Investigation of the Hydroxylation Mechanism of Noncoupled Copper Oxygenases by Ab Initio Molecular Dynamics Simulations
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Otros documentos de la autoría: Meliá, Conchín; Ferrer, Silvia; Rezác, Jan; Parisel, Olivier; Reinaud, Olivia; Moliner, Vicent; de la LANDE, Aurélien
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http://dx.doi.org/10.1002/chem.201301000 |
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Título
Investigation of the Hydroxylation Mechanism of Noncoupled Copper Oxygenases by Ab Initio Molecular Dynamics SimulationsAutoría
Fecha de publicación
2013-11-20Editor
WileyISSN
0947-6539; 1521-3765Cita bibliográfica
MELIÁ, Conchín, et al. Investigation of the Hydroxylation Mechanism of Noncoupled Copper Oxygenases by Ab Initio Molecular Dynamics Simulations. Chemistry-A European Journal, 2013, vol. 19, no 51, p. 17328-17337Tipo de documento
info:eu-repo/semantics/articleVersión de la editorial
http://onlinelibrary.wiley.com/doi/10.1002/chem.201301000/abstractVersión
info:eu-repo/semantics/publishedVersionPalabras clave / Materias
Resumen
In Nature, the family of copper monooxygenases comprised of peptidylglycine α-hydroxylating monooxygenase (PHM), dopamine β-monooxygenase (DβM), and tyramine β-monooxygenase (TβM) is known to perform dioxygen-dependent ... [+]
In Nature, the family of copper monooxygenases comprised of peptidylglycine α-hydroxylating monooxygenase (PHM), dopamine β-monooxygenase (DβM), and tyramine β-monooxygenase (TβM) is known to perform dioxygen-dependent hydroxylation of aliphatic C[BOND]H bonds by using two uncoupled metal sites. In spite of many investigations, including biochemical, chemical, and computational, details of the C[BOND]H bond oxygenation mechanism remain elusive. Herein we report an investigation of the mechanism of hydroxylation by PHM by using hybrid quantum/classical potentials (i.e., QM/MM). Although previous investigations using hybrid QM/MM techniques were restricted to geometry optimizations, we have carried out ab initio molecular dynamics simulations in order to include the intrinsic flexibility of the active sites in the modeling protocol. The major finding of this study is an extremely fast rebound step after the initial hydrogen-abstraction step promoted by the cupric–superoxide adduct. The hydrogen-abstraction/rebound sequence leads to the formation of an alkyl hydroperoxide intermediate. Long-range electron transfer from the remote copper site subsequently triggers its reduction to the hydroxylated substrate. We finally show two reactivity consequences inherent in the new mechanistic proposal, the investigation of which would provide a means to check its validity by experimental means. [-]
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Chemistry-A European Journal, 2013, vol. 19, no 51Derechos de acceso
Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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