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-Structure paper
タイトル | cryoEM-Guided Development of Antibiotics for Drug-Resistant Bacteria. |
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ジャーナル・号・ページ | ChemMedChem, Vol. 14, Issue 5, Page 527-531, Year 2019 |
掲載日 | 2019年3月5日 |
著者 | Matthew J Belousoff / Hari Venugopal / Alexander Wright / Samuel Seoner / Isabella Stuart / Chris Stubenrauch / Rebecca S Bamert / David W Lupton / Trevor Lithgow / |
PubMed 要旨 | While the ribosome is a common target for antibiotics, challenges with crystallography can impede the development of new bioactives using structure-based drug design approaches. In this study we ...While the ribosome is a common target for antibiotics, challenges with crystallography can impede the development of new bioactives using structure-based drug design approaches. In this study we exploit common structural features present in linezolid-resistant forms of both methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) to redesign the antibiotic. Enabled by rapid and facile cryoEM structures, this process has identified (S)-2,2-dichloro-N-((3-(3-fluoro-4-morpholinophenyl)-2-oxooxazolidin-5-yl)methyl)acetamide (LZD-5) and (S)-2-chloro-N-((3-(3-fluoro-4-morpholinophenyl)-2-oxooxazolidin-5-yl)methyl) acetamide (LZD-6), which inhibit the ribosomal function and growth of linezolid-resistant MRSA and VRE. The strategy discussed highlights the potential for cryoEM to facilitate the development of novel bioactive materials. |
リンク | ChemMedChem / PubMed:30667174 |
手法 | EM (単粒子) |
解像度 | 3.1 Å |
構造データ | |
化合物 | ChemComp-G6V: ChemComp-G6M: |
由来 |
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キーワード | Ribosome/Antibiotic / antibiotic complex / linezolid / oxazolidinone / 50S / ribosome / Ribosome-Antibiotic complex |