Molecular mechanism of substrate selectivity ...
Document type :
Article dans une revue scientifique
Permalink :
Title :
Molecular mechanism of substrate selectivity of the arginine-agmatine Antiporter AdiC
Author(s) :
Krammer, Eva Maria [Auteur]
Université libre de Bruxelles [ULB]
Gibbons, Andrew [Auteur]
Université libre de Bruxelles [ULB]
Roos, Goedele [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Prévost, Martine [Auteur]
Université libre de Bruxelles [ULB]
Université libre de Bruxelles [ULB]
Gibbons, Andrew [Auteur]
Université libre de Bruxelles [ULB]
Roos, Goedele [Auteur]

Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Prévost, Martine [Auteur]
Université libre de Bruxelles [ULB]
Journal title :
Scientific Reports
Volume number :
8
Pages :
15607
Publication date :
2018-10-23
ISSN :
2045-2322
HAL domain(s) :
Chimie/Chimie théorique et/ou physique
English abstract : [en]
The arginine-agmatine antiporter (AdiC) is a component of an acid resistance system developed by enteric bacteria to resist gastric acidity. In order to avoid neutral proton antiport, the monovalent form of arginine, about ...
Show more >The arginine-agmatine antiporter (AdiC) is a component of an acid resistance system developed by enteric bacteria to resist gastric acidity. In order to avoid neutral proton antiport, the monovalent form of arginine, about as abundant as its divalent form under acidic conditions, should be selectively bound by AdiC for transport into the cytosol. In this study, we shed light on the mechanism through which AdiC distinguishes Arg+ from Arg2+ of arginine by investigating the binding of both forms in addition to that of divalent agmatine, using a combination of molecular dynamics simulations with molecular and quantum mechanics calculations. We show that AdiC indeed preferentially binds Arg+. The weaker binding of divalent compounds results mostly from their greater tendency to remain hydrated than Arg+. Our data suggests that the binding of Arg+ promotes the deprotonation of Glu208, a gating residue, which in turn reinforces its interactions with AdiC, leading to longer residence times of Arg+ in the binding site. Although the total electric charge of the ligand appears to be the determinant factor in the discrimination process, two local interactions formed with Trp293, another gating residue of the binding site, also contribute to the selection mechanism: a cation-π interaction with the guanidinium group of Arg+ and an anion-π interaction involving Glu208.Show less >
Show more >The arginine-agmatine antiporter (AdiC) is a component of an acid resistance system developed by enteric bacteria to resist gastric acidity. In order to avoid neutral proton antiport, the monovalent form of arginine, about as abundant as its divalent form under acidic conditions, should be selectively bound by AdiC for transport into the cytosol. In this study, we shed light on the mechanism through which AdiC distinguishes Arg+ from Arg2+ of arginine by investigating the binding of both forms in addition to that of divalent agmatine, using a combination of molecular dynamics simulations with molecular and quantum mechanics calculations. We show that AdiC indeed preferentially binds Arg+. The weaker binding of divalent compounds results mostly from their greater tendency to remain hydrated than Arg+. Our data suggests that the binding of Arg+ promotes the deprotonation of Glu208, a gating residue, which in turn reinforces its interactions with AdiC, leading to longer residence times of Arg+ in the binding site. Although the total electric charge of the ligand appears to be the determinant factor in the discrimination process, two local interactions formed with Trp293, another gating residue of the binding site, also contribute to the selection mechanism: a cation-π interaction with the guanidinium group of Arg+ and an anion-π interaction involving Glu208.Show less >
Language :
Anglais
Audience :
Internationale
Popular science :
Non
Administrative institution(s) :
CNRS
Université de Lille
Université de Lille
Research team(s) :
Computational Molecular Systems Biology
Submission date :
2020-02-12T15:45:32Z
2024-02-16T10:49:56Z
2024-02-16T10:49:56Z
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