6Z12

Salmonella AcrB solubilised in the SMA copolymer

6Z12 の概要

• エントリーDOI: 10.2210/pdb6z12/pdb
• EMDBエントリー: 4460
• 分子名称: Efflux pump membrane transporter (1 entity in total)
• 機能のキーワード: acrb, membrane protein
• 由来する生物種: Salmonella enterica I
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 341277.68

構造登録者

Muench, s.p.,Johnson, R.M. (登録日: 2020-05-11, 公開日: 2020-07-22, 最終更新日: 2024-05-15)

主引用文献

Johnson, R.M.,Fais, C.,Parmar, M.,Cheruvara, H.,Marshall, R.L.,Hesketh, S.J.,Feasey, M.C.,Ruggerone, P.,Vargiu, A.V.,Postis, V.L.G.,Muench, S.P.,Bavro, V.N.
Cryo-EM Structure and Molecular Dynamics Analysis of the Fluoroquinolone Resistant Mutant of the AcrB Transporter fromSalmonella.
Microorganisms, 8:-, 2020

PubMed Abstract: is an important genus of Gram-negative pathogens, treatment of which has become problematic due to increases in antimicrobial resistance. This is partly attributable to the overexpression of tripartite efflux pumps, particularly the constitutively expressed AcrAB-TolC. Despite its clinical importance, the structure of the AcrB transporter remained unknown to-date, with much of our structural understanding coming from the orthologue. Here, by taking advantage of the styrene maleic acid (SMA) technology to isolate membrane proteins with closely associated lipids, we report the very first experimental structure of AcrB transporter. Furthermore, this novel structure provides additional insight into mechanisms of drug efflux as it bears the mutation (G288D), originating from a clinical isolate of Typhimurium presenting an increased resistance to fluoroquinolones. Experimental data are complemented by state-of-the-art molecular dynamics (MD) simulations on both the wild type and G288D variant of AcrB. Together, these reveal several important differences with respect to the protein, providing insights into the role of the G288D mutation in increasing drug efflux and extending our understanding of the mechanisms underlying antibiotic resistance.

PubMed: 32585951
DOI: 10.3390/microorganisms8060943

実験手法

ELECTRON MICROSCOPY (4.6 Å)