EC 1.17.4.2 - Ribonucleoside-triphosphate reductase (thioredoxin)

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IntEnz Enzyme Nomenclature
EC 1.17.4.2

Names

Accepted name:
ribonucleoside-triphosphate reductase (thioredoxin)
Other names:
2'-deoxyribonucleoside-triphosphate:oxidized-thioredoxin 2'-oxidoreductase
ribonucleotide reductase [ambiguous]
Systematic name:
2'-deoxyribonucleoside-triphosphate:thioredoxin-disulfide 2'-oxidoreductase

Reaction

Cofactor

Comments:

The enzyme, characterized from the bacterium Lactobacillus leichmannii, is similar to class II ribonucleoside-diphosphate reductase (cf. EC 1.17.4.1). However, it is specific for the triphosphate versions of its substrates. The enzyme contains an adenosylcobalamin cofactor that is involved in generation of a transient thiyl (sulfanyl) radical on a cysteine residue. This radical attacks the substrate, forming a ribonucleotide 3'-radical, followed by water loss to form a ketyl (α-oxoacyl) radical. The ketyl radical is reduced to 3'-keto-deoxynucleotide concomitant with formation of a disulfide anion radical between two cysteine residues. A proton-coupled electron-transfer from the disulfide radical to the substrate generates a 3'-deoxynucleotide radical, and the the final product is formed when the hydrogen atom that was initially removed from the 3'-position of the nucleotide by the thiyl radical is returned to the same position. The disulfide bridge is reduced by the action of thioredoxin. cf. EC 1.1.98.6, ribonucleoside-triphosphate reductase (formate).

Links to other databases

Enzymes and pathways: NC-IUBMB , BRENDA , ExplorEnz , ENZYME@ExPASy , KEGG , MetaCyc , UniPathway
Protein domains and families: PROSITE:PDOC00665
Structural data: CSA , EC2PDB
Gene Ontology: GO:0008998
CAS Registry Number: 9068-66-0
UniProtKB/Swiss-Prot: (14) [show] [UniProt]

References

  1. Blakley, R.L.
    Cobamides and ribonucleotide reduction. I. Cobamide stimulation of ribonucleotide reduction in extracts of Lactobacillus leichmannii.
    J. Biol. Chem. 240: 2173-2180 (1965). [PMID: 14299643]
  2. Goulian, M. and Beck, W.S.
    Purification and properties of cobamide-dependent ribonucleotide reductase from Lactobacillus leichmannii.
    J. Biol. Chem. 241: 4233-4242 (1966). [PMID: 5924645]
  3. Stubbe, J., Ackles, D., Segal, R., Blakley, R. L.
    On the mechanism of ribonucleoside triphosphate reductase from Lactobacillus leichmannii. Evidence for 3' C--H bond cleavage.
    J. Biol. Chem. 256: 4843-4846 (1981). [PMID: 7014560]
  4. Ashley, G. W., Harris, G., Stubbe, J.
    The mechanism of Lactobacillus leichmannii ribonucleotide reductase. Evidence for 3' carbon-hydrogen bond cleavage and a unique role for coenzyme B12.
    J. Biol. Chem. 261: 3958-3964 (1986). [PMID: 3512563]
  5. Lawrence, C. C., Stubbe, J.
    The function of adenosylcobalamin in the mechanism of ribonucleoside triphosphate reductase from Lactobacillus leichmannii.
    Curr Opin Chem Biol 2: 650-655 (1998). [PMID: 9818192]
  6. Licht, S. S., Booker, S., Stubbe, J.
    Studies on the catalysis of carbon-cobalt bond homolysis by ribonucleoside triphosphate reductase: evidence for concerted carbon-cobalt bond homolysis and thiyl radical formation.
    Biochemistry 38: 1221-1233 (1999). [PMID: 9930982]

[EC 1.17.4.2 created 1972, modified 2017]