Mutation of Tyr137 of the universalEscherichia ...
Type de document :
Article dans une revue scientifique
PMID :
URL permanente :
Titre :
Mutation of Tyr137 of the universalEscherichia colifimbrial adhesin FimH relaxes the tyrosine gate prior to mannose binding
Auteur(s) :
Rabbani, Said [Auteur]
Université de Bâle = University of Basel [Unibas]
Krammer, Eva-Maria [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Roos, Goedele [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Zalewski, Adam [Auteur]
Université de Bâle = University of Basel [Unibas]
Preston, Roland [Auteur]
Université de Bâle = University of Basel [Unibas]
Eid, Sameh [Auteur]
Université de Bâle = University of Basel [Unibas]
Zihlmann, Pascal [Auteur]
Université de Bâle = University of Basel [Unibas]
Prévost, Martine [Auteur]
Faculté de Médecine [Bruxelles] [ULB]
Lensink, Marc [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Thompson, Andrew [Auteur]
Synchrotron SOLEIL [SSOLEIL]
Ernst, Beat [Auteur]
Université de Bâle = University of Basel [Unibas]
Bouckaert, Julie [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Université de Bâle = University of Basel [Unibas]
Krammer, Eva-Maria [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Roos, Goedele [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Zalewski, Adam [Auteur]
Université de Bâle = University of Basel [Unibas]
Preston, Roland [Auteur]
Université de Bâle = University of Basel [Unibas]
Eid, Sameh [Auteur]
Université de Bâle = University of Basel [Unibas]
Zihlmann, Pascal [Auteur]
Université de Bâle = University of Basel [Unibas]
Prévost, Martine [Auteur]
Faculté de Médecine [Bruxelles] [ULB]
Lensink, Marc [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Thompson, Andrew [Auteur]
Synchrotron SOLEIL [SSOLEIL]
Ernst, Beat [Auteur]
Université de Bâle = University of Basel [Unibas]
Bouckaert, Julie [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Titre de la revue :
IUCrJ
Nom court de la revue :
IUCrJ
Numéro :
4
Pagination :
7-23
Date de publication :
2017-01-01
ISSN :
2052-2525
Mot(s)-clé(s) en anglais :
crystals
FimH adhesin
Escherichia coli Infection
X-ray Crystallography
tyrosine gate
Molecular dynamics
heptyl mannose
protein structure
Thermodynamics
biphenyl mannose
molecular recognition
Mutation
peptide torsions
FimH adhesin
Escherichia coli Infection
X-ray Crystallography
tyrosine gate
Molecular dynamics
heptyl mannose
protein structure
Thermodynamics
biphenyl mannose
molecular recognition
Mutation
peptide torsions
Discipline(s) HAL :
Chimie/Chimie théorique et/ou physique
Sciences du Vivant [q-bio]
Sciences du Vivant [q-bio]
Résumé en anglais : [en]
The most prevalent diseases manifested byEscherichia coliare acute and recurrent bladder infections and chronic inflammatory bowel diseases such as Crohn's disease.E. coliclinical isolates express the FimH adhesin, which ...
Lire la suite >The most prevalent diseases manifested byEscherichia coliare acute and recurrent bladder infections and chronic inflammatory bowel diseases such as Crohn's disease.E. coliclinical isolates express the FimH adhesin, which consists of a mannose-specific lectin domain connectedviaa pilin domain to the tip of type 1 pili. Although the isolated FimH lectin domain has affinities in the nanomolar range for all high-mannosidic glycans, differentiation between these glycans is based on their capacity to form predominantly hydrophobic interactions within the tyrosine gate at the entrance to the binding pocket. In this study, novel crystal structures of tyrosine-gate mutants of FimH, ligand-free or in complex with heptyl α-d-O-mannopyranoside or 4-biphenyl α-d-O-mannopyranoside, are combined with quantum-mechanical calculations and molecular-dynamics simulations. In the Y48A FimH crystal structure, a large increase in the dynamics of the alkyl chain of heptyl α-d-O-mannopyranoside attempts to compensate for the absence of the aromatic ring; however, the highly energetic and stringent mannose-binding pocket of wild-type FimH is largely maintained. The Y137A mutation, on the other hand, is the most detrimental to FimH affinity and specificity: (i) in the absence of ligand the FimH C-terminal residue Thr158 intrudes into the mannose-binding pocket and (ii) ethylenediaminetetraacetic acid interacts strongly with Glu50, Thr53 and Asn136, in spite of multiple dialysis and purification steps. Upon mutation, pre-ligand-binding relaxation of the backbone dihedral angles at position 137 in the tyrosine gate and their coupling to Tyr48viathe interiorly located Ile52 form the basis of the loss of affinity of the FimH adhesin in the Y137A mutant.Lire moins >
Lire la suite >The most prevalent diseases manifested byEscherichia coliare acute and recurrent bladder infections and chronic inflammatory bowel diseases such as Crohn's disease.E. coliclinical isolates express the FimH adhesin, which consists of a mannose-specific lectin domain connectedviaa pilin domain to the tip of type 1 pili. Although the isolated FimH lectin domain has affinities in the nanomolar range for all high-mannosidic glycans, differentiation between these glycans is based on their capacity to form predominantly hydrophobic interactions within the tyrosine gate at the entrance to the binding pocket. In this study, novel crystal structures of tyrosine-gate mutants of FimH, ligand-free or in complex with heptyl α-d-O-mannopyranoside or 4-biphenyl α-d-O-mannopyranoside, are combined with quantum-mechanical calculations and molecular-dynamics simulations. In the Y48A FimH crystal structure, a large increase in the dynamics of the alkyl chain of heptyl α-d-O-mannopyranoside attempts to compensate for the absence of the aromatic ring; however, the highly energetic and stringent mannose-binding pocket of wild-type FimH is largely maintained. The Y137A mutation, on the other hand, is the most detrimental to FimH affinity and specificity: (i) in the absence of ligand the FimH C-terminal residue Thr158 intrudes into the mannose-binding pocket and (ii) ethylenediaminetetraacetic acid interacts strongly with Glu50, Thr53 and Asn136, in spite of multiple dialysis and purification steps. Upon mutation, pre-ligand-binding relaxation of the backbone dihedral angles at position 137 in the tyrosine gate and their coupling to Tyr48viathe interiorly located Ile52 form the basis of the loss of affinity of the FimH adhesin in the Y137A mutant.Lire moins >
Langue :
Anglais
Audience :
Non spécifiée
Établissement(s) :
CNRS
Université de Lille
Université de Lille
Équipe(s) de recherche :
Computational Molecular Systems Biology
Date de dépôt :
2020-02-12T15:11:22Z
2021-03-03T09:38:26Z
2021-03-03T09:38:26Z
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