Radical Enzymes

Britt‐Marie Sjöberg, Stockholm University, Stockholm, Sweden
Margareta Sahlin, Stockholm University, Stockholm, Sweden

Published online: September 2005

DOI: 10.1038/npg.els.0003889

Radical enzymes harbour a stable free radical in their polypeptide chain, which participates in catalysis. A growing number of enzymes are known to require a posttranslationally generated free radical for their proper functioning. The radical is generally used to remove a hydrogen atom from an unreactive position in the substrate, activating the substrate to undergo difficult chemistry. Some radical enzymes have unexpectedly been found to harbour a stable radical on an amino acid side-chain that is distinct from the side-chains of the active site region; during catalysis, the stable free radical interacts with the active site via electron or radical transfer and between turnovers it serves as a radical sink.

Keywords: tyrosyl radical; glycyl radical; cysteinyl radical; ribonucleotide reductase

Figure 1. Class I ribonucleotide reductase (RNR). (a) Proposed long-range radical transfer pathway and (b) radical reaction mechanism (structure and numbering refer to class Ia RNR from E. coli). Names in blue identify residues in protein R1, and names in red identify residues in R2. Tyr356 is in a flexible C-terminal part of R2 and not visible in the electron density map.
Figure 2. Galactose oxidase. (a) Structure of the active site region and (b) proposed radical reaction mechanism (structure and numbering refer to GO from Dactylium dendroides). The copper ion is shown in green and electron density at the vacant position is modelled as acetate in red.
Figure 3. Prostaglandin H synthase. (a) Structure of the active site region and (b) proposed radical reaction mechanism (structure and numbering refer to PGHS-1 from Ovis aries). The haem is shown in yellow, and the aspirin analogue 2-bromoacetoxybenzoic acid and the aspirin antagonist salicylic acid in red. AA, arachidonic acid; PP, protoporphyrin, PGG2, prostaglandin G2; PGH2, prostaglandin H2.
Figure 4. Class III ribonucleotide reductase. (a) Structure of the active site region of the G580A mutant enzyme and (b) proposed radical reaction mechanism of the wild-type enzyme (structure and numbering refer to class III RNR from bacteriophage T4).
Figure 5. Pyruvate formate–lyase. (a) Structure of the active site region including the substrates pyruvate and CoA and (b) proposed radical reaction mechanism (structure and numbering refer to PFL from E. coli).
Figure 6. Class II ribonucleotide reductase. Structure of the active site region of the L. leichmannii enzyme. The proposed radical reaction mechanism for class II RNR is identical to the mechanism of class I RNR in Figure 1b, with L. leichmannii residues Cys119, Asn406, Cys408, Glu410 and Cys419, corresponding to Cys225, Asn437, Cys439, Glu441 and Cys462 in Figure 1b.
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 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 & Molecular Biology 77: 177–268.
    Fontecave M, Atta M and Mulliez E (2004) S-adenosylmethionine: nothing goes to waste. Trends in Biochemical Sciences 29: 243–249.
    Frey PA and Magnusson OT (2003) S- Adenosylmethionine: a wolf in sheep's clothing, or a rich man's adenosylcobalamin?. Chemical Reviews 103: 2129–2148.
    Himo F and Siegbahn PEM (2003) Quantum chemical studies of radical-containing enzymes. Chemical Reviews 103: 2421–2456.
    Jordan A and Reichard P (1998) Ribonucleotide reductases. Annual Review of Biochemistry 67: 71–98.
    Knappe J and Wagner AFV (2001) Stable glycyl radical from pyruvate formate-lyase and ribonucleotide reductase (III). Advances in Protein Chemistry 58: 277–315.
    Kolberg M, Strand KR, Graff P and Andersson KK (2004) Structure, function, and mechanism of Ribonucleotide reductases. Biochimica Biophysica Acta 1699: 1–34.
    Rogers MS and Dooley DM (2003) Copper-tyrosyl radical enzymes. Current Opinion in Chemical Biology 7: 189–196.
    Rouzer CA and Marnett LJ (2003) Mechanism of free radical oxygenation of polyunsaturated fatty acids by cyclooxygenases. Chemical Reviews 103: 2239–2304.
    Sjöberg BM and Sahlin M (2002) Thiols in redox mechanism of ribonucleotide reductase. Methods in Enzymology 348: 1–21.
    Stubbe JA (2003) Di-iron-tyrosyl radical ribonucleotide reductases. Current Opinion in Chemical Biology 7: 183–188.

Related Sub-Topics:

Protein Structure | Enzymes: Structure and Action Mechanism
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Article Title: Radical Enzymes
 
How to Cite close
Sjöberg, Britt‐Marie, and Sahlin, Margareta(Sep 2005) Radical Enzymes. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0003889]