ArticleThe journal of physical chemistry. B2019
Molecular Interactions of Cephalosporins with the Deep Binding Pocket of the RND Transporter AcrB.
Article in The journal of physical chemistry. B, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 25 citations in OpenAlex.
- Substrate Specificity Checkpoints of the Multidrug Efflux Pump MexF fromACS infectious diseases · 2026Article
- Computer Simulations of Multidrug Efflux Pumps of the Resistance-Nodulation-Cell Division Superfamily.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Advances in methods and concepts provide new insight into antibiotic fluxes across the bacterial membrane.Communications biology · 2024Article
- Article
- Tripartite efflux pumps of the RND superfamily: what did we learn from computational studies?Microbiology (Reading, England) · 2023Review
- A framework for dissecting affinities of multidrug efflux transporter AcrB to fluoroquinolones.Communications biology · 2022Article
- Recognition of quinolone antibiotics by the multidrug efflux transporter MexB ofPhysical chemistry chemical physics : PCCP · 2022Article
- Pyridylpiperazine-based allosteric inhibitors of RND-type multidrug efflux pumps.Nature communications · 2022Article
- Common recognition topology of mex transporters ofFrontiers in pharmacology · 2022Article
- Mechanistic Duality of Bacterial Efflux Substrates and Inhibitors: Example of Simple Substituted Cinnamoyl and Naphthyl Amides.ACS infectious diseases · 2021Article
- Chlorpromazine and Amitriptyline Are Substrates and Inhibitors of the AcrB Multidrug Efflux Pump.mBio · 2020Article
- Biosynthetic Incorporation of Site-Specific Isotopes in β-Lactam Antibiotics Enables Biophysical Studies.ACS chemical biology · 2020Article
- The challenge of intracellular antibiotic accumulation, a function of fluoroquinolone influx versus bacterial efflux.Communications biology · 2020Article
- Molecular Interactions of Carbapenem Antibiotics with the Multidrug Efflux Transporter AcrB ofInternational journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
The drug/proton antiporter AcrB, part of the major efflux pump AcrABZ-TolC in Escherichia coli, is characterized by its impressive ability to transport chemically diverse compounds, conferring a multidrug resistance phenotype. However, the molecular features differentiating between good and poor substrates of the pump have yet to be identified. In this work, we combined molecular docking with molecular dynamics simulations to study the interactions between AcrB and two representative cephalosporins, cefepime and ceftazidime (a good and poor substrate of AcrB, respectively). Our analysis revealed different binding preferences of the two compounds toward the subsites of the large deep binding pocket of AcrB. Cefepime, although less hydrophobic than ceftazidime, showed a higher affinity than ceftazidime for the so-called hydrophobic trap, a region known for binding inhibitors and substrates. This supports the hypothesis that surface complementarity between the molecule and AcrB, more than the intrinsic hydrophobicity of the antibiotic, is a feature required for the interaction within this region. Oppositely, the preference of ceftazidime for binding outside the hydrophobic trap might not be optimal for triggering allosteric conformational changes needed to the transporter to accomplish its function. Altogether, our findings could provide valuable information for the design of new antibiotics less susceptible to the efflux mechanism.
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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.