A model of a transmembrane drug-efflux pump from Gram-negative bacteria

被引：65

作者：

Fernandez-Recio, J ^{[1
]}

Walas, F ^{[1
]}

Federici, L ^{[1
]}

Pratap, JV ^{[1
]}

Bavro, VN ^{[1
]}

Miguel, RN ^{[1
]}

Mizuguchi, K ^{[1
]}

Luisi, B ^{[1
]}

机构：

[1] Univ Cambridge, Dept Biochem, Cambridge CB2 1GA, England

来源：

FEBS LETTERS | 2004年 / 578卷 / 1-2期

基金：

英国惠康基金;

关键词：

pump-channel; multidrug resistance; transmembrane transport; homology modelling; molecular docking and allostery;

D O I：

10.1016/j.febslet.2004.10.097

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：5 / 9

页数：5

共 35 条

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