Carba-sugars Activate the glmS-Riboswitch of Staphylococcus aureus
Carba-sugars Activate the glmS-Riboswitch of Staphylococcus aureus
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DOI：
10.1021/cb200016d
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发表时间：
2011-07-01
影响因子：
4
通讯作者：
Mayer, Guenter
中科院分区：
文献类型：
--
作者：
Luense, Christina E.;Schmidt, Magnus S.;Mayer, Guenter
glms -核糖体开关在核糖体开关家族中是独一无二的，因为它代表了一种代谢物依赖的核糖体酶，在识别氨基葡萄糖-6-磷酸后进行自裂解。glms -核糖开关位于参与细胞壁生物合成的细菌基因的5'-非翻译区。因此，这种核糖开关代表了开发新抗生素的一个有希望的靶点。我们描述了金黄色葡萄球菌的代谢产物依赖的glms -核糖体开关，病理相关的和耐万古霉素的金黄色葡萄球菌，并发现和合成了一种碳糖，其在调节核糖体开关活性方面的作用与天然代谢物氨基葡萄糖-6-磷酸相似。该化合物为开发具有新作用模式的抗生素提供了有价值的先导结构。
The glmS-riboswitch is unique among riboswitch families as it represents a metabolite-dependent ribozyme that undergoes self-cleavage upon recognition of glucosamin-6-phosphate. The glmS-riboswitch is located in the 5'-untranslated region of bacterial genes involved in cell wall biosynthesis. Therefore, this riboswitch represents a promising target for developing new antibiotics. We describe the metabolite-dependent glmS-riboswitch of,pathologically relevant and vancomycin-resistant Staphylococcus aureus and the discovery and synthesis of a carba-sugar with potency similar to that of the native metabolite glucosamine-6-phosphate in modulating riboswitch activity. This compound represents a valuable lead structure for the development of antibiotics with a novel mode of action.