2y8c

Plasmodium falciparum dUTPase in complex with a trityl ligand

spinqualitylabelsall models 2y8c, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2y8c is a 3 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 2.1Å Ligands: DUQ, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q8II92_PLAF7 Publication Abstract from PubMed We report a series of beta-branched acyclic tritylated deoxyuridine analogues as inhibitors of Plasmodium falciparum deoxyuridine-5'-triphosphate nucleotidohydrolase (PfdUTPase), an enzyme involved in nucleotide metabolism that acts as first line of defence against uracil incorporation into DNA. Compounds were assayed against both PfdUTPase and intact parasites showing a correlation between enzyme inhibition and cellular assays. beta-Branched acyclic uridine analogues described here showed equal or slightly better potency and selectivity compared with previously reported analogues. The best inhibitor gave a K(i) of 0.5 muM against PfdUTPase with selectivity greater than 200-fold compared to the corresponding human enzyme and sub-micromolar growth inhibition of P. falciparum (EC(50) 0.6 muM). A crystal structure of the complex of PfdUTPase with one of the inhibitors shows that this acyclic derivative binds to the active site in a similar manner to that previously reported for a tritylated cyclic deoxyuridine derivative. beta-Branched acyclic nucleoside analogues as inhibitors of Plasmodium falciparum dUTPase.,Baragana B, McCarthy O, Sanchez P, Bosch-Navarrete C, Kaiser M, Brun R, Whittingham JL, Roberts SM, Zhou XX, Wilson KS, Johansson NG, Gonzalez-Pacanowska D, Gilbert IH Bioorg Med Chem. 2011 Apr 1;19(7):2378-91. Epub 2011 Feb 17. PMID:21411327 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also DUTPase 3D structures

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