Structural model of the Plasmodium falciparum Thioredoxin reductase:a novel target for antimalarial drugs

Abstract

Background: Malaria, a scourge of mankind, imposes a huge socioeconomic burden in tropicalcountries. Emergence of multi-drug resistant malarial parasites impels us to explore novel drugtargets. Thioredoxin reductase is a promising antimalarial drug target.Methods: The Thioredoxin reductase enzyme of Plasmodium falciparum was characterized insilico and protein disorder was predicted using available online tools. Since the crystal structure ofThioredoxin reductase of P. falciparum is not yet available, its three-dimensional structure wasconstructed by homology modeling using the high-resolution Thioredoxin reductase type 2 ofmouse as a template. Obtained model was further refined by Molecular Dynamics (MD).Results: The model was stable during the simulation with the equilibrium root mean square deviation(RMSD) value of 1.2 Å. Stereochemical evaluation revealed that 99.1% residues of the constructedmodel lie in the most favoured and allowed regions, thus, indicating a good quality model.Conclusion: Results of this study will provide an insight into the structure of the Thioredoxinreductase of malarial parasite and aid in rational drug designing.

Keywords

• Homology modeling
• malaria
• oxidative stress
• Plasmodium
• redox system
• Thioredoxin reductase