uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Semiquinone-Induced Maturation of Bacillus anthracis Ribonucleotide Reductase by a Superoxide Intermediate
2014 (English)In: Journal of Biological ChemistryArticle in journal (Refereed) Published
Abstract [en]

Ribonucleotide reductases (RNRs) catalyze the conversion of ribonucleotides to deoxyribonucleotides, and represent the only de novo pathway to provide DNA building blocks. Three different classes of RNR are known, denoted I-III. Class I RNRs are heteromeric proteins built up by α and β subunits and are further divided into different subclasses, partly based on the metal content of the β-subunit. In subclass Ib RNR the β-subunit is denoted NrdF, and harbors a manganese-tyrosyl radical cofactor. The generation of this cofactor is dependent on a flavodoxin-like maturase denoted NrdI, responsible for the formation of an active oxygen species suggested to be either a superoxide or a hydroperoxide. Herein we report on the magnetic properties of the manganese-tyrosyl radical cofactor of Bacillus anthracis NrdF and the redox properties of B. anthracis NrdI. The tyrosyl radical in NrdF is stabilized through its interaction with a ferromagnetically coupled manganese dimer. Moreover, we show through a combination of redox titration and protein electrochemistry that in contrast to hitherto characterized NrdIs, the B. anthracis NrdI is stable in its semiquinone form (NrdIsq) with a difference in electrochemical potential of approximately 110 mV between the hydroquinone and semiquinone state. The under anaerobic conditions stable NrdIsq is fully capable of generating the oxidized, tyrosyl radical-containing form of Mn-NrdF when exposed to oxygen. This latter observation strongly supports that a superoxide radical is involved in the maturation mechanism, and contradicts the participation of a peroxide species. Additionally, EPR spectra on whole cells revealed that a significant fraction of NrdI resides in its semiquinone form in vivo, underscoring that NrdIsq is catalytically relevant.

Place, publisher, year, edition, pages
National Category
Natural Sciences
URN: urn:nbn:se:uu:diva-251765OAI: oai:DiVA.org:uu-251765DiVA: diva2:807712
Available from: 2015-04-24 Created: 2015-04-24 Last updated: 2015-05-05

Open Access in DiVA

No full text

Other links


Search in DiVA

By author/editor
Berggren, Gustav
Natural Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Total: 427 hits
ReferencesLink to record
Permanent link

Direct link