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Computer simulation of spermine-porin channel interactions
Stéphanie Vidal1, Pierre Brouant, Jacqueline Chevalier
1GERCTOP, UMR CNRS 6009, Université de la Méditerranée, 13385 Marseille, France.
Abstract:
Porin channels play a prominent role during fluoroquinolone uptake and spermine strongly alters the diffusion rate of norfloxacine. Consequently the interactions between spermine and bacterial porin were studied by computer simulation. The results indicate that various residues (E62, D 113, E 117,...) closely located in the internal eyelet region of the OmpF channel are potential binding sites. Among them, the D 113 residue, seems to play an important role in the association channel-spermine. This interaction introduces several changes in the internal morphology of the channel which are responsible for the inhibition of antibiotic uptake using the porin route.
Insights
Spermine binding to bacterial porin channels, like OmpF, significantly impacts antibiotic diffusion. Computer simulations reveal specific residues, particularly D113, are key to this interaction, inhibiting fluoroquinolone uptake.
Area of Science:
- Microbiology
- Biophysics
- Computational Chemistry
Background:
- Porin channels are crucial for bacterial outer membrane permeability.
- Fluoroquinolone antibiotics rely on porins for cellular entry.
- Spermine is a polyamine that can modulate transport across membranes.
Purpose of the Study:
- To investigate the molecular interactions between spermine and bacterial porin channels.
- To understand how spermine affects the diffusion of antibiotics like norfloxacin through porins.
Main Methods:
- Utilized computer simulations to model spermine-porin interactions.
- Analyzed the structural changes within the OmpF porin channel upon spermine binding.
Main Results:
- Identified potential spermine binding sites within the OmpF channel, including residues E62, D113, and E117.
- The D113 residue was highlighted as a critical site for spermine association.
- Spermine binding induced conformational changes in the porin's internal structure, hindering antibiotic passage.
Conclusions:
- Spermine binding to bacterial porins inhibits antibiotic uptake by altering channel morphology.
- The D113 residue plays a significant role in the spermine-porin interaction and subsequent inhibition of norfloxacin diffusion.