scholarly journals Overlapping Substrate Specificities in the Small Multidrug Resistance (SMR) Family of Transporters

2020 ◽  
Vol 118 (3) ◽  
pp. 130a
Author(s):  
Christian B. Macdonald ◽  
Ali A. Kermani ◽  
Randy B. Stockbridge
Keyword(s):  
Multidrug Resistance ◽  
Substrate Specificities ◽  
Small Multidrug Resistance

scholarly journals Overexpression of the Escherichia coli sugE Gene Confers Resistance to a Narrow Range of Quaternary Ammonium Compounds

2002 ◽  
Vol 184 (9) ◽  
pp. 2543-2545 ◽  
Author(s):  
Yong Joon Chung ◽  
Milton H. Saier
Keyword(s):  
Escherichia Coli ◽  
Drug Resistance ◽  
Multidrug Resistance ◽  
Quaternary Ammonium ◽  
Narrow Range ◽  
Quaternary Ammonium Compounds ◽  
High Level Expression ◽  
Small Multidrug Resistance ◽  
High Level ◽  
Ammonium Compounds

ABSTRACT SugE of Escherichia coli, first identified as a suppressor of groEL mutations but a member of the small multidrug resistance family, has not previously been shown to confer a drug resistance phenotype. We show that high-level expression of sugE leads to resistance to a subset of toxic quaternary ammonium compounds.

scholarly journals Putative paired small multidrug resistance family proteinsPsmrAB, the homolog of YvdSR, actually function as a novel two-component Na+/H+antiporter

2012 ◽  
Vol 338 (1) ◽  
pp. 31-38 ◽  
Author(s):  
Juquan Jiang ◽  
Lei Wang ◽  
Hua Zhang ◽  
Haiping Wu ◽  
Haipeng Huang ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Small Multidrug Resistance ◽  
Two Component

scholarly journals A kinetically-driven free exchange mechanism of EmrE antiport sacrifices coupling efficiency in favor of promiscuity

2017 ◽  
Author(s):  
Anne E. Robinson ◽  
Nathan E. Thomas ◽  
Emma A. Morrison ◽  
Bryan Balthazor ◽  
Katherine A. Henzler-Wildman
Keyword(s):  
Multidrug Resistance ◽  
Coupling Efficiency ◽  
Binding Pocket ◽  
Exchange Model ◽  
Drug Uptake ◽  
Drug Efflux ◽  
E Coli ◽  
Small Multidrug Resistance ◽  
Pure Exchange ◽  
Multidrug Resistance Transporter

ABSTRACTEmrE is a small multidrug resistance transporter found in E. coli that confers resistance to toxic polyaromatic cations due to its proton-coupled antiport of these substrates. Here we show that EmrE breaks the rules generally deemed essential for coupled antiport. NMR spectra reveal that EmrE can simultaneously bind and cotransport proton and drug. The functional consequence of this finding is an exceptionally promiscuous transporter: Not only can EmrE export diverse drug substrates, it can couple antiport of a drug to either one or two protons, performing both electrogenic and electroneutral transport of a single substrate. We present a new kinetically-driven free exchange model for EmrE antiport that is consistent with these results and recapitulates ΔpH-driven concentrative drug uptake. Our results suggest that EmrE sacrifices coupling efficiency for initial transport speed and multidrug specificity.SIGNIFICANCEEmrE facilitates E. coli multidrug resistance by coupling drug efflux to proton import. This antiport mechanism has been thought to occur via a pure exchange model which achieves coupled antiport by restricting when the single binding pocket can alternate access between opposite sides of the membrane. We test this model using NMR titrations and transport assays and find it cannot account for EmrE antiport activity. We propose a new kinetically-driven free exchange model of antiport with fewer restrictions that better accounts for the highly promiscuous nature of EmrE drug efflux. This model expands our understanding of coupled antiport and has implications for transporter design and drug development.

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