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重组肺炎链球菌UDP-葡萄糖焦磷酸化酶抑制剂的筛选试验

Screening assay for inhibitors of a recombinant Streptococcus pneumoniae UDP-glucose pyrophosphorylase.

作者信息

Zavala Agustín, Kovacec Verónica, Levín Gustavo, Moglioni Albertina, Miranda María Victoria, García Ernesto, Bonofiglio Laura, Mollerach Marta

机构信息

a Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Microbiología , Inmunología y Biotecnología, Cátedra de Microbiología , Buenos Aires , Argentina.

b Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Microbiología , Inmunología y Biotecnología, Cátedra de Biotecnología , Buenos Aires , Argentina.

出版信息

J Enzyme Inhib Med Chem. 2017 Dec;32(1):203-207. doi: 10.1080/14756366.2016.1247055.

DOI:10.1080/14756366.2016.1247055
PMID:28114831
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6009895/
Abstract

The UDP-glucose pyrophosphorylase of Streptococcus pneumoniae (GalU) 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 GalU was 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.

摘要

肺炎链球菌的UDP-葡萄糖焦磷酸化酶（GalU）是荚膜多糖生物合成绝对必需的，荚膜多糖是肺炎球菌的关键毒力因子。由于真核酶与原核酶完全不相关，我们提出GalU酶是对抗肺炎球菌疾病的关键靶点。一种重组GalU被过量表达并纯化。开发了一种快速、灵敏且易于操作的酶活性测定方法。该测定方法适用于筛选化学文库以寻找GalU抑制剂。这项工作是探索新型抗肺炎球菌药物的重要一步。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40cb/6009895/211b647e51dc/IENZ_A_1247055_F0002_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40cb/6009895/2185885e809d/IENZ_A_1247055_F0001_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40cb/6009895/211b647e51dc/IENZ_A_1247055_F0002_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40cb/6009895/2185885e809d/IENZ_A_1247055_F0001_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40cb/6009895/211b647e51dc/IENZ_A_1247055_F0002_B.jpg

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本文引用的文献

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Pneumococcal surface proteins: when the whole is greater than the sum of its parts.肺炎球菌表面蛋白：整体大于部分之和。
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