Computational analysis of binding between malarial dihydrofolate reductases and anti-folates.

ABSTRACT:

Background

Plasmodium falciparum readily develops resistance to the anti-folates pyrimethamine and proguanil via a characteristic set of mutations in the dihydrofolate reductase (PfDHFR) gene that leads to reduced competitive drug binding at the enzyme's active site. Analogous mutations can be found in the DHFR gene in isolates of Plasmodium vivax (PvDHFR) although anti-folates have not been widely used for the treatment of this infection. Here the interactions between DHFR inhibitors and modelled structures of the DHFR enzymes of Plasmodium malariae (PmDHFR) and Plasmodium ovale (PoDHFR) are described, along with an investigation of the effect of recently reported mutations within PmDHFR.

Methods

DHFR models for PmDHFR and PoDHFR were constructed using the solved PfDHFR-TS

SUBMITTER: Choowongkomon K 

PROVIDER: S-EPMC2838911 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature