Discovery of a compound that acts as a bacterial PyrG (CTP synthase) inhibitor
| Autor: | Hatsumi Nasu, Eiko Namba, Makoto Yamashita, Tatsuhiko Yoshida, Osamu Ubukata |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Microbiology (medical)
Staphylococcus aureus Pyrimidine Cytidine Triphosphate ATPase Uridine Triphosphate Microbial Sensitivity Tests medicine.disease_cause Microbiology Haemophilus influenzae Inhibitory Concentration 50 chemistry.chemical_compound Bacterial Proteins medicine Humans Carbon-Nitrogen Ligases Enzyme Inhibitors Respiratory Tract Infections Acivicin Adenosine Triphosphatases Bacteria biology General Medicine Benzoic Acid biology.organism_classification Antimicrobial Anti-Bacterial Agents Metabolic pathway Streptococcus pneumoniae Biochemistry chemistry biology.protein |
| Zdroj: | Journal of Medical Microbiology. 61:1280-1285 |
| ISSN: | 1473-5644 0022-2615 |
| DOI: | 10.1099/jmm.0.046052-0 |
| Popis: | PyrG (CTP synthase) catalyses the conversion of UTP to CTP, an essential step in the pyrimidine metabolic pathway in a variety of bacteria, including those causing community-acquired respiratory tract infections (RTIs). In this study, a luminescence-based ATPase assay of PyrG was developed and used to evaluate the inhibitory activity of 2-(3-[3-oxo-1,2-benzisothiazol-2(3H)-yl]phenylsulfonylamino) benzoic acid (compound G1). Compound G1 inhibited PyrG derived from Streptococcus pneumoniae with a 50 % inhibitory concentration value of 0.091 µM, and the inhibitory activity of compound G1 was 13 times higher than that of acivicin (1.2 µM), an established PyrG inhibitor. The results of saturation transfer difference analysis using nuclear magnetic resonance spectroscopy suggested that these compounds compete with ATP and/or UTP for binding to Strep. pneumoniae PyrG. Finally, compound G1 was shown to have antimicrobial activity against several different bacteria causing RTIs, such as Staphylococcus aureus and Haemophilus influenzae, suggesting that it is a prototype chemical compound that could be harnessed as an antimicrobial drug with a novel structure to target bacterial PyrG. |
| Databáze: | OpenAIRE |
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