title: Transition state analogue discrimination by related purine nucleoside phosphorylases.
abstract: Transition state analogues of PNP, the Immucillins and DADMe-Immucillins, were designed to match transition state features of bovine and human PNPs, respectively. The inhibitors with or without the hydroxyl and hydroxymethyl groups of the substrate demonstrate that inhibitor geometry mimicking that of the transition state confers binding affinity discrimination. This finding is remarkable since crystallographic analysis indicates complete conservation of active site residues and contacts to ligands in human and bovine PNPs.
authors.affiliation: Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Erika A
authors.initials: EA
authors.lastname: Taylor Ringia
authors.forename: Peter C
authors.initials: PC
authors.lastname: Tyler
authors.forename: Gary B
authors.initials: GB
authors.lastname: Evans
authors.forename: Richard H
authors.initials: RH
authors.lastname: Furneaux
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Murkin
authors.forename: Vern L
authors.initials: VL
authors.lastname: Schramm
mesh_terms: D000818:Animals; D001149:Arsenates / Q000737:chemistry; D002417:Cattle; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D004912:Erythrocytes / Q000201:enzymology; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D011485:Protein Binding; D011684:Purine Nucleosides / Q000737:chemistry; D011683:Purine-Nucleoside Phosphorylase / Q000037:antagonists & inhibitors / Q000737:chemistry*; D011744:Pyrimidinones / Q000737:chemistry; D011759:Pyrrolidines / Q000737:chemistry
chemical_list: D001149:Arsenates; C508755:DADMe-immucillin H; D004791:Enzyme Inhibitors; D011684:Purine Nucleosides; D011744:Pyrimidinones; D011759:Pyrrolidines; C113101:forodesine; D011683:Purine-Nucleoside Phosphorylase