Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Formation of the Unusual Tyrosine-Valine Crosslink in the Manganese-Iron Heterodimer Oxidase from Mycobacterium tuberculosis
Stockholm University, Faculty of Science, Department of Physics.
Stockholm University, Faculty of Science, Department of Physics.
Stockholm University, Faculty of Science, Department of Physics.
(English)Manuscript (preprint) (Other academic)
Keyword [en]
Manganese-iron, post-translational crosslink, tyrosine, valine, density functional theory
National Category
Theoretical Chemistry Inorganic Chemistry Biochemistry and Molecular Biology
Research subject
Chemical Physics
Identifiers
URN: urn:nbn:se:su:diva-78813OAI: oai:DiVA.org:su-78813DiVA: diva2:544165
Available from: 2012-08-13 Created: 2012-08-13 Last updated: 2012-08-14Bibliographically 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

Open Access in DiVA

No full text

Search in DiVA

By author/editor
Roos, KatarinaBlomberg, Margareta R. A.Siegbahn, Per E. M.
By organisation
Department of Physics
Theoretical ChemistryInorganic ChemistryBiochemistry and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar

urn-nbn

Altmetric score

urn-nbn
Total: 47 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf