The use of thiols by ribonucleotide reductase.
Ribonucleotide reductase (RNR) catalyzes the rate-limiting de novo synthesis of 2'-deoxyribonucleotides from the corresponding ribonucleotides and thereby provides balanced deoxyribonucleotide pools required for error-free DNA replication and repair. The essential role of RNR in DNA synthesis and the use of DNA as genetic 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 cysteines, thiyl radicals, and thiol 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.
Holmgren
Arne
A
Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden. arne.holmgren@ki.se
Sengupta
Rajib
R
D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D002384:Catalysis / Q000187:drug effects; D006801:Humans; D008954:Models, Biological; D012264:Ribonucleotide Reductases / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology*; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D013439:Sulfhydryl Reagents / Q000737:chemistry / Q000494:pharmacology
D000970:Antineoplastic Agents; D013438:Sulfhydryl Compounds; D013439:Sulfhydryl Reagents; D012264:Ribonucleotide Reductases