Ribonucleotide Reduction

Florence Kowalczyk Gleason, University of Minnesota, St. Paul, Minnesota, USA

Published online: May 2005

DOI: 10.1038/npg.els.0003873

Ribonucleotide reductase is an essential enzyme that supplies the precursors for DNA synthesis. Three classes of reductases are known. These differ in primary structure, substrate and cofactor requirements, but all use a protein radical to catalyse reduction.

Keywords: deoxyribonucleotide; protein radicals; DNA synthesis

Scheme 1. Reduction of ribonucleotide to 2¢-deoxyribonucleotide catalysed by ribonucleotide reductase.
Scheme 2. Proposed mechanism for ribonucleotide reductase. Adapted with permission from Mao et al. (1992) Copyright © 1992 American Chemical Society.
Figure 1. Tyrosyl radical and di-iron centre in E. coli R2 subunit. Adapted from Nordlund et al. (1990).
Figure 2. Structure of the R2 dimer. The C- chain of one subunit is shown in blue and the other in yellow. The iron atoms in each subunit are in orange. The van der Waals surface of Tyr122 is in blue. Reproduced with permission from Nordlund et al. (1990).
Figure 3. Structure of the R1/B domain. The first half of the barrel is yellow, and the second half is green. The connecting loop is magenta. The three conserved cysteines at the active site are seen inside the barrel. Roduced with permission from Uhlin and Eklund (1994).
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 References
    Björklund S, Skogman E and Thelander L (1992) An S phase-specific release from a transcriptional block regulates the expression of mouse ribonucleotide reductase R2 subunit. EMBO Journal 11: 4953–4959.
    Ekberg M, Sahlin M, Eriksson M and Sjöberg BM (1996) Two conserved tyrosine residues in protein R1 participate in an intramolecular electron transfer in ribonucleotide reductase. Journal of Biological Chemistry 271: 20655–20659.
    Eriksson M, Uhlin U and Ramaswamy S et al. (1997) Binding of allosteric effectors to ribonucleotide reductase protein R1: reduction of active-site cysteines promotes substrate binding. Structure 5: 1077–1092.
    Kauppi B, Nielsen BA and Ramaswamy S et al. (1996) The three-dimensional structure of mammalian ribonucleotide reductase protein R2 reveals a more-accessible iron-radical site than Escherichia coli R2. Journal of Molecular Biology 262: 706–720.
    Logan DT, Andersson J, Sjöberg B-M and Nordlund P (1999) A glycyl radical site in the crystal structure of a class III ribonucleotide reductase. Science 283: 1499–1504.
    Mao SS, Holler TP and Xu GX et al. (1992) A model for the role of multiple cysteine residues involved in ribonucleotide reduction: amazing and still confusing. Biochemistry 31: 9733–9743.
    Nordlund P, Sjöberg BM and Eklund H (1990) Three-dimensional structure of the free radical protein of ribonucleotide reductase. Nature 345: 593–598.
    Sintchak MD, Arjara G, Kellogg BA, Stubbe JA and Drennan CL (2002) The crystal structure of class II ribonucleotide reductase reveals how an allosterically regulated monomer mimics a dimer. Nature Structural Biology 9: 293–300.
    Tanaka H, Arakawa H and Yamaguchi T et al. (2000) A ribonucleotide reductase gene involved in a p53-dependent cell-cycle checkpoint for DNA damage. Nature 404: 42–49.
    Uhlin U and Eklund H (1994) Structure of ribonucleotide reductase protein R1. Nature 370: 533–539.
 Further Reading
    Eklund H, Uhlin U, Färnegårdh M, Logan DT and Nordlund P (2001) Structure and function of the radical enzyme ribonucleotide reductase. Progress in Biophysics and Molecular Biology 77: 177–268.
    Elledge SJ, Zhou Z, Allen JB and Navas TA (1993) DNA damage and cell cycle regulation of ribonucleotide reductase. BioEssays 15: 333–339.
    Gräslund A and Sahlin M (1996) Electron paramagnetic resonance and nuclear magnetic resonance studies of class I ribonucleotide reductase. Annual Review of Biophysics and Biomolecular Structure 25: 259–286.
    Greenberg GR and Hilfinger JM (1996) Regulation of synthesis of ribonucleotide reductase and relationship to DNA replication in various systems. Progress in Nucleic Acid Research and Molecular Biology 53: 345–395.
    Jordan A, Torrents E, Sala I, Hellman U, Gibert I and Reichard P (1999) Ribonucleotide reduction in Pseudomonas species: simultaneous presence of active enzymes from different classes. Journal of Bacteriology 181: 3874–3980.
    book Karlsson M and Sahlin M (1997) "Microbial ribonucleotide reductases – essential and diverse". In: Winkelman G and Carrano CJ (eds) Transition Metals in Microbial Metabolism pp. 435–470. The Netherlands: Harwood Academic.
    Licht S, Gerfen GJ and Stubbe J (1996) Thiyl radicals in ribonucleotide reductases. Science 271: 477–481.
    Poole AM, Logan DT and Sjöberg B-M (2002) The evolution of the ribonucleotide reductases: much ado about oxygen. Journal of Molecular Evolution 55: 180–196.
    Sjöberg BM (1997) Ribonucleotide reductase – A group of enzymes with different metallosites and a similar reaction mechanism. Structure and Bonding 88: 138–173.
    Stubbe J and van der Donk WA (1995) Ribonucleotide reductases: radical enzymes with suicidal tendencies. Chemistry and Biology 2: 793–801.

Related Sub-Topics:

DNA Structure and Function | Enzymes: Structure and Action Mechanism | Nucleic Acids: Structure, Function, Metabolism
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Article Title: Ribonucleotide Reduction
 
How to Cite close
Gleason, Florence Kowalczyk(May 2005) Ribonucleotide Reduction. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0003873]