title: Screening assay for inhibitors of a recombinant Streptococcus pneumoniae UDP-glucose pyrophosphorylase.
abstract: The UDP-glucose pyrophosphorylase of Streptococcus pneumoniae (GalUSpn) is absolutely required for the biosynthesis of capsular polysaccharide, the sine qua non virulence factor of pneumococcus. Since the eukaryotic enzymes are completely unrelated to their prokaryotic counterparts, we propose that the GalU enzyme is a critical target to fight the pneumococcal disease. A recombinant GalUSpnwas overexpressed and purified. An enzymatic assay that is rapid, sensitive and easy to perform was developed. This assay was appropriate for screening chemical libraries for searching GalU inhibitors. This work represents a fundamental step in the exploration of novel antipneumococcal drugs.
authors.affiliation: a Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Microbiología , Inmunología y Biotecnología, Cátedra de Microbiología , Buenos Aires , Argentina.
authors.forename: Agustín
authors.initials: A
authors.lastname: Zavala
authors.affiliation: a Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Microbiología , Inmunología y Biotecnología, Cátedra de Microbiología , Buenos Aires , Argentina.
authors.forename: Verónica
authors.initials: V
authors.lastname: Kovacec
authors.affiliation: b Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Microbiología , Inmunología y Biotecnología, Cátedra de Biotecnología , Buenos Aires , Argentina.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Levín
authors.affiliation: c Departamento de Farmacología, Facultad de Farmacia y Bioquímica , Cátedra de Química Medicinal, Universidad de Buenos Aires , Buenos Aires , Argentina.
authors.forename: Albertina
authors.initials: A
authors.lastname: Moglioni
authors.affiliation: b Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Microbiología , Inmunología y Biotecnología, Cátedra de Biotecnología , Buenos Aires , Argentina.
authors.forename: María Victoria
authors.initials: MV
authors.lastname: Miranda
authors.affiliation: d Centro de Investigaciones Biológicas, CSIC and CIBER de Enfermedades Respiratorias (CIBERES) , Madrid , Spain.
authors.forename: Ernesto
authors.initials: E
authors.lastname: García
authors.affiliation: a Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Microbiología , Inmunología y Biotecnología, Cátedra de Microbiología , Buenos Aires , Argentina.
authors.forename: Laura
authors.initials: L
authors.lastname: Bonofiglio
authors.affiliation: a Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Microbiología , Inmunología y Biotecnología, Cátedra de Microbiología , Buenos Aires , Argentina.
authors.forename: Marta
authors.initials: M
authors.lastname: Mollerach
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011994:Recombinant Proteins / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000201:enzymology*; D013329:Structure-Activity Relationship; D005957:UTP-Glucose-1-Phosphate Uridylyltransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; D005957:UTP-Glucose-1-Phosphate Uridylyltransferase
keywords: Antibacterial target; UTP:glucose 1-phosphate uridylyltransferase; pneumococcus; virulence inhibitors