Induction of rare conformation of oligosaccharide by binding to calcium-dependent bacterial lectin: X-ray crystallography and modelling study.
dc.contributor.author | Lepsik, Martin | |
dc.contributor.author | Sommer, Roman | |
dc.contributor.author | Kuhaudomlarp, Sakonwan | |
dc.contributor.author | Lelimousin, Mickaël | |
dc.contributor.author | Paci, Emanuele | |
dc.contributor.author | Varrot, Annabelle | |
dc.contributor.author | Titz, Alexander | |
dc.contributor.author | Imberty, Anne | |
dc.date.accessioned | 2019-07-08T08:34:30Z | |
dc.date.available | 2019-07-08T08:34:30Z | |
dc.date.issued | 2019-09-01 | |
dc.identifier.citation | Eur 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.issn | 1768-3254 | |
dc.identifier.pmid | 31146126 | |
dc.identifier.doi | 10.1016/j.ejmech.2019.05.049 | |
dc.identifier.uri | http://hdl.handle.net/10033/621850 | |
dc.description.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. | en_US |
dc.language.iso | en | en_US |
dc.publisher | Elsevier | en_US |
dc.relation | nfo:eu-repo/grantAgreement/EC/H2020/795605 | en_US |
dc.rights | embargoedAccess | en_US |
dc.rights | Attribution-NonCommercial-ShareAlike 4.0 International | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | * |
dc.subject | Calcium ion | en_US |
dc.subject | Carbohydrate | en_US |
dc.subject | Lectin | en_US |
dc.subject | Molecular dynamics | en_US |
dc.subject | N-Acetyl | en_US |
dc.subject | Quantum effect | en_US |
dc.title | Induction of rare conformation of oligosaccharide by binding to calcium-dependent bacterial lectin: X-ray crystallography and modelling study. | en_US |
dc.type | Article | en_US |
dc.contributor.department | HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany. | en_US |
dc.identifier.journal | European Journal of Medicinal Chemistry | en_US |
dc.source.journaltitle | European journal of medicinal chemistry |