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-Structure paper
タイトル | Sal-type ABC-F proteins: intrinsic and common mediators of pleuromutilin resistance by target protection in staphylococci. |
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ジャーナル・号・ページ | Nucleic Acids Res, Vol. 50, Issue 4, Page 2128-2142, Year 2022 |
掲載日 | 2022年2月28日 |
著者 | Merianne Mohamad / David Nicholson / Chayan Kumar Saha / Vasili Hauryliuk / Thomas A Edwards / Gemma C Atkinson / Neil A Ranson / Alex J O'Neill / |
PubMed 要旨 | The first member of the pleuromutilin (PLM) class suitable for systemic antibacterial chemotherapy in humans recently entered clinical use, underscoring the need to better understand mechanisms of ...The first member of the pleuromutilin (PLM) class suitable for systemic antibacterial chemotherapy in humans recently entered clinical use, underscoring the need to better understand mechanisms of PLM resistance in disease-causing bacterial genera. Of the proteins reported to mediate PLM resistance in staphylococci, the least-well studied to date is Sal(A), a putative ABC-F NTPase that-by analogy to other proteins of this type-may act to protect the ribosome from PLMs. Here, we establish the importance of Sal proteins as a common source of PLM resistance across multiple species of staphylococci. Sal(A) is revealed as but one member of a larger group of Sal-type ABC-F proteins that vary considerably in their ability to mediate resistance to PLMs and other antibiotics. We find that specific sal genes are intrinsic to particular staphylococcal species, and show that this gene family is likely ancestral to the genus Staphylococcus. Finally, we solve the cryo-EM structure of a representative Sal-type protein (Sal(B)) in complex with the staphylococcal 70S ribosome, revealing that Sal-type proteins bind into the E site to mediate target protection, likely by displacing PLMs and other antibiotics via an allosteric mechanism. |
リンク | Nucleic Acids Res / PubMed:35137182 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.9 Å |
構造データ | EMDB-13191, PDB-7p48: |
化合物 | ChemComp-ZN: ChemComp-ATP: ChemComp-MG: |
由来 |
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キーワード | RIBOSOMAL PROTEIN / antibiotic resistance (抗微生物薬耐性) / ABC-F protein / ribosome (リボソーム) |