Umeå University's logo

umu.sePublications
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
A glutaredoxin domain fused to the radical-generating subunit of ribonucleotide reductase (RNR) functions as an efficient RNR reductant
Show others and affiliations
2018 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 293, no 41, p. 15889-15900Article in journal (Refereed) Published
Abstract [en]

Class I ribonucleotide reductase (RNR) consists of a catalytic subunit (NrdA) and a radical-generating subunit (NrdB) that together catalyze reduction of ribonucleotides to their corresponding deoxyribonucleotides. NrdB from the firmicute Facklamia ignava is a unique fusion protein with N-terminal add-ons of a glutaredoxin (Grx) domain followed by an ATP-binding domain, the ATP cone. Grx, usually encoded separately from the RNR operon, is a known RNR reductant. We show that the fused Grx domain functions as an efficient reductant of the F. ignava class I RNR via the common dithiol mechanism and, interestingly, also via a monothiol mechanism, although less efficiently. To our knowledge, a Grx that uses both of these two reaction mechanisms has not previously been observed with a native substrate. The ATP cone is in most RNRs an N-terminal domain of the catalytic subunit. It is an allosteric on/off switch promoting ribonucleotide reduction in the presence of ATP and inhibiting RNR activity in the presence of dATP. We found that dATP bound to the ATP cone of F. ignava NrdB promotes formation of tetramers that cannot form active complexes with NrdA. The ATP cone bound two dATP molecules but only one ATP molecule. F. ignava NrdB contains the recently identified radical-generating cofactor MnIII/MnIV. We show that NrdA from F. ignava can form a catalytically competent RNR with the MnIII/MnIV-containing NrdB from the flavobacterium Leeuwenhoekiella blandensis. In conclusion, F. ignava NrdB is fused with a Grx functioning as an RNR reductant and an ATP cone serving as an on/off switch.

Place, publisher, year, edition, pages
American Society for Biochemistry and Molecular Biology, 2018. Vol. 293, no 41, p. 15889-15900
Keywords [en]
ribonucleotide reductase, allosteric regulation, oxidation-reduction (redox), radical, manganese, ATP-cone, dATP inhibition, dithiol-monothiol, glutaredoxin, tetramers
National Category
Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:umu:diva-153125DOI: 10.1074/jbc.RA118.004991ISI: 000447256000013PubMedID: 30166338Scopus ID: 2-s2.0-85054896844OAI: oai:DiVA.org:umu-153125DiVA, id: diva2:1262487
Available from: 2018-11-12 Created: 2018-11-12 Last updated: 2023-03-24Bibliographically approved

Open Access in DiVA

fulltext(3995 kB)176 downloads
File information
File name FULLTEXT01.pdfFile size 3995 kBChecksum SHA-512
983aa3bd9db902cb8eaaeb9b50e7495790861a5c69aacfe5565defbf06035d831bb70e7cb5bf5d8758bba743ff0722e5cf346513d444d49501291e75c462b579
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMedScopus

Authority records

Hofer, Anders

Search in DiVA

By author/editor
Hofer, AndersSjöberg, Britt-Marie
By organisation
Department of Medical Biochemistry and Biophysics
In the same journal
Journal of Biological Chemistry
Biochemistry and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar
Total: 176 downloads
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

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 365 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