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A comparison of two-electron chemistry performed by the manganese and iron heterodimer and homodimers
Stockholm University, Faculty of Science, Department of Physics.
Stockholm University, Faculty of Science, Department of Physics.
2012 (English)In: Journal of Biological Inorganic Chemistry, ISSN 0949-8257, E-ISSN 1432-1327, Vol. 17, no 3, 363-373 p.Article in journal (Refereed) Published
Abstract [en]

Two-electron chemistry with an iron dimer, a manganese dimer, and a manganese-iron dimer as a catalyst has been modeled using B3LYP* hybrid density functional theory. The recently discovered MnFe proteins form (at least) two functionally distinct groups, performing radical generation (class Ic ribonucleotide reductase subunit II) and substrate oxidations (subunit II-like ligand-binding oxidases, R2lox), respectively. Proteins from the latter group appear to be functionally similar to the diiron carboxylate proteins that perform two-electron oxidations of substrates, such as methane monooxygenase. To qualitatively determine the potential role of a MnFe center in R2lox, methane hydroxylation with the MnFe heterodimer and with the FeFe and MnMn homodimers is studied. The redox potential of the active state of the Mn(IV)Fe(IV) heterodimer is about 7 kcal mol(-1) lower than that of the active state of the Fe(IV)Fe(IV) homodimer, leading to a high barrier for the rate-limiting hydrogen abstraction with the MnFe site. If the entropy loss is not included, the barriers are lower, and the MnFe heterodimer can therefore have a role in R2lox as an oxidase for larger substrates exergonically bound to the protein. A MnMn center has a high barrier both with and without entropy loss. The higher stability of Fe(IV) in the presence of Mn(IV) in the other site compared with a second Fe(IV) suggests an explanation for the presence of the MnFe site in R2lox: to provide a metal center that is capable of two-electron chemistry, and which is more stable and less sensitive to external reductants than an Fe(IV)Fe(IV) site.

Place, publisher, year, edition, pages
2012. Vol. 17, no 3, 363-373 p.
Keyword [en]
Manganese, Iron, Heterodinuclear, Metal specificity, Redox tuning
National Category
Physical Sciences
Research subject
Chemical Physics
Identifiers
URN: urn:nbn:se:su:diva-76255DOI: 10.1007/s00775-011-0858-8ISI: 000301186000004OAI: oai:DiVA.org:su-76255DiVA: diva2:528664
Note
2Available from: 2012-05-28 Created: 2012-05-10 Last updated: 2017-12-07Bibliographically approved
In thesis
1. Manganese and Iron Heterodimers and Homodimers in Enzymes: Insights from Density Functional Theory
Open this publication in new window or tab >>Manganese and Iron Heterodimers and Homodimers in Enzymes: Insights from Density Functional Theory
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The enzyme ribonucleotide reductase (RNR) catalyzes the reduction of ribonucleotides to deoxyribonucleotides, the building blocks of DNA, and is essential for all organisms. Canonical class I RNR R2 proteins use a diiron cofactor to generate a tyrosyl radical, which is required for catalysis. Recent discoveries have established that the different subgroups of class I RNR employ different metal cofactors. Class Ib R2 (R2F) utilizes a dimanganese cofactor and a flavoprotein to generate the tyrosyl radical. Class Ic R2 (R2c) lacks the radical-bearing tyrosine, and instead has an oxidized heterodinuclear manganese-iron center, the first known redox active MnFe cofactor. A second group of MnFe proteins with different functions, denoted R2-like ligand binding oxidases (R2lox), was later identified. R2lox proteins are capable of performing two-electron oxidations and are believed to be hydrocarbon oxidases. In the present thesis density functional theory, a quantum mechanical method, is employed to study the manganese and iron heterodimers and homodimers in the R2 and R2lox proteins, with the aim to shed light on the mechanistic details and stress the main features of the alternative metal centers. Some of the questions addressed are the radical generation with the homodimers and heterodimer in R2, the radical transfer between R2 and the RNR catalytic subunit, and the function of R2lox. A Mn(IV)Fe(III) state is shown to be an equally strong oxidant as a tyrosyl radical, giving a rationalization for the presence of the heterodimer in R2c. A reaction mechanism for the formation of an unprecedented tyrosine-valine crosslink catalyzed by the heterodimer in R2lox is modeled, and the potential of the protein to perform hydroxylations of hydrocarbons based on calculated barriers for methane hydroxylation is discussed. An energetically possible reaction mechanism is suggested for activation of dimanganese R2F by hydrogen peroxide, and a hypothetical role of the flavoprotein in radical generation is proposed.

Place, publisher, year, edition, pages
Stockholm: Department of Physics, Stockholm University, 2012. 86 p.
Keyword
Ribonucleotide reductase, manganese, iron, density functional theory
National Category
Theoretical Chemistry Biochemistry and Molecular Biology Inorganic Chemistry
Research subject
Chemical Physics
Identifiers
urn:nbn:se:su:diva-78814 (URN)978-91-7447-543-2 (ISBN)
Public defence
2012-09-14, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 10:00 (English)
Opponent
Supervisors
Note

At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 4: Submitted. Paper 5: Manuscript.

Available from: 2012-08-23 Created: 2012-08-13 Last updated: 2015-10-27Bibliographically approved

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