Titre :

Sites for Dynamic Protein-Carbohydrate Interactions of O- and C-Linked Mannosides on the E. coli FimH Adhesin

Auteur(s) :

Touaibia, Mohamed [Auteur]
Université de Moncton
Krammer, Eva-Maria [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Shiao, Tze [Auteur]
Département de Chimie [Montréal]
Université du Québec à Montréal = University of Québec in Montréal [UQAM]
Yamakawa, Nao [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Wang, Qingan [Auteur]
Université du Québec à Montréal = University of Québec in Montréal [UQAM]
Glinschert, Anja [Auteur]
University College Dublin [Dublin] [UCD]
Papadopoulos, Alex [Auteur]
Université du Québec à Montréal = University of Québec in Montréal [UQAM]
Mousavifar, Leila [Auteur]
Université du Québec à Montréal = University of Québec in Montréal [UQAM]
Maes, Emmanuel [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Oscarson, Stefan [Auteur]
University College Dublin [Dublin] [UCD]
Vergoten, Gerard [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Lensink, Marc [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Roy, René [Auteur]
Université du Québec à Montréal = University of Québec in Montréal [UQAM]
Bouckaert, Julie [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Titre de la revue :

Molecules

Numéro :

22

Pagination :

1101

Éditeur :

MDPI

Date de publication :

2017-07-03

ISSN :

1420-3049

Mot(s)-clé(s) en anglais :

Fimbriae Proteins
Mannosides
Adhesins, Escherichia coli
Escherichia coli
Models, Molecular
Structure-Activity Relationship
dynamic binding
Molecular Dynamics Simulation
Anti-adhesive
C-glycosidic linkage
uropathogenic E. coli
Bacterial Adhesion
Protein Binding
Protein Conformation
clamp loop
Binding Sites
ortho-biphenyl mannose
FimH

Discipline(s) HAL :

Chimie/Chimie théorique et/ou physique

Résumé en anglais : [en]

Antagonists of the Escherichia coli type-1 fimbrial adhesin FimH are recognized as attractive alternatives for antibiotic therapies and prophylaxes against acute and recurrent bacterial infections. In this study ...
Lire la suite >Antagonists of the Escherichia coli type-1 fimbrial adhesin FimH are recognized as attractive alternatives for antibiotic therapies and prophylaxes against acute and recurrent bacterial infections. In this study α-d-mannopyranosides O- or C-linked with an alkyl, alkene, alkyne, thioalkyl, amide, or sulfonamide were investigated to fit a hydrophobic substituent with up to two aryl groups within the tyrosine gate emerging from the mannose-binding pocket of FimH. The results were summarized into a set of structure-activity relationships to be used in FimH-targeted inhibitor design: alkene linkers gave an improved affinity and inhibitory potential, because of their relative flexibility combined with a favourable interaction with isoleucine-52 located in the middle of the tyrosine gate. Of particular interest is a C-linked mannoside, alkene-linked to an ortho-substituted biphenyl that has an affinity similar to its O-mannosidic analog but superior to its para-substituted analog. Docking of its high-resolution NMR solution structure to the FimH adhesin indicated that its ultimate, ortho-placed phenyl ring is able to interact with isoleucine-13, located in the clamp loop that undergoes conformational changes under shear force exerted on the bacteria. Molecular dynamics simulations confirmed that a subpopulation of the C-mannoside conformers is able to interact in this secondary binding site of FimHLire moins >

Langue :

Anglais

Audience :

Internationale

Établissement(s) :

CNRS
Université de Lille

Collections :

• Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Équipe(s) de recherche :

Diversité structurale des héparanes sulfates et régulation de la réponse inflammatoire
Computational Molecular Systems Biology

Date de dépôt :

2020-02-12T15:12:34Z
2023-02-01T09:09:06Z