A model of a transmembrane drug-efflux pump from Gram-negative bacteria
A model of a transmembrane drug-efflux pump from Gram-negative bacteria
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DOI：
10.1016/j.febslet.2004.10.097
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发表时间：
2004-12-03
期刊：
影响因子：
3.5
通讯作者：
Luisi, B
中科院分区：
文献类型：
--
作者：
Fernandez-Recio, J;Walas, F;Luisi, B
在革兰氏阴性细菌中，耐药性部分归因于跨膜外排泵的活性，该泵由三种类型的蛋白质组成。大肠杆菌的代表性泵是三聚体外膜蛋白 TolC（一种变构通道）、三聚体内膜质子反向转运蛋白 AcrB 和周质蛋白 AcrA 的组装体。该泵利用质子电化学力从细菌中矢量地排出药物。可以获得来自大肠杆菌的 TolC 和 AcrB 以及来自铜绿假单胞菌的 AcrA 同源物 MexA 的晶体结构。基于同源建模和分子对接，我们展示了 AcrA、AcrB 和 TolC 如何组装形成三方泵，以及在运输过程中如何发生变构。 (C) 2004 年由 Elsevier B.V. 代表欧洲生化学会联合会出版。
In Gram-negative bacteria, drug resistance is due in part to the activity of transmembrane efflux-pumps, which are composed of three types of proteins. A representative pump from Escherichia coli is an assembly of the trimeric outer-membrane protein TolC, which is an allosteric channel, the trimeric inner-membrane proton-antiporter AcrB, and the periplasmic protein, AcrA. The pump displaces drugs vectorially from the bacterium using proton electrochemical force. Crystal structures are available for TolC and AcrB from E. coli, and for the AcrA homologue MexA from Pseudomonas aeruginosa. Based on homology modelling and molecular docking, we show how AcrA, AcrB and TolC might assemble to form a tripartite pump, and how allostery may occur during transport. (C) 2004 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.