1onf | pdb_00001onf

Crystal structure of Plasmodium falciparum Glutathione reductase

spinqualitylabelsall models 1onf, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1onf is a 1 chain structure with sequence from Plasmodium falciparum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.6Å Ligands: FAD Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GSHR_PLAFK Maintains high levels of reduced glutathione in the cytosol (By similarity). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The malarial parasite Plasmodium falciparum is known to be sensitive to oxidative stress, and thus the antioxidant enzyme glutathione reductase (GR; NADPH+GSSG+H(+) <==> NADP(+)+2 GSH) has become an attractive drug target for antimalarial drug development. Here, we report the 2.6A resolution crystal structure of P.falciparum GR. The homodimeric flavoenzyme is compared to the related human GR with focus on structural aspects relevant for drug design. The most pronounced differences between the two enzymes concern the shape and electrostatics of a large (450A(3)) cavity at the dimer interface. This cavity binds numerous non-competitive inhibitors and is a target for selective drug design. A 34-residue insertion specific for the GRs of malarial parasites shows no density, implying that it is disordered. The precise location of this insertion along the sequence allows us to explain the deleterious effects of a mutant in this region and suggests new functional studies. To complement the structural comparisons, we report the relative susceptibility of human and plasmodial GRs to a series of tricyclic inhibitors as well as to peptides designed to interfere with protein folding and dimerization. Enzyme-kinetic studies on GRs from chloroquine-resistant and chloroquine-sensitive parasite strains were performed and indicate that the structure reported here represents GR of P.falciparum strains in general and thus is a highly relevant target for drug development. Glutathione reductase of the malarial parasite Plasmodium falciparum: crystal structure and inhibitor development.,Sarma GN, Savvides SN, Becker K, Schirmer M, Schirmer RH, Karplus PA J Mol Biol. 2003 May 9;328(4):893-907. PMID:12729762 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Glutathione Reductase

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