ArticleNature communications2024
Proton-coupled transport mechanism of the efflux pump NorA.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Small-molecule inhibitors block NorA efflux by conformational trapping.Nature chemical biology · 2026Article
- Fundamentals and Advances in Programmable Peptide Hydrogels for Multifunctional Biomedical Applications: A Review.Gels (Basel, Switzerland) · 2026Review
- Nanomaterial strategies for antibiotic-resistant infections: Mechanistic frameworks, rational design, and clinical translation.Materials today. Bio · 2026Review
- Structural basis of metalloid transport by the arsenite efflux pump ArsB.Nature communications · 2026Article
- Miniprotein inhibitors of thebioRxiv : the preprint server for biology · 2026Article
- Exploring allosteric efflux pump inhibitors and the role of bacterial membrane potential in modulating drug resistance.Frontiers in microbiology · 2026Review
- Energetic and structural control of polyspecificity in a multidrug transporter.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Inhibitory potential of pentagalloyl glucose against efflux pumps inRSC advances · 2025Article
- Structural and functional insights of AmpG in muropeptide transport and multiple β-lactam antibiotics resistance.Nature communications · 2025Article
- NorA Efflux Pump Inhibitors: Expanding SAR Knowledge of Pyrazolo[4,3-c][1,2]benzothiazine 5,5-Dioxide Derivatives.Archiv der Pharmazie · 2025Article
- In Vitro and In Vivo Investigations into the Potential of Quinazoline and Quinoline Derivatives as NorA Efflux Pump Inhibitors Against ResistantAntibiotics (Basel, Switzerland) · 2025Article
- A fiducial-assisted strategy compatible with resolving small MFS transporter structures in multiple conformations using cryo-EM.Nature communications · 2025Article
- Review
- Cryo-EM characterization of the anydromuropeptide permease AmpG central to bacterial fitness and β-lactam antibiotic resistance.Nature communications · 2024Article
- Dynamics underlie the drug recognition mechanism by the efflux transporter EmrE.Nature communications · 2024Article
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Authors and funding
8 authors.
Funding
Abstract
Efflux pump antiporters confer drug resistance to bacteria by coupling proton import with the expulsion of antibiotics from the cytoplasm. Despite efforts there remains a lack of understanding as to how acid/base chemistry drives drug efflux. Here, we uncover the proton-coupling mechanism of the Staphylococcus aureus efflux pump NorA by elucidating structures in various protonation states of two essential acidic residues using cryo-EM. Protonation of Glu222 and Asp307 within the C-terminal domain stabilized the inward-occluded conformation by forming hydrogen bonds between the acidic residues and a single helix within the N-terminal domain responsible for occluding the substrate binding pocket. Remarkably, deprotonation of both Glu222 and Asp307 is needed to release interdomain tethering interactions, leading to opening of the pocket for antibiotic entry. Hence, the two acidic residues serve as a "belt and suspenders" protection mechanism to prevent simultaneous binding of protons and drug that enforce NorA coupling stoichiometry and confer antibiotic resistance.
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