Structure of Plasmodium vivax dihydrofolate reductase determined by homology modeling and molecular dynamics refinement.
The structure of Plasmodium vivax dihydrofolate reductase (PvDHFR), a potentially important target for antimalarial chemotherapy, was determined by means of homology modeling and molecular dynamics refinement. The structure proved to be consistent with DHFRs of known crystal structure. The comparison of the complexes of the antifolate inhibitor pyrimethamine bound at the active sites of PvDHFR and PfDHFR, the related enzyme from Plasmodium falciparum, prospected the possibility of using structure-based drug design to develop inhibitors that are effective against both malarial enzymes. This study constitutes a first step toward understanding of the antifolate-PvDHFR molecular interactions and possible rationalization of resistance in vivax malaria.
Rastelli
Giulio
G
Dipartimento di Scienze Farmaceutiche, Università di Modena e Reggio Emilia, Via Campi 183, 41100 Modena, Italy. rastelli.giulio@unimo.it
Pacchioni
Sara
S
Parenti
Marco Daniele
MD
D000595:Amino Acid Sequence; D000818:Animals; D002645:Chickens; D006801:Humans; D008956:Models, Chemical; D008969:Molecular Sequence Data; D010966:Plasmodium vivax / Q000201:enzymology* / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry* / Q000235:genetics*
D013762:Tetrahydrofolate Dehydrogenase