Identification and analysis of novel small molecule inhibitors of RNase E: Implications for antibacterial targeting and regulation of RNase E
| Autor: | Helen S. Atkins, Louise E. Butt, Paul A. Cox, Bailei C. Spelman, Anastasia J. Callaghan, Charlotte E. Mardle, Darren M. Gowers, Layla R. Goddard, Helen A. Vincent |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
RNase P In silico Endoribonuclease Biophysics APC-PAID Antibacterial target medicine.disease_cause Biochemistry Bacterial cell structure lcsh:Biochemistry BB/J016179/1 03 medical and health sciences 0302 clinical medicine Metabolite-mediated regulation medicine lcsh:QD415-436 Virtual high-throughput screening (vHTS) lcsh:QH301-705.5 Escherichia coli Francisella tularensis biology Chemistry RCUK biology.organism_classification Small molecule 030104 developmental biology Endoribonuclease RNase E lcsh:Biology (General) BBSRC 030220 oncology & carcinogenesis Small molecule inhibitor Bacteria Research Article |
| Zdroj: | Biochemistry and Biophysics Reports Mardle, C E, Goddard, L, Spelman, B C, Atkins, H S, Butt, L, Cox, P, Gowers, D, Vincent, H & Callaghan, A 2020, ' Identification and analysis of novel small molecule inhibitors of RNase E: implications for antibacterial targeting and regulation of RNase E ', Biochemistry and Biophysics Reports, vol. 23, 100773 . https://doi.org/10.1016/j.bbrep.2020.100773 Biochemistry and Biophysics Reports, Vol 23, Iss, Pp 100773-(2020) |
| ISSN: | 2405-5808 |
| DOI: | 10.1016/j.bbrep.2020.100773 |
| Popis: | Increasing resistance of bacteria to antibiotics is a serious global challenge and there is a need to unlock the potential of novel antibacterial targets. One such target is the essential prokaryotic endoribonuclease RNase E. Using a combination of in silico high-throughput screening and in vitro validation we have identified three novel small molecule inhibitors of RNase E that are active against RNase E from Escherichia coli, Francisella tularensis and Acinetobacter baumannii. Two of the inhibitors are non-natural small molecules that could be suitable as lead compounds for the development of broad-spectrum antibiotics targeting RNase E. The third small molecule inhibitor is glucosamine-6-phosphate, a precursor of bacterial cell envelope peptidoglycans and lipopolysaccharides, hinting at a novel metabolite-mediated mechanism of regulation of RNase E. Highlights • RNase E, an essential bacterial endoribonuclease, is a potential antibacterial target. • Three novel small molecule inhibitors of RNase E are identified. • Each inhibitor is active against RNase E from E. coli, F. tularensis and A. baumannii. • Two, as non-natural compounds, are suitable lead compounds for antibiotic development. • One, a metabolite, is a potential novel regulator of RNase E. |
| Databáze: | OpenAIRE |
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