New catalytic mechanism for human purine nucleoside phosphorylase.
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.
Canduri
Fernanda
F
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
Fadel
Valmir
V
Basso
Luiz Augusto
LA
Palma
Mário Sérgio
MS
Santos
Diógenes Santiago
DS
de Azevedo
Walter Filgueira
WF
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
D004791:Enzyme Inhibitors; D011684:Purine Nucleosides; D011744:Pyrimidinones; D011758:Pyrroles; C113101:forodesine; D011683:Purine-Nucleoside Phosphorylase; D000212:Acyclovir