High-resolution experimental and computational electrophysiology reveals weak β-lactam binding events in the porin PorB
2019 | journal article; research paper. A publication with affiliation to the University of Göttingen.
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High-resolution experimental and computational electrophysiology reveals weak β-lactam binding events in the porin PorB
Bartsch, A.; Llabrés, S.; Pein, F.; Kattner, C.; Schön, M.; Diehn, M. & Tanabe, M. et al. (2019)
Scientific Reports, 9(1) art. 1264. DOI: https://doi.org/10.1038/s41598-018-37066-9
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Details
- Authors
- Bartsch, Annika; Llabrés, Salomé; Pein, Florian; Kattner, Christof; Schön, Markus; Diehn, Manuel; Tanabe, Mikio; Munk, Axel ; Zachariae, Ulrich; Steinem, Claudia
- Abstract
- 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 bacterium Neisseria 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 porin channels.
- Issue Date
- 2019
- Journal
- Scientific Reports
- Project
- EXC 2067: Multiscale Bioimaging
- Working Group
- RG Munk
RG Steinem (Biomolecular Chemistry) - Language
- English