7M4Z

A. baumannii Ribosome-Eravacycline complex: hpf-bound 70S

これはPDB形式変換不可エントリーです。

7M4Z の概要

• エントリーDOI: 10.2210/pdb7m4z/pdb
• EMDBエントリー: 23671
• 分子名称: 50S ribosomal protein L33, 50S ribosomal protein L5, 50S ribosomal protein L6, ... (56 entities in total)
• 機能のキーワード: acinetobacter baumannii, ribosome, eravacycline, antibiotic
• 由来する生物種: Acinetobacter baumannii AB0057; 詳細
• タンパク質・核酸の鎖数: 52
• 化学式量合計: 2154157.03

構造登録者

Morgan, C.E.,Yu, E.W. (登録日: 2021-03-22, 公開日: 2021-05-19, 最終更新日: 2025-03-19)

主引用文献

Zhang, Z.,Morgan, C.E.,Bonomo, R.A.,Yu, E.W.
Cryo-EM Determination of Eravacycline-Bound Structures of the Ribosome and the Multidrug Efflux Pump AdeJ of Acinetobacter baumannii.
Mbio, 12:e0103121-e0103121, 2021

PubMed Abstract: Antibiotic-resistant strains of the Gram-negative pathogen Acinetobacter baumannii have emerged as a significant global health threat. One successful therapeutic option to treat bacterial infections has been to target the bacterial ribosome. However, in many cases, multidrug efflux pumps within the bacterium recognize and extrude these clinically important antibiotics designed to inhibit the protein synthesis function of the bacterial ribosome. Thus, multidrug efflux within A. baumannii and other highly drug-resistant strains is a major cause of failure of drug-based treatments of infectious diseases. We here report the first structures of the cinetobacter rug fflux (Ade)J pump in the presence of the antibiotic eravacycline, using single-particle cryo-electron microscopy (cryo-EM). We also describe cryo-EM structures of the eravacycline-bound forms of the A. baumannii ribosome, including the 70S, 50S, and 30S forms. Our data indicate that the AdeJ pump primarily uses hydrophobic interactions to bind eravacycline, while the 70S ribosome utilizes electrostatic interactions to bind this drug. Our work here highlights how an antibiotic can bind multiple bacterial targets through different mechanisms and potentially enables drug optimization by taking advantage of these different modes of ligand binding. Acinetobacter baumannii has developed into a highly antibiotic-resistant Gram-negative pathogen. The prevalent AdeJ multidrug efflux pump mediates resistance to different classes of antibiotics known to inhibit the function of the 70S ribosome. Here, we report the first structures of the A. baumannii AdeJ pump, both in the absence and presence of eravacycline. We also describe structures of the A. baumannii ribosome bound by this antibiotic. Our results indicate that AdeJ and the ribosome use very distinct binding modes for drug recognition. Our work will ultimately enable structure-based drug discovery to combat antibiotic-resistant A. baumannii infection.

PubMed: 34044590
DOI: 10.1128/mBio.01031-21

実験手法

ELECTRON MICROSCOPY (2.92 Å)