Change search
ReferencesLink to record
Permanent link

Direct link
Diversity in Overall Activity Regulation of Ribonucleotide Reductase
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. (Anders Hofer)
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. (Anders Hofer)
Show others and affiliations
2015 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 290, no 28, 17339-17348 p.Article in journal (Refereed) Published
Abstract [en]

Ribonucleotide reductase (RNR) catalyzes the reduction of ribonucleotides to the corresponding deoxyribonucleotides, which are used as building blocks for DNA replication and repair. This process is tightly regulated via two allosteric sites, the specificity site (s-site) and the overall activity site (a-site). The a-site resides in an N-terminal ATP cone domain that binds dATP or ATP and functions as an on/off switch, whereas the composite s-site binds ATP, dATP, dTTP, or dGTP and determines which substrate to reduce. There are three classes of RNRs, and class I RNRs consist of different combinations of α and β subunits. In eukaryotic and Escherichia coli class I RNRs, dATP inhibits enzyme activity through the formation of inactive α6 and α4β4 complexes, respectively. Here we show that the Pseudomonas aeruginosa class I RNR has a duplicated ATP cone domain and represents a third mechanism of overall activity regulation. Each α polypeptide binds three dATP molecules, and the N-terminal ATP cone is critical for binding two of the dATPs because a truncated protein lacking this cone could only bind dATP to its s-site. ATP activates the enzyme solely by preventing dATP from binding. The dATP-induced inactive form is an α4 complex, which can interact with β2 to form a non-productive α4β2 complex. Other allosteric effectors induce a mixture of α2 and α4 forms, with the former being able to interact with β2 to form active α2β2 complexes. The unique features of the P. aeruginosa RNR are interesting both from evolutionary and drug discovery perspectives.

Place, publisher, year, edition, pages
2015. Vol. 290, no 28, 17339-17348 p.
National Category
Biochemistry and Molecular Biology
URN: urn:nbn:se:umu:diva-109543DOI: 10.1074/jbc.M115.649624ISI: 000357730900029PubMedID: 25971975OAI: diva2:857888
Swedish Research CouncilThe Kempe FoundationsCarl Tryggers foundation
Available from: 2015-09-30 Created: 2015-09-30 Last updated: 2015-10-27Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Jonna, Venkateswara RaoRofougaran, RezaJohansson, SamuelBrännström, KristofferHofer, Anders
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
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: 112 hits
ReferencesLink to record
Permanent link

Direct link