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.