The use of thiols by ribonucleotide reductase

Ribonucletide reductase (RNR) catalyzes the rate-limiting de novo synthesis of 2 deoxyribonucleotides from the corresponding riboncleotides and thereby provides balanced deoxyribonucleoticle pools required for error-free DNA replication and repair The essential role of RNR in DNA synthesis and the use of DNA as genen, material has made it an important target for the development of anticancer and antiviral agents The most well known feature of the universal RNR reaction in all kingdoms of life is the involvement of protein free radicals Redox-active cystemes thiyl radicals and and redox proteins of the thioredoxin superfamily play major roles in the catalytic mechanism The involvement of cysteine residues in catalysis is common to all three classes of RNR Taking account of the recent progress in this field of research this review focuses on the use of thiols in the redox mechanism of RNR enzymes (C) 2010 Elsevier Inc All rights reserved