title: Crystal structure of calf spleen purine nucleoside phosphorylase complexed to a novel purine analogue.
abstract: The combined use of a rapid virtual screen of a small fragment library together with a single point enzyme assay has been used for the discovery of novel PNP inhibitors. The availability of readily soakable crystals of bovine PNP has allowed the approach to be experimentally validated by determining the crystal structure of one of the inhibitor-PNP complexes. Comparison of the experimentally determined binding mode with that predicted by the virtual screening shows them to be similar. This represents a starting point for the growth of the ligand into a higher affinity inhibitor.
authors.affiliation: Instituto de Física de São Carlos, Universidade de São Paulo, Physics and Informatics, Av. Trabalhador Saocarlense 400, Centro CP 369, 13560-970 Sao Carlos, São Paulo, Brazil. hmuniz.pereira@gmail.com
authors.forename: H M
authors.initials: HM
authors.lastname: Pereira
authors.forename: V
authors.initials: V
authors.lastname: Berdini
authors.forename: A
authors.initials: A
authors.lastname: Cleasby
authors.forename: R C
authors.initials: RC
authors.lastname: Garratt
mesh_terms: D000818:Animals; D002417:Cattle; D018360:Crystallography, X-Ray; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D011487:Protein Conformation; D011683:Purine-Nucleoside Phosphorylase / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D011687:Purines / Q000737:chemistry* / Q000494:pharmacology; D013154:Spleen / Q000201:enzymology*
chemical_list: D004791:Enzyme Inhibitors; D011687:Purines; D011683:Purine-Nucleoside Phosphorylase