3ozf

Crystal Structure of Plasmodium falciparum Hypoxanthine-Guanine-Xanthine Phosphoribosyltransferase in complex with hypoxanthine

spinqualitylabelsall models 3ozf, resolution 1.94Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3ozf is a 4 chain structure with sequence from Plafg. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: HPA, MG, PO4, POP Related: 3ozg Gene: LACZ (PLAFG) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [HGXR_PLAFG] Converts guanine to guanosine monophosphate, and hypoxanthine to inosine monophosphate. Transfers the 5-phosphoribosyl group from 5-phosphoribosylpyrophosphate onto the purine. Works with guanine, hypoxanthine and xanthine. Plays a central role in the generation of purine nucleotides through the purine salvage pathway. Publication Abstract from PubMed Plasmodium falciparum, the primary cause of deaths from malaria, is a purine auxotroph and relies on hypoxanthine salvage from the host purine pool. Purine starvation as an antimalarial target has been validated by inhibition of purine nucleoside phosphorylase. Hypoxanthine depletion kills Plasmodium falciparum in cell culture and in Aotus monkey infections. Hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRT) from P. falciparum is required for hypoxanthine salvage by forming inosine 5'-monophosphate, a branchpoint for all purine nucleotide synthesis in the parasite. Here, we present a class of HGXPRT inhibitors, the acyclic immucillin phosphonates (AIPs), and cell permeable AIP prodrugs. The AIPs are simple, potent, selective, and biologically stable inhibitors. The AIP prodrugs block proliferation of cultured parasites by inhibiting the incorporation of hypoxanthine into the parasite nucleotide pool and validates HGXPRT as a target in malaria. Acyclic Immucillin Phosphonates: Second-Generation Inhibitors of Plasmodium falciparum Hypoxanthine- Guanine-Xanthine Phosphoribosyltransferase.,Hazleton KZ, Ho MC, Cassera MB, Clinch K, Crump DR, Rosario I Jr, Merino EF, Almo SC, Tyler PC, Schramm VL Chem Biol. 2012 Jun 22;19(6):721-30. PMID:22726686 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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