterized, and two possible structural models have been suggested for both the peroxy and native intermediates, In this study, these spectroscopic results are complemented by hybrid quantum and molecular mechanical (QM/MM) calculations, taking advantage of recently available crystal structures with a full complement of copper ions. Thereby, we obtain optimized molecular structures for all of the Experimentally studied intermediates involved in the... (More)
The four-electron reduction of dioxygen to water in multicopper oxidases takes place in a trinuclear copper cluster, which is linked to a mononuclear blue copper site, where the substrates are oxidized. Recently, several intermediates in the catalytic cycle have been spectroscopically characterized, and two possible structural models have been suggested for both the peroxy and native intermediates, In this study, these spectroscopic results are complemented by hybrid quantum and molecular mechanical (QM/MM) calculations, taking advantage of recently available crystal structures with a full complement of copper ions. Thereby, we obtain optimized molecular structures for all of the Experimentally studied intermediates involved in the reductive cleavage of the O-2 molecule and energy profiles for individual reaction steps, This allows identification of the experimentally observed intermediates and further insight into the reaction mechanism that is probably relevant for the whole class of multicopper oxidases, We suggest that the peroxy intermediate contains an O-2(2-) ion, in which one oxygen atom bridges the type 2 copper ion and one of the type 3 copper ions, whereas the other one coordinates to the other type 3 copper ion, One-electron reduction of this intermediate triggers the cleavage of the O-O bond, which involves the uptake of a proton, The product of this cleavage is the observed native intermediate, which we suggest to contain a O-2 ion coordinated to all three of the copper ions in the center of the cluster. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Inorganic Chemistry
volume
44
issue
16
pages
5612 - 5628
publisher
The American Chemical Society
external identifiers
  • wos:000231030900012
  • pmid:16060610
  • scopus:23844550273
ISSN
1520-510X
DOI
10.1021/ic050092z
language
English
LU publication?
yes
id
5819617a-b12f-474b-bbcd-976c76e2a5d5 (old id 152715)
date added to LUP
2007-07-17 13:42:41
date last changed
2017-10-08 03:28:56
@article{5819617a-b12f-474b-bbcd-976c76e2a5d5,
  abstract     = {The four-electron reduction of dioxygen to water in multicopper oxidases takes place in a trinuclear copper cluster, which is linked to a mononuclear blue copper site, where the substrates are oxidized. Recently, several intermediates in the catalytic cycle have been spectroscopically characterized, and two possible structural models have been suggested for both the peroxy and native intermediates, In this study, these spectroscopic results are complemented by hybrid quantum and molecular mechanical (QM/MM) calculations, taking advantage of recently available crystal structures with a full complement of copper ions. Thereby, we obtain optimized molecular structures for all of the Experimentally studied intermediates involved in the reductive cleavage of the O-2 molecule and energy profiles for individual reaction steps, This allows identification of the experimentally observed intermediates and further insight into the reaction mechanism that is probably relevant for the whole class of multicopper oxidases, We suggest that the peroxy intermediate contains an O-2(2-) ion, in which one oxygen atom bridges the type 2 copper ion and one of the type 3 copper ions, whereas the other one coordinates to the other type 3 copper ion, One-electron reduction of this intermediate triggers the cleavage of the O-O bond, which involves the uptake of a proton, The product of this cleavage is the observed native intermediate, which we suggest to contain a O-2 ion coordinated to all three of the copper ions in the center of the cluster.},
  author       = {Rulisek, Lubomir and Solomon, E I and Ryde, Ulf},
  issn         = {1520-510X},
  language     = {eng},
  number       = {16},
  pages        = {5612--5628},
  publisher    = {The American Chemical Society},
  series       = {Inorganic Chemistry},
  title        = {A combined quantum and molecular mechanical study of the O-2 reductive cleavage in the catalytic cycle of multicopper oxidases},
  url          = {http://dx.doi.org/10.1021/ic050092z},
  volume       = {44},
  year         = {2005},
}