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首页> 外文期刊>Journal of Molecular Biology >Binding and Transport of Carboxylated Drugs by the Multidrug Transporter AcrB
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Binding and Transport of Carboxylated Drugs by the Multidrug Transporter AcrB

机译：羧化药物的结合和转运通过多药传输仪ACRB

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摘要

AcrAB(Z)-ToIC 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 beta-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. (C) 2020 Elsevier Ltd. All rights reserved.
机译：ACRAB（Z）-TOIC是大肠杆菌的主要药物流出转运综合体。各种毒性化合物的挤出取决于三聚体ACRB转运物内的几个药物结合位点。膜局部化的羧化底物，例如浑浊酸和疏水性β-内酰胺，通过跨膜螺旋TM1和TM2之间的凹槽进入泵。在本文中，通过分子建模研究，从初始TM1 / TM2沟槽结合位点朝向位于周质部件的深层结合口袋的运输路径已经通过分子建模研究，然后进行了几种用于多种ACRB变体的功能性和结构表征。我们提出膜嵌入的药物最初与TM1 / TM2槽结合，由ACRB PN2子域定向，随后通过PN2 / PC1接口路径直接向深色装订口袋传送。我们的作品强调了通过CRAB调整到与泵的多特异性相关的基底物理化学性质的多种运输途径的开发。 （c）2020 elestvier有限公司保留所有权利。

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