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Titel: Induction of rare conformation of oligosaccharide by binding to calcium-dependent bacterial lectin : X-ray crystallography and modelling study
VerfasserIn: Lepsik, Martin
Sommer, Roman
Kuhaudomlarp, Sakonwan
Lelimousin, Mickaël
Paci, Emanuele
Varrot, Annabelle
Titz, Alexander
Imberty, Anne
Sprache: Englisch
Titel: European Journal of Medicinal Chemistry
Bandnummer: 177
Seiten: 212-220
Verlag/Plattform: Elsevier
Erscheinungsjahr: 2019
Freie Schlagwörter: Lectin
Carbohydrate
Calcium ion
Quantum effect
Molecular dynamics
N-Acetyl
DDC-Sachgruppe: 500 Naturwissenschaften
Dokumenttyp: Journalartikel / Zeitschriftenartikel
Abstract: Pathogenic 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.
DOI der Erstveröffentlichung: 10.1016/j.ejmech.2019.05.049
URL der Erstveröffentlichung: https://doi.org/10.1016/j.ejmech.2019.05.049
Link zu diesem Datensatz: urn:nbn:de:bsz:291--ds-392343
hdl:20.500.11880/35356
http://dx.doi.org/10.22028/D291-39234
ISSN: 0223-5234
Datum des Eintrags: 6-Mär-2023
Fakultät: NT - Naturwissenschaftlich- Technische Fakultät
Fachrichtung: NT - Chemie
Professur: NT - Univ.-Prof. Dr. phil. Alexander Titz
Sammlung:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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