ArticleMolecular microbiology2010
Substrate path in the AcrB multidrug efflux pump of Escherichia coli.
Article in Molecular microbiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed.
- Labeling of Specific Residues of the Multidrug Transporter AcrB with Its Fluorescent Substrate.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Regulation, structure, and activity of theAntimicrobial agents and chemotherapy · 2025Review
- RND/HAE-1 members in the Pseudomonadota phylum: exploring multidrug resistance.Biophysical reviews · 2025Review
- Insights into substrate recognition and export tunnel preferences in the efflux transporter AcrB.Protein science : a publication of the Protein Society · 2025Article
- Specificity and tunability of efflux pumps: A new role for the proton gradient?PLoS computational biology · 2025Article
- Two-faced Janus SkQ1/SkQR1: patterns and molecular volume threshold for substrate recognition by the AcrAB-TolC pump.Frontiers in pharmacology · 2025Article
- AcrAB-TolC, a major efflux pump in Gram negative bacteria: toward understanding its operation mechanism.BMB reports · 2023Review
- Emergence of two AcrB substitutions conferring multidrug resistance toAntimicrobial agents and chemotherapy · 2023Article
- Tripartite efflux pumps of the RND superfamily: what did we learn from computational studies?Microbiology (Reading, England) · 2023Review
- The Atypical Antipsychotic Quetiapine Promotes Multiple Antibiotic Resistance in Escherichia coli.Journal of bacteriology · 2022Article
- Multidrug Resistance Pumps as a Keystone of Bacterial Resistance.Moscow University biological sciences bulletin · 2022Article
- Common recognition topology of mex transporters ofFrontiers in pharmacology · 2022Article
- Allosteric drug transport mechanism of multidrug transporter AcrB.Nature communications · 2021Article
- Cryo-EM Structure and Molecular Dynamics Analysis of the Fluoroquinolone Resistant Mutant of the AcrB Transporter fromMicroorganisms · 2020Article
- Molecular Interactions of Carbapenem Antibiotics with the Multidrug Efflux Transporter AcrB ofInternational journal of molecular sciences · 2020Article
- Permeability barriers of Gram-negative pathogens.Annals of the New York Academy of Sciences · 2020Review
- Mutations in the TolC Periplasmic Domain Affect Substrate Specificity of the AcrAB-TolC Pump.Frontiers in molecular biosciences · 2020Article
- Article
- Crystal structures of multidrug efflux pump MexB bound with high-molecular-mass compounds.Scientific reports · 2019Article
- Mapping the Dynamic Functions and Structural Features of AcrB Efflux Pump Transporter Using Accelerated Molecular Dynamics Simulations.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
2 authors.
Funding
Abstract
A major tripartite multidrug efflux pump of Escherichia coli, AcrAB-TolC, confers resistance to a wide variety of compounds. The drug molecule is captured by AcrB probably from the periplasm or the periplasm/inner membrane interface, and is passed through AcrB and then TolC to the medium. Currently, there exist numerous crystallographic and mutation data concerning the regions of AcrB and its homologues that may interact with substrates. Starting with these data, we devised fluorescence assays in whole cells to determine the entire substrate path through AcrB. We tested 48 residues in AcrB along the predicted substrate path and 25 gave positive results, based on the covalent labelling of cysteine residues by a lipophilic dye-maleimide and the blocking of Nile red efflux by covalent labelling with bulky maleimide reagents. These residues are all located in the periplasmic domain, in regions we designate as the lower part of the large external cleft, the cleft itself, the crystallographically defined binding pocket, and the gate between the pocket and the funnel. Our observations suggest that the substrate is captured in the lower cleft region of AcrB, then transported through the binding pocket, the gate and finally to the AcrB funnel that connects AcrB to TolC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.