Evidence map›Paper›PMID 24558035›Full record

ArticleThe Journal of biological chemistry2014

β-Lactam selectivity of multidrug transporters AcrB and AcrD resides in the proximal binding pocket.

Naoki Kobayashi, Norihisa Tamura, Hendrik W van Veen, Akihito Yamaguchi, Satoshi Murakami

Abstract read
In one paragraph

Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

45 citing papers in PubMed.

  1. Cloning and Characterizing Multidrug Efflux Pumps.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  2. Article
  3. JAC-antimicrobial resistance · 2025
    Article
  4. Progression ofmBio · 2025
    Article
  5. Article
  6. Article
  7. Structural analysis of resistance-nodulation cell division transporters.Microbiology and molecular biology reviews : MMBR · 2024
    Review
  8. Review
  9. Article
  10. Crystal structures of multidrug efflux transporters fromProceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  11. Article
  12. Article
  13. Review
  14. Review
  15. Review
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Naoki KobayashiDepartment of Cell Membrane Biology, Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka 567-0047, Japan; Faculty of Pharmaceutical Science, Teikyo Heisei University, Nakano, Nakano-ku, Tokyo 164-8530, Japan; Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan.
Norihisa TamuraDepartment of Cell Membrane Biology, Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka 567-0047, Japan; Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan.
Hendrik W van VeenDepartment of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, United Kingdom.
Akihito YamaguchiDepartment of Cell Membrane Biology, Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka 567-0047, Japan; Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan.
Satoshi MurakamiDepartment of Cell Membrane Biology, Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka 567-0047, Japan; Department of Life Science, Tokyo Institute of Technology, Nagatsuta, Midori-ku, Yokohama 226-8501, Japan. Electronic address: murakami@bio.titech.ac.jp.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

β-Lactams are mainstream antibiotics that are indicated for the prophylaxis and treatment of bacterial infections. The AcrA-AcrD-TolC multidrug efflux system confers much stronger resistance on Escherichia coli to clinically relevant anionic β-lactam antibiotics than the homologous AcrA-AcrB-TolC system. Using an extensive combination of chimeric analysis and site-directed mutagenesis, we searched for residues that determine the difference in β-lactam specificity between AcrB and AcrD. We identified three crucial residues at the "proximal" (or access) substrate binding pocket. The simultaneous replacement of these residues in AcrB by those in AcrD (Q569R, I626R, and E673G) transferred the β-lactam specificity of AcrD to AcrB. Our findings indicate for the first time that the difference in β-lactam specificity between AcrB and AcrD relates to interactions of the antibiotic with residues in the proximal binding pocket.

Indexed as

Drug Resistance, Multiple, BacterialAnti-Bacterial AgentsATP-Binding Cassette, Sub-Family C Proteinsbeta-LactamsBinding SitesCarrier ProteinsCell MembraneCrystallography, X-RayEscherichia coliEscherichia coli ProteinsMembrane Transport ProteinsMutagenesis, Site-DirectedPlasmidsProtein BindingProtein ConformationProtein TransportAcrB protein, E coliAcrD protein, E coliAnti-Bacterial AgentsATP-Binding Cassette, Sub-Family C Proteinsbeta-LactamsCarrier ProteinsEscherichia coli ProteinsMembrane Transport ProteinsAntibiotic ResistanceDrug ResistanceMembrane ProteinsMembrane TransportMultidrug Transporters

Identifiers

PMID24558035
PMCPMC4036185

What OpenQuestion holds

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Registered trials

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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.