title: Ribonucleotide reductase as a target to control apicomplexan diseases.
abstract: Malaria is caused by species in the apicomplexan genus Plasmodium, which infect hundreds of millions of people each year and kill close to one million. While malaria is the most notorious of the apicomplexan-caused diseases, other members of eukaryotic phylum Apicomplexa are responsible for additional, albeit less well-known, diseases in humans, economically important livestock, and a variety of other vertebrates. Diseases such as babesiosis (hemolytic anemia), theileriosis and East Coast Fever, cryptosporidiosis, and toxoplasmosis are caused by the apicomplexans Babesia, Theileria, Cryptosporidium and Toxoplasma, respectively. In addition to the loss of human life, these diseases are responsible for losses of billions of dollars annually. Hence, the research into new drug targets remains a high priority. Ribonucleotide reductase (RNR) is an essential enzyme found in all domains of life. It is the only means by which de novo synthesis of deoxyribonucleotides occurs, without which DNA replication and repair cannot proceed. RNR has long been the target of antiviral, antibacterial and anti-cancer therapeutics. Herein, we review the chemotherapeutic methods used to inhibit RNR, with particular emphasis on the role of RNR inhibition in Apicomplexa, and in light of the novel RNR R2_e2 subunit recently identified in apicomplexan parasites.
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, 21201, USA.
authors.forename: James B
authors.initials: JB
authors.lastname: Munro
authors.forename: Joana C
authors.initials: JC
authors.lastname: Silva
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology / Q000627:therapeutic use; D016782:Apicomplexa / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D008969:Molecular Sequence Data; D058990:Molecular Targeted Therapy; D010271:Parasites / Q000187:drug effects / Q000201:enzymology; D011528:Protozoan Infections / Q000188:drug therapy / Q000517:prevention & control*; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000145:classification / Q000378:metabolism
chemical_list: D000981:Antiprotozoal Agents; D012264:Ribonucleotide Reductases