The reduction of ribonucleotides catalyzed by the enzyme ribonucleotide reductase

This work is devoted to the study of the radical catalytic pathway for the ribonucleotide reduction process assisted by ribonucleotide reductase. The present study is directed toward the investigation of one of the most controversial steps in the reduction pathway - the elimination of the 2' hydroxyl group from the ribonucleotide. Several groups have made different proposals for this step, which all fit available experimental data; however, so far, it has not been possible to demonstrate clearly which is the correct pathway for the elimination. Here, we resort to high-level quantum mechanical calculations to analyze the energetics of the proposed mechanisms, as well as to propose alternative pathways, and evaluate their feasibility, according to the observed kinetics of the enzyme and other existing experimental data. Our study shows that the elimination occurs via two different simultaneous acid-/base-catalyzed pathways, depending on the protonation state of one key active site amino acid, Glu441. Electronic Supplementary Material. Supplementary material is available for this article if you access the article at http: //dx.doi.org/10.1007/s00214-002-0393-3.