title: New catalytic mechanism for human purine nucleoside phosphorylase.
abstract: Human purine nucleoside phosphorylase has been submitted to intensive structure-based design of inhibitors, most of them using low-resolution structures of human PNP. Recently, several structures of human PNP have been reported, which allowed redefinition of the active site and understanding of the structural basis for inhibition of PNP by acyclovir and immucillin-H. Based on previously solved human PNP structures, we proposed here a new catalytic mechanism for human PNP, which is supported by crystallographic studies and explains previously determined kinetic data.
authors.affiliation: Programa de Pós-graduação em Biofísica Molecular, Departamento de Física, UNESP, São José do Rio Preto, SP 15054-000, Brazil. canduri@webmail.ibilce.unesp.br
authors.forename: Fernanda
authors.initials: F
authors.lastname: Canduri
authors.forename: Valmir
authors.initials: V
authors.lastname: Fadel
authors.forename: Luiz Augusto
authors.initials: LA
authors.lastname: Basso
authors.forename: Mário Sérgio
authors.initials: MS
authors.lastname: Palma
authors.forename: Diógenes Santiago
authors.initials: DS
authors.lastname: Santos
authors.forename: Walter Filgueira
authors.initials: WF
authors.lastname: de Azevedo
mesh_terms: D000212:Acyclovir / Q000494:pharmacology; D001665:Binding Sites; D002384:Catalysis; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D011684:Purine Nucleosides; D011683:Purine-Nucleoside Phosphorylase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D011744:Pyrimidinones / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D011684:Purine Nucleosides; D011744:Pyrimidinones; D011758:Pyrroles; C113101:forodesine; D011683:Purine-Nucleoside Phosphorylase; D000212:Acyclovir