Crystallographic and docking studies of purine nucleoside phosphorylase from Mycobacterium tuberculosis

Rodrigo G Ducati; Luiz A Basso; Diógenes S Santos; Walter F de Azevedo Jr

doi:10.1016/j.bmc.2010.05.009

Crystallographic and docking studies of purine nucleoside phosphorylase from Mycobacterium tuberculosis

Bioorg Med Chem. 2010 Jul 1;18(13):4769-74. doi: 10.1016/j.bmc.2010.05.009. Epub 2010 May 10.

Authors

Rodrigo G Ducati¹, Luiz A Basso, Diógenes S Santos, Walter F de Azevedo Jr

Affiliation

¹ Centro de Pesquisas em Biologia Molecular e Funcional, Instituto de Pesquisas Biomédicas, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Avenida Ipiranga 6681/92-A, 90619-900 Porto Alegre, RS, Brazil.

PMID: 20570524
DOI: 10.1016/j.bmc.2010.05.009

Abstract

This work describes for the first time the structure of purine nucleoside phosphorylase from Mycobacterium tuberculosis (MtPNP) in complex with sulfate and its natural substrate, 2'-deoxyguanosine, and its application to virtual screening. We report docking studies of a set of molecules against this structure. Application of polynomial empirical scoring function was able to rank docking solutions with good predicting power which opens the possibility to apply this new criterion to analyze docking solutions and screen small-molecule databases for new chemical entities to inhibit MtPNP.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Binding Sites
Catalytic Domain
Computer Simulation
Crystallography, X-Ray
Deoxyguanosine / chemistry
Deoxyguanosine / pharmacology
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology
Mycobacterium tuberculosis / enzymology*
Purine-Nucleoside Phosphorylase / chemistry*
Purine-Nucleoside Phosphorylase / metabolism
Small Molecule Libraries / chemistry
Small Molecule Libraries / pharmacology
Sulfates / chemistry
Sulfates / pharmacology

Substances

Enzyme Inhibitors
Small Molecule Libraries
Sulfates
Purine-Nucleoside Phosphorylase
Deoxyguanosine