High-resolution experimental and computational electrophysiology reveals weak β-lactam binding events in the porin PorB
| Autor: | Axel Munk, Ulrich Zachariae, Christof Kattner, Markus Schön, Florian Pein, Claudia Steinem, Annika Bartsch, Mikio Tanabe, Manuel Diehn, Salomé Llabrés |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Models
Molecular lcsh:Medicine High resolution Porins Meningitis Meningococcal Neisseria meningitidis beta-Lactams Permeability Article 03 medical and health sciences chemistry.chemical_compound Humans Binding site lcsh:Science 030304 developmental biology 0303 health sciences biology 030306 microbiology Chemistry lcsh:R Permeation biology.organism_classification Anti-Bacterial Agents Electrophysiology Porin Biophysics Lactam lcsh:Q Ampicillin Bacterial outer membrane Bacteria |
| Zdroj: | Scientific Reportsvolume Scientific Reports Scientific Reports, Vol 9, Iss 1, Pp 1-11 (2019) |
| Popis: | The permeation of most antibiotics through the outer membrane of Gram-negative bacteria occurs through porin channels. To design drugs with increased activity against Gram-negative bacteria in the face of the antibiotic resistance crisis, the strict constraints on the physicochemical properties of the permeants imposed by these channels must be better understood. Here we show that a combination of high-resolution electrophysiology, new noise-filtering analysis protocols and atomistic biomolecular simulations reveals weak binding events between the β-lactam antibiotic ampicillin and the porin PorB from the pathogenic bacteriumNeisseria meningitidis. In particular, an asymmetry often seen in the electrophysiological characteristics of ligand-bound channels is utilised to characterise the binding site and molecular interactions in detail, based on the principles of electro-osmotic flow through the channel. Our results provide a rationale for the determinants that govern the binding and permeation of zwitterionic antibiotics in anion-selective porin channels. |
| Databáze: | OpenAIRE |
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