Structure and mechanism of drug efflux machinery in Gram negative bacteria.

In Gram-negative bacteria, multi-component machines that span the inner and outer membranes actively extrude drugs and other toxic small compounds. Many of these machines are assembled principally from three different types of components: i) an outer membrane protein that acts as a channel and opens...

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Main Authors: Pietras, Z, Bavro, V, Furnham, N, Pellegrini-Calace, M, Milner-White, E, Luisi, B
Format: Journal article
Language:English
Published: 2008
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author Pietras, Z
Bavro, V
Furnham, N
Pellegrini-Calace, M
Milner-White, E
Luisi, B
author_facet Pietras, Z
Bavro, V
Furnham, N
Pellegrini-Calace, M
Milner-White, E
Luisi, B
author_sort Pietras, Z
collection OXFORD
description In Gram-negative bacteria, multi-component machines that span the inner and outer membranes actively extrude drugs and other toxic small compounds. Many of these machines are assembled principally from three different types of components: i) an outer membrane protein that acts as a channel and opens from a sealed resting state during the transport process, ii) an inner membrane protein that transduces proton electrochemical energy into vectorial displacement of the transported compounds, and iii) a bridging, periplasmic component that links the inner and outer membrane proteins. The pumps may assemble transiently, and the association of components is favoured by engaged substrate and the trans-membrane electrochemical potential. We describe recent structural and functional studies on the individual pump components and discuss models that explain how they associate in the dynamic, active assembly. Based on the available data, we suggest that the assembly of these multi-drug efflux pumps is accompanied by induced fit of the outer membrane component driven mainly by accommodation of the periplasmic component.
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spelling oxford-uuid:b851d3db-df0b-41b4-b0a4-b36801aec4212022-03-27T04:54:58ZStructure and mechanism of drug efflux machinery in Gram negative bacteria.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b851d3db-df0b-41b4-b0a4-b36801aec421EnglishSymplectic Elements at Oxford2008Pietras, ZBavro, VFurnham, NPellegrini-Calace, MMilner-White, ELuisi, BIn Gram-negative bacteria, multi-component machines that span the inner and outer membranes actively extrude drugs and other toxic small compounds. Many of these machines are assembled principally from three different types of components: i) an outer membrane protein that acts as a channel and opens from a sealed resting state during the transport process, ii) an inner membrane protein that transduces proton electrochemical energy into vectorial displacement of the transported compounds, and iii) a bridging, periplasmic component that links the inner and outer membrane proteins. The pumps may assemble transiently, and the association of components is favoured by engaged substrate and the trans-membrane electrochemical potential. We describe recent structural and functional studies on the individual pump components and discuss models that explain how they associate in the dynamic, active assembly. Based on the available data, we suggest that the assembly of these multi-drug efflux pumps is accompanied by induced fit of the outer membrane component driven mainly by accommodation of the periplasmic component.
spellingShingle Pietras, Z
Bavro, V
Furnham, N
Pellegrini-Calace, M
Milner-White, E
Luisi, B
Structure and mechanism of drug efflux machinery in Gram negative bacteria.
title Structure and mechanism of drug efflux machinery in Gram negative bacteria.
title_full Structure and mechanism of drug efflux machinery in Gram negative bacteria.
title_fullStr Structure and mechanism of drug efflux machinery in Gram negative bacteria.
title_full_unstemmed Structure and mechanism of drug efflux machinery in Gram negative bacteria.
title_short Structure and mechanism of drug efflux machinery in Gram negative bacteria.
title_sort structure and mechanism of drug efflux machinery in gram negative bacteria
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