2blc

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spinqualitylabelsall models 2blc, resolution 2.25Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

SP21 DOUBLE MUTANT P. VIVAX DIHYDROFOLATE REDUCTASE IN COMPLEX WITH DES-CHLOROPYRIMETHAMINE

Overview

Pyrimethamine (Pyr) targets dihydrofolate reductase of Plasmodium vivax, (PvDHFR) as well as other malarial parasites, but its use as antimalarial, is hampered by the widespread high resistance. Comparison of the crystal, structures of PvDHFR from wild-type and the Pyr-resistant (SP21, Ser-58, --> Arg + Ser-117 --> Asn) strain as complexes with NADPH and Pyr or its, analog lacking p-Cl (Pyr20) clearly shows that the steric conflict arising, from the side chain of Asn-117 in the mutant enzyme, accompanied by the, loss of binding to Ser-120, is mainly responsible for the reduction in, binding of Pyr. Pyr20 still effectively inhibits both the wild-type and, SP21 proteins, and the x-ray structures of these complexes show how Pyr20, fits into both active sites without steric strain. ... [(full description)]

About this Structure

2BLC is a [Single protein] structure of sequence from [Plasmodium vivax] with NDP, CP7 and MES as [ligands]. Active as [[1]], with EC number [1.5.1.3]. Full crystallographic information is available from [OCA].

Reference

Crystal structure of dihydrofolate reductase from Plasmodium vivax: pyrimethamine displacement linked with mutation-induced resistance., Kongsaeree P, Khongsuk P, Leartsakulpanich U, Chitnumsub P, Tarnchompoo B, Walkinshaw MD, Yuthavong Y, Proc Natl Acad Sci U S A. 2005 Sep 13;102(37):13046-51. Epub 2005 Aug 31. PMID:16135570

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