Inhibiting Mycobacterium tuberculosis CoaBC by targeting a new allosteric site
Inhibiting Mycobacterium tuberculosis CoaBC by targeting a new allosteric site
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通过靶向新的变构位点抑制结核分枝杆菌 CoaBC
DOI：
10.1101/870154
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Mendes V
中科院分区：
文献类型：
--
作者：
Mendes V
Coenzyme A (CoA) is a fundamental co-factor for all life, involved in numerous metabolic pathways and cellular processes, and its biosynthetic pathway has raised substantial interest as a drug target against multiple pathogens includingMycobacterium tuberculosis. The biosynthesis of CoA is performed in five steps, with the second and third steps being catalysed in the vast majority of prokaryotes, includingM. tuberculosis, by a single bifunctional protein, CoaBC. Depletion of CoaBC was found to be bactericidal inM. tuberculosis. Here we report the first structure of a full-length CoaBC, from the model organismMycobacterium smegmatis, describe how it is organised as a dodecamer and regulated by CoA thioesters. A high-throughput biochemical screen focusing on CoaB identified two inhibitors with different chemical scaffolds. Hit expansion led to the discovery of potent and selective inhibitors ofM. tuberculosisCoaB, which we show to bind to a cryptic allosteric site within CoaB.
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DOI：
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发表时间：
1987
期刊：
The Journal of biological chemistry
影响因子：
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作者：
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通讯作者：
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影响因子：
5.6
作者：
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影响因子：
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作者：
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DOI：
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发表时间：
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期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
Kupke, T
通讯作者：
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