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Biophys Chem. 2009 Jun;142(1-3):7-16. doi: 10.1016/j.bpc.2009.02.006. Epub 2009 Feb 26.

Molecular modeling, dynamics and docking studies of purine nucleoside phosphorylase from Streptococcus pyogenes.

Author information

1
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

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.

PMID:
19282092
DOI:
10.1016/j.bpc.2009.02.006
[Indexed for MEDLINE]

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