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doi:10.22028/D291-39234
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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