Facilitated Permeation of Antibiotics across Membrane Channels − Interaction of the Quinolone Moxifloxacin with the OmpF Channel
| Autor: | Patrícia Neves, Tivadar Mach, Matteo Ceccarelli, Helge Weingart, Mathias Winterhalter, Enrico Spiga, Paula Gameiro, Paolo Ruggerone |
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| Rok vydání: | 2008 |
| Předmět: |
Models
Molecular Nalidixic acid Moxifloxacin Analytical chemistry Porins Quinolones RESONANCE ENERGY-TRANSFER Biochemistry Catalysis Molecular dynamics Colloid and Surface Chemistry medicine Lipid bilayer Aza Compounds Quenching (fluorescence) Chemistry LARGE UNILAMELLAR LIPOSOMES COLI OUTER-MEMBRANE Conductance General Chemistry Permeation Anti-Bacterial Agents Protein Structure Tertiary Spectrometry Fluorescence ESCHERICHIA-COLI SITE-DIRECTED MUTAGENESIS Quinolines Biophysics Membrane channel Fluoroquinolones Protein Binding medicine.drug |
| Zdroj: | Journal of the American Chemical Society 130 (2008): 13301–13309. doi:10.1021/ja803188c info:cnr-pdr/source/autori:Mach, T; Neves, P; Spiga, E; Weingart, H; Winterhalter, M; Ruggerone, P; Ceccarelli, M; Gameiro, P/titolo:Facilitated permeation of antibiotics across membrane channels-Interaction of the quinolone moxifloxacin with the OmpF channel/doi:10.1021%2Fja803188c/rivista:Journal of the American Chemical Society (Print)/anno:2008/pagina_da:13301/pagina_a:13309/intervallo_pagine:13301–13309/volume:130 |
| ISSN: | 1520-5126 0002-7863 |
| DOI: | 10.1021/ja803188c |
| Popis: | The facilitated influx of moxifloxacin through the most abundant channel in the outer cell wall of gram-negative bacteria was investigated. Molecular modeling provided atomic details of the interaction with the channel surface, revealed the preferred orientation of the antibiotic along its pathway, and gave an estimated time necessary for translocation. High-resolution conductance measurements on single OmpF trimers allowed the passages of individual moxifloxacin molecules to be counted. The average mean residence time of 50 micros is in agreement with the predicted strong interaction from the modeling. In contrast, control measurements with nalidixic acid, a hydrophobic antibiotic that rather permeates across the lipid membrane, revealed a negligible interaction. The spectral overlap of tryptophan with moxifloxacin was suitable for a FRET study of the protein-antibiotic interaction. Combining molecular dynamics simulations with selective quenching identified an interaction of moxifloxacin with Trp61 inside the OmpF channel, whereas nalidixic acid showed preferential interaction with Trp214 on the channel exterior. An understanding of the detailed molecular interactions between the antibiotic and its preferred channel may be used to develop new antibiotics with improved uptake kinetics. |
| Databáze: | OpenAIRE |
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