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Structures of Gate Loop Variants of the AcrB Drug Efflux Pump Bound by Erythromycin Substrate.

Published version
Peer-reviewed

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Authors

Ababou, Abdessamad 
Koronakis, Vassilis  ORCID logo  https://orcid.org/0000-0002-1353-1092

Abstract

Gram-negative bacteria such as E. coli use tripartite efflux pumps such as AcrAB-TolC to expel antibiotics and noxious compounds. A key feature of the inner membrane transporter component, AcrB, is a short stretch of residues known as the gate/switch loop that divides the proximal and distal substrate binding pockets. Amino acid substitutions of the gate loop are known to decrease antibiotic resistance conferred by AcrB. Here we present two new AcrB gate loop variants, the first stripped of its bulky side chains, and a second in which the gate loop is removed entirely. By determining the crystal structures of the variant AcrB proteins in the presence and absence of erythromycin and assessing their ability to confer erythromycin tolerance, we demonstrate that the gate loop is important for AcrB export activity but is not required for erythromycin binding.

Description

Keywords

Biological Transport, Erythromycin, Escherichia coli, Escherichia coli Proteins, Models, Molecular, Multidrug Resistance-Associated Proteins, Mutation, Protein Binding, Protein Domains

Journal Title

PLoS One

Conference Name

Journal ISSN

1932-6203
1932-6203

Volume Title

11

Publisher

Public Library of Science (PLoS)
Sponsorship
Medical Research Council (MR/N000994/1)
Medical Research Council (G1001104)
Medical Research Council; Wellcome Trust