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dc.contributor.authorLepsik, Martin
dc.contributor.authorSommer, Roman
dc.contributor.authorKuhaudomlarp, Sakonwan
dc.contributor.authorLelimousin, Mickaël
dc.contributor.authorPaci, Emanuele
dc.contributor.authorVarrot, Annabelle
dc.contributor.authorTitz, Alexander
dc.contributor.authorImberty, Anne
dc.date.accessioned2019-07-08T08:34:30Z
dc.date.available2019-07-08T08:34:30Z
dc.date.issued2019-09-01
dc.identifier.citationEur J Med Chem. 2019 Sep 1;177:212-220. doi: 10.1016/j.ejmech.2019.05.049. Epub 2019 May 18.en_US
dc.identifier.issn1768-3254
dc.identifier.pmid31146126
dc.identifier.doi10.1016/j.ejmech.2019.05.049
dc.identifier.urihttp://hdl.handle.net/10033/621850
dc.description.abstractPathogenic micro-organisms utilize protein receptors (lectins) in adhesion to host tissues, a process that in some cases relies on the interaction between lectins and human glycoconjugates. Oligosaccharide epitopes are recognized through their three-dimensional structure and their flexibility is a key issue in specificity. In this paper, we analysed by X-ray crystallography the structures of the LecB lectin from two strains of Pseudomonas aeruginosa in complex with Lewis x oligosaccharide present on cell surfaces of human tissues. An unusual conformation of the glycan was observed in all binding sites with a non-canonical syn orientation of the N-acetyl group of N-acetyl-glucosamine. A PDB-wide search revealed that such an orientation occurs only in 4% of protein/carbohydrate complexes. Theoretical chemistry calculations showed that the observed conformation is unstable in solution but stabilised by the lectin. A reliable description of LecB/Lewis x complex by force field-based methods had proven especially challenging due to the special feature of the binding site, two closely apposed Ca2+ ions which induce strong charge delocalisation. By comparing various force-field parametrisations, we propose a general strategy which will be useful in near future for designing carbohydrate-based ligands (glycodrugs) against other calcium-dependent protein receptors.en_US
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.relationnfo:eu-repo/grantAgreement/EC/H2020/795605en_US
dc.rightsembargoedAccessen_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectCalcium ionen_US
dc.subjectCarbohydrateen_US
dc.subjectLectinen_US
dc.subjectMolecular dynamicsen_US
dc.subjectN-Acetylen_US
dc.subjectQuantum effecten_US
dc.titleInduction of rare conformation of oligosaccharide by binding to calcium-dependent bacterial lectin: X-ray crystallography and modelling study.en_US
dc.typeArticleen_US
dc.contributor.departmentHIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.en_US
dc.identifier.journalEuropean Journal of Medicinal Chemistryen_US
dc.source.journaltitleEuropean journal of medicinal chemistry


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