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A Theoretical Study of the Cis-Dihydroxylation Mechanism in Naphthalene 1,2-dioxygenase
Stockholm University, Faculty of Science, Department of Physics.
Stockholm University, Faculty of Science, Department of Physics.
Stockholm University, Faculty of Science, Department of Physics.
2004 (English)In: Journal of Biological Inorganic Chemistry, ISSN 0949-8257, E-ISSN 1432-1327, Vol. 9, no 4, 439-452 p.Article in journal (Refereed) Published
Abstract [en]

The catalytic mechanism of naphthalene 1,2-dioxygenase has been investigated by means of hybrid density functional theory. This Rieske-type enzyme, which contains an active site hosting a mononuclear non-heme iron(II) complex, uses dioxygen and two electrons provided by NADH to carry out the cis-dihydroxylation of naphthalene. Since a (hydro)peroxo-iron(III) moiety has been proposed to be involved in the catalytic cycle, it was probed whether and how this species is capable of cis-dihydroxylation of the aromatic substrate. Different oxidation and protonation states of the Fe–O2 complex were studied on the basis of the crystal structure of the enzyme with oxygen bound side-on to iron. It was found that feasible reaction pathways require a protonated peroxo ligand, FeIII–OOH; the deprotonated species, the peroxo-iron(III) complex, was found to be inert toward naphthalene. Among the different chemical patterns which have been explored, the most accessible one involves an epoxide intermediate, which may subsequently evolve toward an arene cation, and finally to the cis-diol. The possibility that an iron(V)-oxo species is formed prior to substrate hydroxylation was also examined, but found to implicate a rather high energy barrier. In contrast, a reasonably low barrier might lead to a high-valent iron-oxo species [i.e. iron(IV)-oxo] if a second external electron is supplied to the mononuclear iron center before dioxygenation.

Place, publisher, year, edition, pages
2004. Vol. 9, no 4, 439-452 p.
Keyword [en]
Density functional calculations, Enzyme catalysis, Non-heme iron enzymes, O–O bond activation
URN: urn:nbn:se:su:diva-22674DOI: 10.1007/s00775-004-0537-0OAI: diva2:189250
Part of urn:nbn:se:su:diva-103Available from: 2004-04-15 Created: 2004-04-15 Last updated: 2010-07-27Bibliographically approved
In thesis
1. Theoretical studies of mononuclear non-heme iron active sites
Open this publication in new window or tab >>Theoretical studies of mononuclear non-heme iron active sites
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The quantum chemical investigations presented in this thesis use hybrid density functional theory to shed light on the catalytic mechanisms of mononuclear non-heme iron oxygenases, accommodating a ferrous ion in their active sites. More specifically, the dioxygen activation process and the subsequent oxidative reactions in the following enzymes were studied: tetrahydrobiopterin-dependent hydroxylases, naphthalene 1,2-dioxygenase and α-ketoglutarate-dependent enzymes. In light of many experimental efforts devoted to the functional mimics of non-heme iron oxygenases, the reactivity of functional analogues was also examined.

The computed energetics and the available experimental data served to assess the feasibility of the reaction mechanisms investigated. Dioxygen activation in tetrahydrobiopterin- and α-ketoglutarate-dependent enzymes were found to involve a high-valent iron-oxo species, which was then capable of substrate hydroxylation. In the case of naphthalene 1,2-dioxygenase, the reactivity of an iron(III)-hydroxperoxo species toward the substrate was investigated and compared to the biomimetic counterpart.

Place, publisher, year, edition, pages
Stockholm: Fysikum, 2004. 86 p.
quantum chemistry, enzyme catalysis, iron enzymes
National Category
Theoretical Chemistry
urn:nbn:se:su:diva-103 (URN)91-7265-857-6 (ISBN)
Public defence
2004-05-07, sal FA32, AlbaNova universitetscentrum, Roslagstullsbacken 21, Stockholm, 10:00
Available from: 2004-04-15 Created: 2004-04-15Bibliographically approved

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Blomberg, Margareta R. A.Siegbahn, Per E. M.
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