ribonucleotide reductase B1 subunit; M1 subunit; ribonucleoside diphosphate reductase large subunit (RRM1, RR1)

Function

• provides precursors for DNA synthesis
• catalyzes biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides
• under complex allosteric control mediated by binding of deoxynucleoside triphosphates & ATP to binding sites on the M1 subunit
• ribonucleotide reductase is a heterodimer of a large (M1) & a small chain (M2)
• interacts with RRM2B
• Genetic information processing, DNA replication
• 2 distinct regulatory sites have been defined:
  • the specificity site, which controls substrate specificity,
  • activity site which regulates overall catalytic activity
• substrate-binding catalytic site, located on M1, is formed only in the presence of the 2nd subunit M2

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

Structure

• belongs to the ribonucleoside diphosphate reductase large chain family
• contains 1 ATP-cone domain

Compartment

cytoplasm

Expression

• level of the enzyme activity is closely correlated with the growth rate of a cell & appears to vary with the cell cycle

Pathology

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

More general terms

• protein subunit
• oligomerizing protein

Component of

• ribonucleotide reductase

Database

• UniProt: http://www.uniprot.org/uniprot/P23921.html
• OMIM: https://mirror.omim.org/entry/180410