Change search
ReferencesLink to record
Permanent link

Direct link
Metal use in ribonucleotide reductase R2, di-iron, di-manganese and heterodinuclear-an intricate bioinorganic workaround to use different metals for the same reaction
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
2011 (English)In: METALLOMICS, ISSN 1756-5901, Vol. 3, no 2, 110-120 p.Article, review/survey (Refereed) Published
Abstract [en]

The ferritin-like superfamily comprises of several protein groups that utilize dinuclear metal sites for various functions, from iron storage to challenging oxidations of substrates. Ribonucleotide reductase R2 proteins use the metal site for the generation of a free radical required for the reduction of ribonucleotides to deoxyriboinucleotides, the building blocks of DNA. This ubiquitous and essential reaction has been studied for over four decades and the R2 proteins were, until recently, generally believed to employ the same cofactor and mechanism for radical generation. In this reaction, a stable tyrosyl radical is produced following activation and cleavage of molecular oxygen at a dinuclear iron site in the protein. Discoveries in the last few years have now firmly established that the radical generating reaction is not conserved among the R2 proteins but that different subgroups, that are structurally very similar, instead employ di-manganese or heterodinuclear Mn-Fe cofactors as radical generators. This is remarkable considering that the protein must exercise a strict control over oxygen activation, reactive metal-oxygen intermediate species and the resulting redox potential of the produced radical equivalent. Given the differences in redox properties between Mn and Fe, use of a different metal for this reaction requires associated adaptations of the R2 protein scaffold and the activation mechanism. Further analysis of the differences in protein sequence between R2 subgroups have also led to the discovery of new groups of R2-like proteins with completely different functions, expanding the chemical repertoire of the ferritin-like superfamily. This review describes the discoveries leading up to the identification of the different Mn-containing R2 protein groups and our current understanding of them. Hypotheses regarding the biochemical rationale to develop these chemically complex alternative solutions are also discussed.

Place, publisher, year, edition, pages
2011. Vol. 3, no 2, 110-120 p.
National Category
Biochemistry and Molecular Biology
URN: urn:nbn:se:su:diva-68366DOI: 10.1039/c0mt00095gISI: 000287090500002OAI: diva2:472887
authorCount :1Available from: 2012-01-04 Created: 2012-01-03 Last updated: 2012-01-20Bibliographically approved

Open Access in DiVA

fulltext(4177 kB)14480 downloads
File information
File name FULLTEXT01.pdfFile size 4177 kBChecksum SHA-512
Type fulltextMimetype application/pdf

Other links

Publisher's full text

Search in DiVA

By author/editor
Högbom, Martin
By organisation
Department of Biochemistry and Biophysics
Biochemistry and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar
Total: 14480 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

Altmetric score

Total: 104 hits
ReferencesLink to record
Permanent link

Direct link