3k7y

Aspartate Aminotransferase of Plasmodium falciparum

spinqualitylabelsall models 3k7y, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3k7y is a 1 chain structure with sequence from Plasmodium falciparum 3D7. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.8Å Ligands: ACT, PLP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function O96142_PLAF7 Publication Abstract from PubMed Aspartate aminotransferases (AspATs; EC 2.6.1.1) catalyze the conversion of aspartate and alpha-ketoglutarate into oxaloacetate and glutamate and are key enzymes in the nitrogen metabolism of all organisms. Recent findings suggest that the plasmodial enzyme [Plasmodium falciparum aspartate aminotransferase (PfAspAT)] may also play a pivotal role in energy metabolism and in the de novo biosynthesis of pyrimidines. However, while PfAspAT is a potential drug target, the high homology between the active sites of currently available AspAT structures hinders the development of specific inhibitors of these enzymes. In this article, we report the X-ray structure of the PfAspAT homodimer at a resolution of 2.8 A. While the overall fold is similar to the currently available structures of other AspATs, the structure presented shows a significant divergence in the conformation of the N-terminal residues. Deletion of these divergent PfAspAT N-terminal residues results in a loss of activity for the recombinant protein, and addition of a peptide containing these 13 N-terminal residues results in inhibition both in vitro and in a lysate isolated from cultured parasites, while the activity of human cytosolic AspAT is unaffected. The finding that the divergent N-terminal amino acids of PfAspAT play a role in catalytic activity indicates that specific inhibition of the enzyme may provide a lead for the development of novel compounds in the treatment of malaria. We also report on the localization of PfAspAT to the parasite cytosol and discuss the implications of the role of PfAspAT in the supply of malate to the parasite mitochondria. Specific Inhibition of the Aspartate Aminotransferase of Plasmodium falciparum.,Wrenger C, Muller IB, Schifferdecker AJ, Jain R, Jordanova R, Groves MR J Mol Biol. 2011 Jan 28;405(4):956-71. Epub 2010 Nov 16. PMID:21087616 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Aspartate aminotransferase 3D structures

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