6Q4O

Fusidic acid bound AcrB_I27A

6Q4O の概要

• エントリーDOI: 10.2210/pdb6q4o/pdb
• 分子名称: Multidrug efflux pump subunit AcrB, DODECANE, (2S)-3-hydroxypropane-1,2-diyl didecanoate, ... (14 entities in total)
• 機能のキーワード: multidrug efflux protein, membrane protein, transport protein
• 由来する生物種: Escherichia coli K-12; 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 394629.47

構造登録者

Tam, H.K.,Pos, K.M. (登録日: 2018-12-06, 公開日: 2019-11-13, 最終更新日: 2024-01-24)

主引用文献

Tam, H.K.,Malviya, V.N.,Foong, W.E.,Herrmann, A.,Malloci, G.,Ruggerone, P.,Vargiu, A.V.,Pos, K.M.
Binding and Transport of Carboxylated Drugs by the Multidrug Transporter AcrB.
J.Mol.Biol., 432:861-877, 2020

PubMed Abstract: AcrAB(Z)-TolC is the main drug efflux transporter complex in Escherichia coli. The extrusion of various toxic compounds depends on several drug binding sites within the trimeric AcrB transporter. Membrane-localized carboxylated substrates, such as fusidic acid and hydrophobic β-lactams, access the pump via a groove between the transmembrane helices TM1 and TM2. In this article, the transport route from the initial TM1/TM2 groove binding site toward the deep binding pocket located in the periplasmic part has been addressed via molecular modeling studies followed by functional and structural characterization of several AcrB variants. We propose that membrane-embedded drugs bind initially to the TM1/TM2 groove, are oriented by the AcrB PN2 subdomain, and are subsequently transported via a PN2/PC1 interface pathway directly toward the deep binding pocket. Our work emphasizes the exploitation of multiple transport pathways by AcrB tuned to substrate physicochemical properties related to the polyspecificity of the pump.

PubMed: 31881208
DOI: 10.1016/j.jmb.2019.12.025

実験手法

X-RAY DIFFRACTION (2.8 Å)