ribonucleotide reductase

Function

• glutathione reductase-dependent reduction of ribonuclotides
  • catalyzes biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides
  • glutaredoxin functions as an electron carrier
• provides precursors for DNA synthesis
  • DNA replication
  • DNA repair

2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H2O
                      <-->
ribonucleoside diphosphate + thioredoxin

Cofactor: binds 2 Fe+2/Fe+3 per subunit (putative)

Structure

• heterodimer of a large (B1) & a small chain (B2)
• 2 distinct regulatory sites have been defined:
  • specificity site, which controls substrate specificity
  • activity site which regulates overall catalytic activity
• substrate-binding catalytic site, located on B1, is formed only in the presence of the second subunit B2

Compartment

cytoplasm

Pathology

• ribonucleotide reductase is thought to mediate pathogenesis of the immunodeficiency of
  • adenosine deaminase deficiency
  • purine nucleoside phosphorylase deficiency
• deoxynucleotides that accumulate in lymphoid cells are thought to feed-back inhibit ribonucleotide reductase, preventing DNA replication & cell proliferation

More general terms

• oxidoreductase
• nuclear protein
• multisubunit protein

More specific terms

• ribonucleotide diphosphate reductase