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-Structure paper
| タイトル | Basis of narrow-spectrum activity of fidaxomicin on Clostridioides difficile. |
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| ジャーナル・号・ページ | Nature, Vol. 604, Issue 7906, Page 541-545, Year 2022 |
| 掲載日 | 2022年4月6日 |
著者 | Xinyun Cao / Hande Boyaci / James Chen / Yu Bao / Robert Landick / Elizabeth A Campbell / ![]() |
| PubMed 要旨 | Fidaxomicin (Fdx) is widely used to treat Clostridioides difficile (Cdiff) infections, but the molecular basis of its narrow-spectrum activity in the human gut microbiome remains unknown. Cdiff ...Fidaxomicin (Fdx) is widely used to treat Clostridioides difficile (Cdiff) infections, but the molecular basis of its narrow-spectrum activity in the human gut microbiome remains unknown. Cdiff infections are a leading cause of nosocomial deaths. Fidaxomicin, which inhibits RNA polymerase, targets Cdiff with minimal effects on gut commensals, reducing recurrence of Cdiff infection. Here we present the cryo-electron microscopy structure of Cdiff RNA polymerase in complex with fidaxomicin and identify a crucial fidaxomicin-binding determinant of Cdiff RNA polymerase that is absent in most gut microbiota such as Proteobacteria and Bacteroidetes. By combining structural, biochemical, genetic and bioinformatic analyses, we establish that a single residue in Cdiff RNA polymerase is a sensitizing element for fidaxomicin narrow-spectrum activity. Our results provide a blueprint for targeted drug design against an important human pathogen. |
リンク | Nature / PubMed:35388215 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 3.26 Å |
| 構造データ | EMDB-23210, PDB-7l7b: |
| 化合物 | ![]() ChemComp-ZN: ![]() ChemComp-MG: ![]() ChemComp-FI8: ![]() ChemComp-HOH: |
| 由来 |
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キーワード | TRANSCRIPTION/INHIBITOR / fidaxomicin / Clostridioides difficile RNA polymerase / TRANSCRIPTION / TRANSCRIPTION-INHIBITOR complex |
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clostridia bacterium (バクテリア)
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