ArticleScientific reports2017
Molecular Rationale behind the Differential Substrate Specificity of Bacterial RND Multi-Drug Transporters.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed.
- Environment-dependent epistasis shapes adaptation to fluctuating resources.bioRxiv : the preprint server for biology · 2026Article
- Molecular mechanism of transition-state inhibitors of bacterial antibiotic efflux pumps.npj antimicrobials and resistance · 2026Article
- Molecular basis for multidrug efflux by an anaerobic-associated RND transporter.Nature communications · 2025Article
- Efflux-Mediated Resistance inAntibiotics (Basel, Switzerland) · 2025Review
- Advances in methods and concepts provide new insight into antibiotic fluxes across the bacterial membrane.Communications biology · 2024Article
- Structural and functional diversity of Resistance-Nodulation-Division (RND) efflux pump transporters with implications for antimicrobial resistance.Microbiology and molecular biology reviews : MMBR · 2024Review
- Structural analysis of resistance-nodulation cell division transporters.Microbiology and molecular biology reviews : MMBR · 2024Review
- Molecular insights into the determinants of substrate specificity and efflux inhibition of the RND efflux pumps AcrB and AdeB.Microbiology (Reading, England) · 2024Review
- Deorphanizing solute carriers inFrontiers in microbiology · 2024Article
- Identification and Characterization of a Novel Major Facilitator Superfamily Efflux Pump, SA09310, Mediating Tetracycline Resistance in Staphylococcus aureus.Antimicrobial agents and chemotherapy · 2023Article
- Tripartite efflux pumps of the RND superfamily: what did we learn from computational studies?Microbiology (Reading, England) · 2023Review
- AcrAB efflux pump impacts on the survival of adherent-invasive Escherichia coli strain LF82 inside macrophages.Scientific reports · 2023Article
- Article
- A genetic platform to investigate the functions of bacterial drug efflux pumps.Nature chemical biology · 2022Article
- Spatial Characteristics of the Efflux Pump MexB Determine Inhibitor Binding.Antimicrobial agents and chemotherapy · 2022Article
- The role of bacterial transport systems in the removal of host antimicrobial peptides in Gram-negative bacteria.FEMS microbiology reviews · 2022Review
- Common recognition topology of mex transporters ofFrontiers in pharmacology · 2022Article
- Efflux Pump Mediated Antimicrobial Resistance by Staphylococci in Health-Related Environments: Challenges and the Quest for Inhibition.Antibiotics (Basel, Switzerland) · 2021Review
- Characterization and Molecular Determinants for β-Lactam Specificity of the Multidrug Efflux Pump AcrD fromAntibiotics (Basel, Switzerland) · 2021Article
- Article
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5 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Resistance-Nodulation-cell Division (RND) transporters AcrB and AcrD of Escherichia coli expel a wide range of substrates out of the cell in conjunction with AcrA and TolC, contributing to the onset of bacterial multidrug resistance. Despite sharing an overall sequence identity of ~66% (similarity ~80%), these RND transporters feature distinct substrate specificity patterns whose underlying basis remains elusive. We performed exhaustive comparative analyses of the putative substrate binding pockets considering crystal structures, homology models and conformations extracted from multi-copy μs-long molecular dynamics simulations of both AcrB and AcrD. The impact of physicochemical and topographical properties (volume, shape, lipophilicity, electrostatic potential, hydration and distribution of multi-functional sites) within the pockets on their substrate specificities was quantitatively assessed. Differences in the lipophilic and electrostatic potentials among the pockets were identified. In particular, the deep pocket of AcrB showed the largest lipophilicity convincingly pointing out its possible role as a lipophilicity-based selectivity filter. Furthermore, we identified dynamic features (not inferable from sequence analysis or static structures) such as different flexibilities of specific protein loops that could potentially influence the substrate recognition and transport profile. Our findings can be valuable for drawing structure (dynamics)-activity relationship to be employed in drug design.
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