Ribonucleotide reductase: no longer confusing but still amazing

Ribonucleotide reductases catalyze the conversion of all nucleotides to deoxynucleotides, an essential step in DNA biosynthesis. Evidence will be presented, using rapid-freeze quench (RFQ) EPR -methods that a thiyl radical is generated in a kinetically competent fashion. Further evidence will be presented using RFQ EPR methods and 2' fluoromethylidene-nucleotides with RNRs that the function of the thiyl radical is to abstract a 3' hydrogen atom of the substrate. The first evidence for 3'-substrate derived radical will be presented. Thus, while the subtle details of the nucleotide reduction may never be known, the studies presented provide substantial support for the model proposed by Stubbe and co-workers in 1990 for a general mechanism of nucleotide reduction, subsequent to the generation of a transient protein radical.