Molecular Interactions of Carbapenem Antibiotics with the Multidrug Efflux Transporter AcrB of Escherichia coli
Abstract
1. Introduction
2. Results
2.1. Substrates and Inhibitors Co-Crystallized with AcrB
2.2. Carbapenems
3. Discussion
4. Materials and Methods
4.1. Molecular Docking
4.2. MD Simulations and Binding Free-Energy Calculations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
Abbreviations
AP | Access Pocket |
DP | Distal Pocket |
EG | Exit Gate |
HP-Trap | Hydrophobic Trap |
MD | Molecular Dynamics |
MDR | Multi Drug Resistance |
MIC | Minimum Inhibitory Concentration |
MW | Molecular Weight |
RMSD | Root Mean Square Displacement |
RND | Resistance Nodulation and cell Division |
TM | Transmembrane |
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Co-Crystallized AcrB Compound | ID | MW (Da) | SML | SMH | Hyd (%) | ΔGb (kcal/mol) | Contribution to ΔGb (%) Interface Cave Groove | ||
---|---|---|---|---|---|---|---|---|---|
Rhodamine-6G | RDM | 444 | 0.80 | 0.01 | 35 ± 8 | −38.3 ± 3.3 | 2 | 5 | 29 |
Minocycline | MIN | 458 | 0.80 | 0.70 | 34 ± 8 | −29.3 ± 4.8 | 1 | 5 | 53 |
MBX3132 | MBX | 495 | 0.87 | 0.63 | 30 ± 8 | −53.6 ± 4.6 | 2 | 18 | 24 |
D13-9001 | P9D | 693 | 0.96 | 0.91 | 40 ± 7 | −52.3 ± 4.9 | 2 | 22 | 25 |
Carbapenem Antibiotic | ID | MW (Da) | SML | SMH | Hyd (%) | ΔGb (kcal/mol) | Contribution to ΔGb (%) Interface Cave Groove | ||
---|---|---|---|---|---|---|---|---|---|
Faropenem | FAR | 284 | 0.45 | 0.81 | 27 ± 9 | −25.5 ± 3.5 | 12 | 31 | 5 |
Imipenem | IMI | 299 | 0.11 | 0.21 | 37 ± 13 | −25.1 ± 4.7 | 6 | 24 | 4 |
Panipenem | PAN | 339 | 0.01 | 0.80 | 50 ± 11 | −27.6 ± 5.0 | 4 | 23 | 5 |
Biapenem | BIA | 350 | 0.04 | 0.60 | 45 ± 13 | −30.5 ± 5.5 | 5 | 20 | 7 |
Meropenem | MER | 383 | 0.29 | 0.73 | 35 ± 8 | −30.8 ± 4.3 | 1 | 15 | 29 |
Doripenem | DOR | 420 | 0.35 | 0.84 | 47 ± 10 | −33.6 ± 5.5 | 0 | 14 | 33 |
Ertapenem | ERT | 475 | 0.30 | 0.51 | 42 ± 9 | −33.8 ± 7.8 | 3 | 28 | 31 |
Tomopenem | TOM | 539 | 0.01 | 0.54 | 50 ± 9 | −32.6 ± 6.7 | 0 | 15 | 12 |
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Atzori, A.; Malloci, G.; Cardamone, F.; Bosin, A.; Vargiu, A.V.; Ruggerone, P. Molecular Interactions of Carbapenem Antibiotics with the Multidrug Efflux Transporter AcrB of Escherichia coli. Int. J. Mol. Sci. 2020, 21, 860. https://doi.org/10.3390/ijms21030860
Atzori A, Malloci G, Cardamone F, Bosin A, Vargiu AV, Ruggerone P. Molecular Interactions of Carbapenem Antibiotics with the Multidrug Efflux Transporter AcrB of Escherichia coli. International Journal of Molecular Sciences. 2020; 21(3):860. https://doi.org/10.3390/ijms21030860
Chicago/Turabian StyleAtzori, Alessio, Giuliano Malloci, Francesca Cardamone, Andrea Bosin, Attilio Vittorio Vargiu, and Paolo Ruggerone. 2020. "Molecular Interactions of Carbapenem Antibiotics with the Multidrug Efflux Transporter AcrB of Escherichia coli" International Journal of Molecular Sciences 21, no. 3: 860. https://doi.org/10.3390/ijms21030860
APA StyleAtzori, A., Malloci, G., Cardamone, F., Bosin, A., Vargiu, A. V., & Ruggerone, P. (2020). Molecular Interactions of Carbapenem Antibiotics with the Multidrug Efflux Transporter AcrB of Escherichia coli. International Journal of Molecular Sciences, 21(3), 860. https://doi.org/10.3390/ijms21030860