Malarial Dihydrofolate Reductase as Drug Target

From Proteopedia

proteopedia linkproteopedia link

Introduction

There are currently antimalarial drugs that target the malarial dihydrofolate reductase (DHFR) such as pyrimethamine and cycloguanil. However, the effectiveness of these drugs has decreased because of mutations in the enzyme that have led to drug resistance. New research in drug development now incorporates both the wild-type as well as the quadruple mutant DHFR from the Plasmodium falciparum malarial strain.

spinqualitylabelsall models Crystal structure of Wild-type PfDHFR-TS COMPLEXED WITH NADPH, dUMP AND PYRIMETHAMINE (PDB entry 3QGT) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image Mutant, Drug Resistant PfDHFR The of PfDHFR has four :

N51I, C59R, S108N, and I164L. These mutations caused decreased binding affinities of inhibitors similar to pyrimethamine.