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-Structure paper
タイトル | Structural basis for PoxtA-mediated resistance to phenicol and oxazolidinone antibiotics. |
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ジャーナル・号・ページ | Nat Commun, Vol. 13, Issue 1, Page 1860, Year 2022 |
掲載日 | 2022年4月6日 |
著者 | Caillan Crowe-McAuliffe / Victoriia Murina / Kathryn Jane Turnbull / Susanne Huch / Marje Kasari / Hiraku Takada / Lilit Nersisyan / Arnfinn Sundsfjord / Kristin Hegstad / Gemma C Atkinson / Vicent Pelechano / Daniel N Wilson / Vasili Hauryliuk / |
PubMed 要旨 | PoxtA and OptrA are ATP binding cassette (ABC) proteins of the F subtype (ABCF). They confer resistance to oxazolidinone and phenicol antibiotics, such as linezolid and chloramphenicol, which stall ...PoxtA and OptrA are ATP binding cassette (ABC) proteins of the F subtype (ABCF). They confer resistance to oxazolidinone and phenicol antibiotics, such as linezolid and chloramphenicol, which stall translating ribosomes when certain amino acids are present at a defined position in the nascent polypeptide chain. These proteins are often encoded on mobile genetic elements, facilitating their rapid spread amongst Gram-positive bacteria, and are thought to confer resistance by binding to the ribosome and dislodging the bound antibiotic. However, the mechanistic basis of this resistance remains unclear. Here we refine the PoxtA spectrum of action, demonstrate alleviation of linezolid-induced context-dependent translational stalling, and present cryo-electron microscopy structures of PoxtA in complex with the Enterococcus faecalis 70S ribosome. PoxtA perturbs the CCA-end of the P-site tRNA, causing it to shift by ∼4 Å out of the ribosome, corresponding to a register shift of approximately one amino acid for an attached nascent polypeptide chain. We postulate that the perturbation of the P-site tRNA by PoxtA thereby alters the conformation of the attached nascent chain to disrupt the drug binding site. |
リンク | Nat Commun / PubMed:35387982 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.4 - 3.1 Å |
構造データ | EMDB-13241, PDB-7p7q: EMDB-13242, PDB-7p7r: EMDB-13243, PDB-7p7s: EMDB-13244, PDB-7p7t: EMDB-13245, PDB-7p7u: |
化合物 | ChemComp-ATP: ChemComp-MG: ChemComp-K: ChemComp-ZN: ChemComp-PUT: ChemComp-SCM: ChemComp-HOH: |
由来 |
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キーワード | RIBOSOME / Enterococcus faecalis / PoxtA / ABCF / antibiotic resistance protein / P-tRNA |