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Related Concept Videos

Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters01:16

Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters

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The pharmacogenetics of drug transporters is increasingly recognized as a critical factor influencing interindividual variability in drug absorption, distribution, and elimination. These membrane-bound proteins regulate drugs' movement across cellular barriers by actively pumping them out (efflux) or facilitating their uptake (influx). Among the major transporter families, ATP-binding cassette (ABC) and solute carrier (SLC) transporters play particularly prominent roles. Genetic polymorphisms...
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The Significance of Membrane Transport01:44

The Significance of Membrane Transport

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The transport of solutes across the cell membrane is essential for metabolic processes, like maintaining cell size and volume, generating the action potential, exchanging nutrients and gases, etc. Membrane transport can be either passive or active. It can be simple diffusion, facilitated, or mediated transport aided by transport proteins such as transporters and channels.
Transporters facilitate either an active or passive movement of solutes. They can allow a single-molecule transport down its...
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Carrier-Mediated Transport01:06

Carrier-Mediated Transport

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Carrier-mediated transport is a pivotal process in drug absorption, particularly for lipid-insoluble drugs, and encompasses facilitated diffusion and active transport. Facilitated diffusion allows drugs to move along their concentration gradient without energy expenditure, while active transport utilizes ATP to drive drug movement against this gradient.
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
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ABC Transporters: Exporter01:31

ABC Transporters: Exporter

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ATP-binding cassette or ABC transporter is the largest superfamily of integral membrane proteins. The transporters have transmembrane-binding domains (TMDs) and nucleotide-binding domains (NBDs). The TMDs are specific to their substrates, whereas the NBDs are similar to engines that complete ATP hydrolysis to complete the substrate transport. They can be full transporters consisting of two TMDs and NBDs, half transporters with one TMD and NBD, while some encoded with a single TMD or NBD are...
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Membrane Transporters01:31

Membrane Transporters

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Transporters are essential membrane transport proteins with functions related to cell nutrition, homeostasis, communication, etc. Approximately 7% of all genes in the human genome code for transporters or transporter-related proteins.
Transporters are mainly composed of alpha-helices, built from bundles of ten or more helices traversing the plasma membrane. The solute-binding sites are located midway, where some of the helices are broken or distorted, making space for the binding site through...
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Secondary Active Transport01:32

Secondary Active Transport

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One example of how cells use the energy contained in electrochemical gradients is demonstrated by glucose transport into cells. The ion vital to this process is sodium (Na+), which is typically present in higher concentrations extracellularly than in the cytosol. Such a concentration difference is due, in part, to the action of an enzyme "pump" embedded in the cellular membrane that actively expels Na+ from a cell. Importantly, as this pump contributes to the high concentration of...
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Related Experiment Video

Updated: Apr 19, 2026

Expression, Detergent Solubilization, and Purification of a Membrane Transporter, the MexB Multidrug Resistance Protein
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Expression, Detergent Solubilization, and Purification of a Membrane Transporter, the MexB Multidrug Resistance Protein

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Specificity determinants in small multidrug transporters.

Shlomo Brill1, Ofir Sade-Falk1, Yael Elbaz-Alon1

  • 1Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, 91904 Jerusalem, Israel.

Journal of Molecular Biology
|December 6, 2014
PubMed
Summary

Understanding multidrug transporters (MDTs) is key to combating antibiotic resistance. A specific residue in EmrE was identified as crucial for methyl viologen transport and resistance, offering insights into transporter specificity.

Keywords:
EmrEantibiotic resistanceion-coupled antiportersmethyl viologenmultidrug transporters

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Characterization of Membrane Transporters by Heterologous Expression in E. coli and Production of Membrane Vesicles
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Expression, Detergent Solubilization, and Purification of a Membrane Transporter, the MexB Multidrug Resistance Protein
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Characterization of Membrane Transporters by Heterologous Expression in E. coli and Production of Membrane Vesicles
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Characterization of Membrane Transporters by Heterologous Expression in E. coli and Production of Membrane Vesicles

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Area of Science:

  • Microbiology
  • Molecular Biology
  • Biochemistry

Background:

  • Multiple-antibiotic resistance is a significant global health threat.
  • Multidrug transporters (MDTs) contribute to resistance by actively removing antibiotics from pathogen cells.
  • MDTs exhibit polyspecificity, conferring resistance to multiple drugs via a single transporter.

Purpose of the Study:

  • To elucidate the molecular mechanism of substrate recognition in the EmrE multidrug transporter from Escherichia coli.
  • To identify key molecular determinants responsible for methyl viologen (MV(2+)) transport and resistance mediated by EmrE.

Main Methods:

  • Employed a combined bioinformatic and biochemical approach.
  • Investigated the role of specific amino acid residues in substrate binding and transport.
  • Utilized homologous SMR transporters from Bacillus pertussis and Mycobacterium tuberculosis for comparative analysis.

Main Results:

  • Identified a specific Ala to Ser residue replacement in SMRs that confers robust MV(2+) resistance and transport.
  • Demonstrated that this residue is uniquely positioned in the binding site, mediating MV(2+) specificity.
  • Observed negligible effects on the interaction with other substrates, highlighting selective specificity.

Conclusions:

  • The identified residue is a critical determinant for MV(2+) transport and resistance in EmrE and homologous transporters.
  • This finding provides insights into achieving specificity within polyspecific transporter binding pockets.
  • Potential for manipulating these transporters to bind designed drugs, offering new therapeutic strategies.