Ribonucleotide reductases: substrate specificity by allostery.
Ribonucleotide reductases catalyze in all living organisms the production of deoxynucleotides from ribonucleotides. A single enzyme provides a balanced supply of the four dNTPs required for DNA replication. Three different but related classes of enzymes are known. Each class catalyzes the same chemistry using a common radical mechanism involving a thiyl radical of the enzyme but the three classes employ different mechanisms for the generation of the radical. For each class a common allosteric mechanism with ATP and dNTPs as effectors directs the substrate specificity of the enzymes ensuring the appropriate balance of the four dNTPs for DNA replication. Recent crystallographic studies of the catalytic subunits from each class in combination with allosteric effectors, with and without cognate substrates, delineated the structural changes caused by effector binding that direct the specificity of the enzymes towards reduction of the appropriate substrate.
Reichard
Peter
P
Department of Biochemistry, Medical Nobel Institute, Karolinska Institutet, Stockholm 17177, Sweden. peter.reichard@ki.se
D000494:Allosteric Regulation; D002384:Catalysis; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000201:enzymology; D011487:Protein Conformation; D012313:RNA / Q000378:metabolism*; D012264:Ribonucleotide Reductases / Q000737:chemistry* / Q000145:classification / Q000378:metabolism; D013379:Substrate Specificity; D020124:Thermotoga maritima / Q000201:enzymology
D012313:RNA; D012264:Ribonucleotide Reductases