ArticleNature communications2023
Conformational restriction shapes the inhibition of a multidrug efflux adaptor protein.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
13 citing papers in PubMed, 25 citations in OpenAlex.
- From static structures to dynamic energy landscapes: the latest revolution in molecular biology.Current opinion in structural biology · 2026Review
- DeepPath: overcoming data scarcity for protein transition pathway prediction using physics-based deep learning.Chemical science · 2026Article
- Loss of DNA mismatch repair genes leads to acquisition of antibiotic resistance independent of secondary mutations.PLoS genetics · 2026Article
- A review of research progress on periplasmic adaptor proteins in bacterial tripartite pumps.Frontiers in microbiology · 2026Review
- Article
- Unveiling structural dynamics and allosteric vulnerabilities in Klebsiella pneumoniae KPHS_11890: an integrated DRKG-MD study.Journal of computer-aided molecular design · 2025Article
- Molecular basis for multidrug efflux by an anaerobic-associated RND transporter.Nature communications · 2025Article
- MgbioRxiv : the preprint server for biology · 2024Article
- Upregulation of outer membrane porin geneMicrobiology spectrum · 2024Article
- Molecular insights into the determinants of substrate specificity and efflux inhibition of the RND efflux pumps AcrB and AdeB.Microbiology (Reading, England) · 2024Review
- Mass Spectrometry Investigation of Some ATP-Binding Cassette (ABC) Proteins.Medicina (Kaunas, Lithuania) · 2024Review
- Exploring the inhibitory potential ofFrontiers in molecular biosciences · 2023Article
- A growing battlefield in the war against biofilm-induced antimicrobial resistance: insights from reviews on antibiotic resistance.Frontiers in cellular and infection microbiology · 2023Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
Membrane efflux pumps play a major role in bacterial multidrug resistance. The tripartite multidrug efflux pump system from Escherichia coli, AcrAB-TolC, is a target for inhibition to lessen resistance development and restore antibiotic efficacy, with homologs in other ESKAPE pathogens. Here, we rationalize a mechanism of inhibition against the periplasmic adaptor protein, AcrA, using a combination of hydrogen/deuterium exchange mass spectrometry, cellular efflux assays, and molecular dynamics simulations. We define the structural dynamics of AcrA and find that an inhibitor can inflict long-range stabilisation across all four of its domains, whereas an interacting efflux substrate has minimal effect. Our results support a model where an inhibitor forms a molecular wedge within a cleft between the lipoyl and αβ barrel domains of AcrA, diminishing its conformational transmission of drug-evoked signals from AcrB to TolC. This work provides molecular insights into multidrug adaptor protein function which could be valuable for developing antimicrobial therapeutics.
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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.