an enzyme involved in DNA replication that provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides. Belongs to the ribonucleoside diphosphate reductase large chain family. Heterodimer of a large and a small subunit. Heterodimer with small subunit RRM2 or RRM2B. The heterodimer with RRM2 has higher catalytic activity than the heterodimer with RRM2B. Under complex allosteric control mediated by deoxynucleoside triphosphates and ATP binding to separate specificity and activation sites on the M1 subunit. The type of nucleotide bound at the specificity site determines substrate preference. It seems probable that ATP makes the enzyme reduce CDP and UDP, dGTP favors ADP reduction and dTTP favors GDP reduction. Stimulated by ATP and inhibited by dATP binding to the activity site. Two distinct regulatory sites have been defined: the specificity site, which controls substrate specificity, and the activity site which regulates overall catalytic activity. A substrate-binding catalytic site, located on M1, is formed only in the presence of the second subunit M2. The level of the enzyme activity is closely correlated with the growth rate of a cell and appears to vary with the cell cycle. Patients with advanced non-small cell lung cancer responded favorably to gemcitabine. Note: This description may include information from UniProtKB.
Protein type: Nucleotide Metabolism - purine; Nucleotide Metabolism - pyrimidine; Other Amino Acids Metabolism - glutathione; Oxidoreductase; EC 220.127.116.11; DNA replication
Molecular Function: protein binding; ATP binding; ribonucleoside-diphosphate reductase activity
Biological Process: pyrimidine base metabolic process; retina development in camera-type eye; nucleobase, nucleoside and nucleotide interconversion; nucleobase, nucleoside and nucleotide metabolic process; cell proliferation in forebrain; male gonad development; deoxyribonucleotide biosynthetic process; protein heterotetramerization; mitotic cell cycle; response to ionizing radiation; DNA replication
SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.