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A metal-binding site in the catalytic subunit of anaerobic ribonucleotide reductase
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
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2003 In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, Vol. 100, no 7, 3826-3831 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2003. Vol. 100, no 7, 3826-3831 p.
URN: urn:nbn:se:su:diva-23371OAI: diva2:191544
Part of urn:nbn:se:su:diva-251Available from: 2004-09-22 Created: 2004-09-22Bibliographically approved
In thesis
1. Allosteric Regulation and Radical Transfer in Ribonucleotide Reductase
Open this publication in new window or tab >>Allosteric Regulation and Radical Transfer in Ribonucleotide Reductase
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The stability of biological life over time requires that the integrity of the genetic material of an organism, the genome, be maintained as it is passed on from one generation to the next. All known cellular life has DNA-based genomes, which are duplicated before each cell division in a process called replication. During and after DNA replication, the integrity of the genetic information is maintained by various proofreading and DNA repair mechanisms. The accuracy of DNA replication and repair is affected by DNA precursor pool imbalances. Feedback regulation of the enzymes involved in DNA precursor biosynthesis has evolved in parallel with the DNA replication and repair system in order to ensure stable precursor pools.

Ribonucleotide reductase (RNR), an enzyme that irreversibly reduces ribonucleotides into deoxyribonucleotides, is a key component in the regulation of the DNA precursor pools. It has sophisticated allosteric regulatory mechanisms that govern both overall activity and substrate specificity, responding to the cellular concentrations of ATP and of the triphosphate forms of the product deoxyribonucleotides, the final DNA precursors.

Using X-ray crystallography we have solved several structures of two ribonucleotide reductases, an anaerobic (class III) enzyme from Bacteriophage T4 and a coenzyme B12-dependent (class II) enzyme from Thermotoga maritima, in complex with various nucleotides and cofactors. The structural information reveals a complete molecular mechanism for the allosteric substrate specificity regulation of class II RNRs which, due to structural homology, is likely also to be valid for the aerobic class I RNRs. The work on the class III RNRs has produced a partial mechanism for the specificity regulation of this class. Both mechanisms utilize Loop 2, a conserved structural element, in the transmission of the allosteric signal.

The discovery of a metal binding domain in the anaerobic RNRs and details of coenzyme B12 binding shed more light on generation and transfer of the protein based radicals used in the reduction reaction.

Place, publisher, year, edition, pages
Stockholm: Institutionen för biokemi och biofysik, 2004. 57 p.
allosteric regulation, substrate specificity, ribonucleotide reductase, radical
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
urn:nbn:se:su:diva-251 (URN)91-7265-931-9 (ISBN)
Public defence
2004-10-13, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 12 A, Stockholm, 14:00 (English)
Available from: 2004-09-22 Created: 2004-09-22 Last updated: 2009-04-06Bibliographically approved

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