Evidence map›Paper›PMID 37458117›Full record

ArticleThe EMBO journal2023

Cryo-EM structure of antibacterial efflux transporter QacA from Staphylococcus aureus reveals a novel extracellular loop with allosteric role.

Puja Majumder, Shahbaz Ahmed, Pragya Ahuja, Arunabh Athreya, Rakesh Ranjan, Aravind Penmatsa

Open access · hybridAbstract read
In one paragraph

Article in The EMBO journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.2field-weighted citation impact, top 22% of its field
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

11 citing papers in PubMed, 13 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Highly Effective Biocides againstACS infectious diseases · 2024
    Article
  8. Structure and function ofProceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  9. Article
  10. Article
  11. 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

6 authors at 2 institutions in 1 country.

Puja MajumderMolecular Biophysics Unit, Indian Institute of Science, Bangalore, India.ORCID 0000-0002-5421-6814
Shahbaz Ahmed *Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India.
Pragya Ahuja *Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India.ORCID 0000-0001-7005-3384
Arunabh Athreya *Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India.ORCID 0000-0003-2133-2795
Rakesh RanjanICAR-National Research Centre on Camel, Jorbeer, Bikaner, India.ORCID 0000-0002-5849-6016
Aravind PenmatsaMolecular Biophysics Unit, Indian Institute of Science, Bangalore, India.ORCID 0000-0001-9519-5055
Indian Institute of Science Bangalore · INNational Research Centre on Camel · IN

Funding

Biotechnology and Biological Sciences Research CouncilDBT-Wellcome Trust India Alliance IA/I/15/2/502063Medical Research CouncilWellcome Trust
6 · The paper itself

Abstract

Efflux of antibacterial compounds is a major mechanism for developing antimicrobial resistance. In the Gram-positive pathogen Staphylococcus aureus, QacA, a 14 transmembrane helix containing major facilitator superfamily antiporter, mediates proton-coupled efflux of mono and divalent cationic antibacterial compounds. In this study, we report the cryo-EM structure of QacA, with a single mutation D411N that improves homogeneity and retains efflux activity against divalent cationic compounds like dequalinium and chlorhexidine. The structure of substrate-free QacA, complexed to two single-domain camelid antibodies, was elucidated to a resolution of 3.6 Å. The structure displays an outward-open conformation with an extracellular helical hairpin loop (EL7) between transmembrane helices 13 and 14, which is conserved in a subset of DHA2 transporters. Removal of the EL7 hairpin loop or disrupting the interface formed between EL7 and EL1 compromises efflux activity. Chimeric constructs of QacA with a helical hairpin and EL1 grafted from other DHA2 members, LfrA and SmvA, restore activity in the EL7 deleted QacA revealing the allosteric and vital role of EL7 hairpin in antibacterial efflux in QacA and related members.

Indexed as

Staphylococcal InfectionsStaphylococcus aureusAnti-Bacterial AgentsBacterial ProteinsCryoelectron MicroscopyHumansMembrane Transport ProteinsAnti-Bacterial AgentsBacterial ProteinsMembrane Transport Proteinsantibacterial effluxdrug:proton antiportIndian camelid antibodiesQacARocker-switch

Identifiers

PMID37458117
PMCPMC10425836
OpenAlexW4384493015

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.