title: Crystal structure of human PNP complexed with guanine.
abstract: Purine nucleoside phosphorylase (PNP) catalyzes the phosphorolysis of the N-ribosidic bonds of purine nucleosides and deoxynucleosides. PNP is a target for inhibitor development aiming at T-cell immune response modulation and has been submitted to extensive structure-based drug design. More recently, the 3-D structure of human PNP has been refined to 2.3A resolution, which allowed a redefinition of the residues involved in the substrate-binding sites and provided a more reliable model for structure-based design of inhibitors. This work reports crystallographic study of the complex of Human PNP:guanine (HsPNP:Gua) solved at 2.7A resolution using synchrotron radiation. Analysis of the structural differences among the HsPNP:Gua complex, PNP apoenzyme, and HsPNP:immucillin-H provides explanation for inhibitor binding, refines the purine-binding site, and can be used for future inhibitor design.
authors.affiliation: Departamento de Física, UNESP, São José do Rio Preto, SP 15054-000, Brazil. walterfa@df.ibilce.unesp.br
authors.forename: Walter Filgueira
authors.initials: WF
authors.lastname: de Azevedo
authors.forename: Fernanda
authors.initials: F
authors.lastname: Canduri
authors.forename: Denis Marangoni
authors.initials: DM
authors.lastname: dos Santos
authors.forename: José Henrique
authors.initials: JH
authors.lastname: Pereira
authors.forename: Márcio Vinicius
authors.initials: MV
authors.lastname: Bertacine Dias
authors.forename: Rafael Guimarães
authors.initials: RG
authors.lastname: Silva
authors.forename: Maria Anita
authors.initials: MA
authors.lastname: Mendes
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
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D003460:Crystallization / Q000379:methods*; D003461:Crystallography / Q000379:methods*; D004789:Enzyme Activation; D006147:Guanine / Q000737:chemistry*; D006801:Humans; D046911:Macromolecular Substances; D008958:Models, Molecular; D010710:Phosphates / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D011683:Purine-Nucleoside Phosphorylase / Q000737:chemistry*; D012996:Solutions; D013379:Substrate Specificity; D013722:Teprotide; D014867:Water / Q000737:chemistry*
chemical_list: D046911:Macromolecular Substances; D010710:Phosphates; D012996:Solutions; D014867:Water; D006147:Guanine; D013722:Teprotide; D011683:Purine-Nucleoside Phosphorylase