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Computational Study of Correlated Domain Motions in the AcrB Efflux Transporter

As active part of the major efflux system in E. coli bacteria, AcrB is responsible for the uptake and pumping of toxic substrates from the periplasm toward the extracellular space. In combination with the channel protein TolC and membrane fusion protein AcrA, this efflux pump is able to help the bac...

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Autores principales: Schulz, Robert, Vargiu, Attilio V., Ruggerone, Paolo, Kleinekathöfer, Ulrich
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4313061/
https://www.ncbi.nlm.nih.gov/pubmed/25685792
http://dx.doi.org/10.1155/2015/487298
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author Schulz, Robert
Vargiu, Attilio V.
Ruggerone, Paolo
Kleinekathöfer, Ulrich
author_facet Schulz, Robert
Vargiu, Attilio V.
Ruggerone, Paolo
Kleinekathöfer, Ulrich
author_sort Schulz, Robert
collection PubMed
description As active part of the major efflux system in E. coli bacteria, AcrB is responsible for the uptake and pumping of toxic substrates from the periplasm toward the extracellular space. In combination with the channel protein TolC and membrane fusion protein AcrA, this efflux pump is able to help the bacterium to survive different kinds of noxious compounds. With the present study we intend to enhance the understanding of the interactions between the domains and monomers, for example, the transduction of mechanical energy from the transmembrane domain into the porter domain, correlated motions of different subdomains within monomers, and cooperative effects between monomers. To this end, targeted molecular dynamics simulations have been employed either steering the whole protein complex or specific parts thereof. By forcing only parts of the complex towards specific conformational states, the risk for transient artificial conformations during the simulations is reduced. Distinct cooperative effects between the monomers in AcrB have been observed. Possible allosteric couplings have been identified providing microscopic insights that might be exploited to design more efficient inhibitors of efflux systems.
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spelling pubmed-43130612015-02-15 Computational Study of Correlated Domain Motions in the AcrB Efflux Transporter Schulz, Robert Vargiu, Attilio V. Ruggerone, Paolo Kleinekathöfer, Ulrich Biomed Res Int Research Article As active part of the major efflux system in E. coli bacteria, AcrB is responsible for the uptake and pumping of toxic substrates from the periplasm toward the extracellular space. In combination with the channel protein TolC and membrane fusion protein AcrA, this efflux pump is able to help the bacterium to survive different kinds of noxious compounds. With the present study we intend to enhance the understanding of the interactions between the domains and monomers, for example, the transduction of mechanical energy from the transmembrane domain into the porter domain, correlated motions of different subdomains within monomers, and cooperative effects between monomers. To this end, targeted molecular dynamics simulations have been employed either steering the whole protein complex or specific parts thereof. By forcing only parts of the complex towards specific conformational states, the risk for transient artificial conformations during the simulations is reduced. Distinct cooperative effects between the monomers in AcrB have been observed. Possible allosteric couplings have been identified providing microscopic insights that might be exploited to design more efficient inhibitors of efflux systems. Hindawi Publishing Corporation 2015 2015-01-05 /pmc/articles/PMC4313061/ /pubmed/25685792 http://dx.doi.org/10.1155/2015/487298 Text en Copyright © 2015 Robert Schulz et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Schulz, Robert
Vargiu, Attilio V.
Ruggerone, Paolo
Kleinekathöfer, Ulrich
Computational Study of Correlated Domain Motions in the AcrB Efflux Transporter
title Computational Study of Correlated Domain Motions in the AcrB Efflux Transporter
title_full Computational Study of Correlated Domain Motions in the AcrB Efflux Transporter
title_fullStr Computational Study of Correlated Domain Motions in the AcrB Efflux Transporter
title_full_unstemmed Computational Study of Correlated Domain Motions in the AcrB Efflux Transporter
title_short Computational Study of Correlated Domain Motions in the AcrB Efflux Transporter
title_sort computational study of correlated domain motions in the acrb efflux transporter
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4313061/
https://www.ncbi.nlm.nih.gov/pubmed/25685792
http://dx.doi.org/10.1155/2015/487298
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