Ribonucleotide reductases.
Ribonucleotide reductases (RNRs) transform RNA building blocks to DNA building blocks by catalyzing the substitution of the 2'OH-group of a ribonucleotide with a hydrogen by a mechanism involving protein radicals. Three classes of RNRs employ different mechanisms for the generation of the protein radical. Recent structural studies of members from each class have led to a deeper understanding of their catalytic mechanism and allosteric regulation by nucleoside triphosphates. The main emphasis of this review is on regulation of RNR at the molecular and cellular level. Conformational transitions induced by nucleotide binding determine the regulation of substrate specificity. An intricate interplay between gene activation, enzyme inhibition, and protein degradation regulates, together with the allosteric effects, enzyme activity and provides the appropriate amount of deoxynucleotides for DNA replication and repair. In spite of large differences in the amino acid sequences, basic structural features are remarkably similar and suggest a common evolutionary origin for the three classes.
Nordlund
Pär
P
Division of Biophysics and 2Division of Biochemistry, Medical Nobel Institute, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-17177 Stockholm, Sweden. par.nordlund@mbb.ki.se
Reichard
Peter
P
D000494:Allosteric Regulation; D000818:Animals; D001665:Binding Sites; D019143:Evolution, Molecular; D005609:Free Radicals / Q000378:metabolism; D005656:Fungal Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D011487:Protein Conformation; D012264:Ribonucleotide Reductases / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D015533:Transcriptional Activation
D005609:Free Radicals; D005656:Fungal Proteins; D012264:Ribonucleotide Reductases