Abstract
Multidrug efflux transporters recognize a variety of structurally unrelated compounds for which the molecular basis is poorly understood. For the resistance nodulation and cell division (RND) inner membrane component AcrB of the AcrAB-TolC multidrug efflux system from Escherichia coli, drug binding occurs at the access and deep binding pockets. These two binding areas are separated by an 11-amino-acid-residue-containing switch loop whose conformational flexibility is speculated to be essential for drug binding and transport. A G616N substitution in the switch loop has a distinct and local effect on the orientation of the loop and on the ability to transport larger drugs. Here, we report a distinct phenotypical pattern of drug recognition and transport for the G616N variant, indicating that drug substrates with minimal projection areas of >70 Å(2) are less well transported than other substrates.
Copyright © 2014, American Society for Microbiology. All Rights Reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Substitution*
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Anti-Bacterial Agents / chemistry*
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Anti-Bacterial Agents / pharmacology
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Binding Sites
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Biological Transport
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Crystallography, X-Ray
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Doxorubicin / chemistry
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Doxorubicin / pharmacology
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Drug Resistance, Multiple, Bacterial / genetics
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Escherichia coli / chemistry*
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Escherichia coli / drug effects
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Escherichia coli / genetics
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Escherichia coli / metabolism
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Escherichia coli Proteins / chemistry*
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Escherichia coli Proteins / genetics
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Escherichia coli Proteins / metabolism
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Gene Expression
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Humans
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Microbial Sensitivity Tests
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Minocycline / chemistry
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Minocycline / pharmacology
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Molecular Docking Simulation
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Molecular Weight
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Multidrug Resistance-Associated Proteins / chemistry*
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Multidrug Resistance-Associated Proteins / genetics
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Multidrug Resistance-Associated Proteins / metabolism
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Protein Binding
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Protein Structure, Secondary
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Protein Structure, Tertiary
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Xenobiotics / chemistry*
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Xenobiotics / pharmacology
Substances
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AcrB protein, E coli
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Anti-Bacterial Agents
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Escherichia coli Proteins
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Multidrug Resistance-Associated Proteins
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Xenobiotics
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Doxorubicin
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Minocycline