title: Molecular modeling and dynamics studies of purine nucleoside phosphorylase from Bacteroides fragilis.
abstract: Purine nucleoside phosphorylase (PNP) catalyzes the reversible phosphorolysis of N-ribosidic bonds of purine nucleosides and deoxynucleosides, except adenosine, to generate ribose 1-phosphate and the purine base. This work describes for the first time a structural model of PNP from Bacteroides fragilis (Bf). We modeled the complexes of BfPNP with six different ligands in order to determine the structural basis for specificity of these ligands against BfPNP. Comparative analysis of the model of BfPNP and the structure of HsPNP allowed identification of structural features responsible for differences in the computationally determined ligand affinities. The molecular dynamics (MD) simulation was assessed to evaluate the overall stability of the BfPNP model. The superposition of the final onto the initial minimized structure shows that there are no major conformational changes from the initial model, which is consistent with the relatively low root mean square deviation (RMSD). The results indicate that the structure of the model was stable during MD, and does not exhibit loosely structured loop regions or domain terminals.
authors.affiliation: Laboratório de Bioquímica Estrutural, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Ivani
authors.initials: I
authors.lastname: Pauli
authors.forename: Luis Fernando Saraiva Macedo
authors.initials: LF
authors.lastname: Timmers
authors.forename: Rafael Andrade
authors.initials: RA
authors.lastname: Caceres
authors.forename: Luiz Augusto
authors.initials: LA
authors.lastname: Basso
authors.forename: Diógenes Santiago
authors.initials: DS
authors.lastname: Santos
authors.forename: Walter Filgueira
authors.initials: WF
authors.lastname: de Azevedo
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001441:Bacteroides fragilis / Q000201:enzymology* / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D001667:Binding, Competitive; D003198:Computer Simulation; D004795:Enzyme Stability; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011683:Purine-Nucleoside Phosphorylase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D001426:Bacterial Proteins; D008024:Ligands; D011683:Purine-Nucleoside Phosphorylase