7P7T

PoxtA-EQ2 antibiotic resistance ABCF bound to E. faecalis 70S ribosome, state III

これはPDB形式変換不可エントリーです。

7P7T の概要

• エントリーDOI: 10.2210/pdb7p7t/pdb
• EMDBエントリー: 13244
• 分子名称: ARE-ABC-F family resistance factor PoxtA, 23S rRNA, 5S rRNA, ... (61 entities in total)
• 機能のキーワード: ribosome, enterococcus faecalis, poxta, abcf, antibiotic resistance protein
• 由来する生物種: Enterococcus faecalis; 詳細
• タンパク質・核酸の鎖数: 54
• 化学式量合計: 2267704.31

構造登録者

Crowe-McAuliffe, C.,Wilson, D.N. (登録日: 2021-07-20, 公開日: 2022-02-23, 最終更新日: 2024-07-17)

主引用文献

Crowe-McAuliffe, C.,Murina, V.,Turnbull, K.J.,Huch, S.,Kasari, M.,Takada, H.,Nersisyan, L.,Sundsfjord, A.,Hegstad, K.,Atkinson, G.C.,Pelechano, V.,Wilson, D.N.,Hauryliuk, V.
Structural basis for PoxtA-mediated resistance to phenicol and oxazolidinone antibiotics.
Nat Commun, 13:1860-1860, 2022

PubMed Abstract: 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.

PubMed: 35387982
DOI: 10.1038/s41467-022-29274-9

実験手法

ELECTRON MICROSCOPY (2.9 Å)