title: Plasmodium falciparum Thioredoxin Reductase (PfTrxR) and Its Role as a Target for New Antimalarial Discovery.
abstract: The growing resistance to current antimalarial drugs is a major concern for global public health. The pressing need for new antimalarials has led to an increase in research focused on the Plasmodium parasites that cause human malaria. Thioredoxin reductase (TrxR), an enzyme needed to maintain redox equilibrium in Plasmodium species, is a promising target for new antimalarials. This review paper provides an overview of the structure and function of TrxR, discusses similarities and differences between the thioredoxin reductases (TrxRs) of different Plasmodium species and the human forms of the enzyme, gives an overview of modeling Plasmodium infections in animals, and suggests the role of Trx functions in antimalarial drug resistance. TrxR of Plasmodium falciparum is a central focus of this paper since it is the only Plasmodium TrxR that has been crystallized and P. falciparum is the species that causes most malaria cases. It is anticipated that the information summarized here will give insight and stimulate new directions in which research might be most beneficial.
authors.affiliation: College of Sciences and Mathematics, Auburn University, Auburn, AL 36849, USA. ans0038@auburn.edu.|Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849, USA. ans0038@auburn.edu.
authors.forename: Sara E
authors.initials: SE
authors.lastname: McCarty
authors.affiliation: Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849, USA. ans0038@auburn.edu.|College of Agriculture, Auburn University, Auburn, AL 36849, USA. ans0038@auburn.edu.
authors.forename: Amanda
authors.initials: A
authors.lastname: Schellenberger
authors.affiliation: Department of Chemistry and Biochemistry, Auburn University, Auburn, AL 36849, USA. goodwdc@auburn.edu.
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Goodwin
authors.affiliation: Department of Chemistry and Biochemistry, Auburn University, Auburn, AL 36849, USA. rfn0001@tigermail.auburn.edu.
authors.forename: Ngolui Rene
authors.initials: NR
authors.lastname: Fuanta
authors.affiliation: National Center for Natural Products Research and Department of BioMolecular Sciences, School of Pharmacy, University of Mississippi, Oxford, MS 38677, USA. btekwani@olemiss.edu.
authors.forename: Babu L
authors.initials: BL
authors.lastname: Tekwani
authors.affiliation: Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849, USA. aic0001@auburn.edu.
authors.forename: Angela I
authors.initials: AI
authors.lastname: Calderón
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use; D004351:Drug Resistance / Q000187:drug effects; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D058990:Molecular Targeted Therapy; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology; D013329:Structure-Activity Relationship; D013880:Thioredoxin-Disulfide Reductase / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D000962:Antimalarials; D013880:Thioredoxin-Disulfide Reductase
keywords: Plasmodium falciparum; animal models; malaria; thioredoxin reductase