Titre :

A Novel Integrated Way for Deciphering the Glycan Code for the FimH Lectin

Auteur(s) :

Dumych, Tetiana [Auteur]
Ivan Franko National University of Lviv
Bridot, Clarisse [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Gouin, Sébastien G. [Auteur]
Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation [CEISAM]
Lensink, Marc [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Paryzhak, Solomiya [Auteur]
Ivan Franko National University of Lviv
Szunerits, Sabine [Auteur]
Institut d'Électronique, de Microélectronique et de Nanotechnologie (IEMN) - UMR 8520
Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 [IEMN]
Blossey, Ralf [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Bilyy, Rostyslav [Auteur]
Danylo Halytsky Lviv National Medical University [Lviv, Ukraine]
Bouckaert, Julie [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Krammer, Eva-Maria [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Titre de la revue :

Molecules

Numéro :

23

Pagination :

2794

Date de publication :

2018-10-28

ISSN :

1420-3049

Discipline(s) HAL :

Chimie/Chimie théorique et/ou physique

Résumé en anglais : [en]

The fimbrial lectin FimH from uro- and enteropathogenic Escherichia coli binds with nanomolar affinity to oligomannose glycans exposing Manα1,3Man dimannosides at their non-reducing end, but only with micromolar affinities ...
Lire la suite >The fimbrial lectin FimH from uro- and enteropathogenic Escherichia coli binds with nanomolar affinity to oligomannose glycans exposing Manα1,3Man dimannosides at their non-reducing end, but only with micromolar affinities to Manα1,2Man dimannosides. These two dimannoses play a significantly distinct role in infection by E. coli. Manα1,2Man has been described early on as shielding the (Manα1,3Man) glycan that is more relevant to strong bacterial adhesion and invasion. We quantified the binding of the two dimannoses (Manα1,2Man and Manα1,3Man to FimH using ELLSA and isothermal microcalorimetry and calculated probabilities of binding modes using molecular dynamics simulations. Our experimentally and computationally determined binding energies confirm a higher affinity of FimH towards the dimannose Manα1,3Man. Manα1,2Man displays a much lower binding enthalpy combined with a high entropic gain. Most remarkably, our molecular dynamics simulations indicate that Manα1,2Man cannot easily take its major conformer from water into the FimH binding site and that FimH is interacting with two very different conformers of Manα1,2Man that occupy 42% and 28% respectively of conformational space. The finding that Manα1,2Man binding to FimH is unstable agrees with the earlier suggestion that E. coli may use the Manα1,2Man epitope for transient tethering along cell surfaces in order to enhance dispersion of the infectionLire moins >

Langue :

Anglais

Audience :

Non spécifiée

Établissement(s) :

ISEN
Univ. Valenciennes
CNRS
Institut Catholique Lille
Centrale Lille
Université de Lille

Collections :

• Institut d'Électronique, de Microélectronique et de Nanotechnologie (IEMN) - UMR 8520
• Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Équipe(s) de recherche :

Computational Molecular Systems Biology

Date de dépôt :

2020-02-12T15:45:40Z
2022-11-09T11:21:57Z