Ribonucleotide reductases and radical reactions.
Ribonucleotide reductases (RNRs) catalyse the reduction of ribonucleotides to deoxyribonucleotides. They play a pivotal role in the regulation of DNA synthesis and are targets for antiproliferative drugs. Ribonucleotide reductases are unique enzymes in that they all require a protein radical for activity. Class I nonheme iron RNRs (mammals, plants, Escherichia coli) use a tyrosyl/cysteinyl radical pair, class II adenosylcobalamin RNRs (prokaryotes, archaea) a cysteinyl radical, class III iron-sulphur RNRs (facultative anaerobes) a glycyl radical. Here we describe the reactivity of these radicals with respect to the natural ribonucleotide substrates as well as to a variety of enzyme inhibitors, radical scavengers, nitric oxide, superoxide radicals and substrate analogues.
Laboratoire de Chimie et Biochimie des Centres Rédox Biologiques, CNRS, Université J. Fourier, Grenoble, France. fontecav@cbcrb.ceng.cea.fr
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D001665:Binding Sites / Q000502:physiology; D004247:DNA / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000737:chemistry; D005609:Free Radicals / Q000378:metabolism; D008958:Models, Molecular; D010084:Oxidation-Reduction; D012264:Ribonucleotide Reductases / Q000737:chemistry* / Q000145:classification; D012265:Ribonucleotides / Q000378:metabolism
D004791:Enzyme Inhibitors; D005609:Free Radicals; D012265:Ribonucleotides; D004247:DNA; D012264:Ribonucleotide Reductases