English

Abstract

Malaria is a global health problem caused by Plasmodium parasites. Glutathione S-transferase (GST) is involved in the conjugation of glutathione to drugs and toxic compounds. It is postulated that GST plays an important role in the development of drug resistance. The three-dimensional (3D) structure of Plasmodium falciparum GST (PfGST) has been solved and previous work indicates that the PfGST cannot be assigned to any of the known GST classes. We performed sequence analyses, structural modeling and alignment of GSTs from Plasmodium to known structures of the GST from other organisms to classify PfGST into a GST family. Sequence alignments using ClustalW, motif analysis using MEME, and phylogenetic analysis using MEGA4, of Plasmodium GSTs and 38 other GST sequences were done. The alignments and motifs show a close relationship to the alpha and sigma class of GSTs. The phylogenetic analysis places the Plasmodium GSTs in the sigma class. A comparison of PfGST with known structures of GSTs reveals high structural similarity to the sigma class GST, in particular within the H-site and C-terminus of the protein. These findings allow PfGST to be classified into the sigma class GSTs. These data may open new avenues for the development of novel antimalarials.