title: Structures of human purine nucleoside phosphorylase complexed with inosine and ddI.
abstract: Human purine nucleoside phosphorylase (PNP) is a ubiquitous enzyme which plays a key role in the purine salvage pathway, and PNP deficiency in humans leads to an impairment of T-cell function, usually with no apparent effect on B-cell function. PNP is highly specific for 6-oxopurine nucleosides and exhibits negligible activity for 6-aminopurine nucleosides. The catalytic efficiency for inosine is 350,000-fold greater than for adenosine. Adenine nucleosides and nucleotides are deaminated by adenosine deaminase and AMP deaminase to their corresponding inosine derivatives which, in turn, may be further degraded. Here we report the crystal structures of human PNP in complex with inosine and 2('),3(')-dideoxyinosine, refined to 2.8A resolution using synchrotron radiation. The present structures provide explanation for ligand binding, refine 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.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Canduri
authors.forename: Denis Marangoni
authors.initials: DM
authors.lastname: dos Santos
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: Walter Filgueira
authors.initials: WF
authors.lastname: de Azevedo
authors.forename: Diógenes Santiago
authors.initials: DS
authors.lastname: Santos
mesh_terms: D001665:Binding Sites; D018360:Crystallography, X-Ray; D016049:Didanosine / Q000737:chemistry*; D006801:Humans; D066298:In Vitro Techniques; D007288:Inosine / Q000737:chemistry*; D008024:Ligands; D046911:Macromolecular Substances; D008958:Models, Molecular; D011487:Protein Conformation; D011683:Purine-Nucleoside Phosphorylase / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry
chemical_list: D008024:Ligands; D046911:Macromolecular Substances; D011994:Recombinant Proteins; D007288:Inosine; D011683:Purine-Nucleoside Phosphorylase; D016049:Didanosine