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DOI | 10.1038/ncomms15298 |
Synthetic ligands for PreQ(1) riboswitches provide structural and mechanistic insights into targeting RNA tertiary structure | |
Connelly, Colleen M.1; 39;Amare, Adrian R.2 | |
2019-04-02 | |
发表期刊 | NATURE COMMUNICATIONS
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ISSN | 2041-1723 |
出版年 | 2019 |
卷号 | 10 |
文章类型 | Article |
语种 | 英语 |
国家 | USA; Japan |
英文摘要 | Riboswitches are naturally occurring RNA aptamers that regulate gene expression by binding to specific small molecules. Riboswitches control the expression of essential bacterial genes and are important models for RNA-small molecule recognition. Here, we report the discovery of a class of synthetic small molecules that bind to PreQ(1) riboswitch aptamers. These molecules bind specifically and reversibly to the aptamers with high affinity and induce a conformational change. Furthermore, the ligands modulate riboswitch activity through transcriptional termination despite no obvious chemical similarity to the cognate ligand. X-ray crystallographic studies reveal that the ligands share a binding site with the cognate ligand but make different contacts. Finally, alteration of the chemical structure of the ligand causes changes in the mode of RNA binding and affects regulatory function. Thus, target- and structure-based approaches can be used to identify and understand the mechanism of synthetic ligands that bind to and regulate complex, folded RNAs. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000462986000005 |
WOS关键词 | BINDING SMALL MOLECULES ; LONG NONCODING RNAS ; PURINE RIBOSWITCH ; DISCOVERY ; IDENTIFICATION ; DIVERSITY ; RECOGNITION ; DEFICIENCY ; AFFINITY ; APTAMER |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/203280 |
专题 | 资源环境科学 |
作者单位 | 1.NCI, Chem Biol Lab, Frederick, MD 21701 USA; 2.NHLBI, Biochem & Biophys Ctr, Bldg 10, Bethesda, MD 20892 USA; 3.Natl Inst Adv Ind Sci & Technol, Biomed Res Inst, Tsukuba, Ibaraki 3058566, Japan |
推荐引用方式 GB/T 7714 | Connelly, Colleen M.,39;Amare, Adrian R.. Synthetic ligands for PreQ(1) riboswitches provide structural and mechanistic insights into targeting RNA tertiary structure[J]. NATURE COMMUNICATIONS,2019,10. |
APA | Connelly, Colleen M.,&39;Amare, Adrian R..(2019).Synthetic ligands for PreQ(1) riboswitches provide structural and mechanistic insights into targeting RNA tertiary structure.NATURE COMMUNICATIONS,10. |
MLA | Connelly, Colleen M.,et al."Synthetic ligands for PreQ(1) riboswitches provide structural and mechanistic insights into targeting RNA tertiary structure".NATURE COMMUNICATIONS 10(2019). |
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