RIBONUCLEOTIDE REDUCTASES

Ribonucleotide reductases provide the building blocks for DNA replicat ion in all living cells. Three different classes of enzymes use protei n free radicals to activate the substrate. Aerobic class I enzymes gen erate a tyrosyl radical with an iron-oxygen center and dioxygen, class II enzymes employ adenosylcobalamin, and the anaerobic class III enzy mes generate a glycyl radical from S-adenosylmethionine and an iron-su lfur cluster. The X-ray structure of the class I Escherichia coli enzy me, including forms that bind substrate and allosteric effecters, conf irms previous models of catalytic and allosteric mechanisms. This stru cture suggests considerable mobility of the protein during catalysis a nd, together with experiments involving site-directed mutants, suggest s a mechanism for radical transfer from one subunit to the other. Desp ite large differences between the classes, common catalytic and allost eric mechanisms, as well as retention of critical residues in the prot ein sequence, suggest a similar tertiary structure and a common origin during evolution. One puzzling aspect is that some organisms contain the genes for several different reductases.