title: Molecular modeling, dynamics and docking studies of purine nucleoside phosphorylase from Streptococcus pyogenes.
abstract: Purine Nucleoside Phosphorylase (PNP) catalyzes the reversible phosphorolysis of N-glycosidic bonds of purine nucleosides and deoxynucleosides, except for adenosine, to generate ribose 1-phosphate and the purine base. PNP has been submitted to intensive structural studies. This work describes for the first time a structural model of PNP from Streptococcus pyogenes (SpPNP). We modeled the complexes of SpPNP with six different ligands in order to determine the structural basis for specificity of these ligands against SpPNP. Molecular dynamics (MD) simulations were performed in order to evaluate the overall stability of SpPNP model. The analysis of the MD simulation was assessed mainly by principal component analysis (PCA) to explore the trimeric structure behavior. Structural comparison, between SpPNP and human PNP, was able to identify the main features responsible for differences in ligand-binding affinities, such as mutation in the purine-binding site and in the second phosphate-binding site. The PCA analysis suggests a different behavior for each subunit in the trimer structure.
authors.affiliation: Faculdade de Biociências, Laboratório de Bioquímica Estrutural, Instituto Nacional de Ciência e Tecnologia em Tuberculose, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre-RS, Brazil. luis@azevedolab.net
authors.forename: Luis Fernando Saraiva Macedo
authors.initials: LF
authors.lastname: Timmers
authors.forename: Rafael Andrade
authors.initials: RA
authors.lastname: Caceres
authors.forename: Raquel
authors.initials: R
authors.lastname: Dias
authors.forename: Luiz Augusto
authors.initials: LA
authors.lastname: Basso
authors.forename: Diogenes Santiago
authors.initials: DS
authors.lastname: Santos
authors.forename: Walter Filgueira
authors.initials: WF
authors.lastname: de Azevedo
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D003198:Computer Simulation; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011683:Purine-Nucleoside Phosphorylase / Q000737:chemistry* / Q000378:metabolism; D016415:Sequence Alignment; D013297:Streptococcus pyogenes / Q000201:enzymology*
chemical_list: D008024:Ligands; D011683:Purine-Nucleoside Phosphorylase