Journal
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 177, Issue -, Pages 212-220Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2019.05.049
Keywords
Lectin; Carbohydrate; Calcium ion; Quantum effect; Molecular dynamics; N-Acetyl
Categories
Funding
- European Union [795605]
- ANR PIA Glyco@Alps, France [ANR-15-IDEX-02]
- Labex ARCANE
- CBH-EUR-GS, France [ANR-17-EURE-0003]
- Helmholtz Association, Germany [VH-NG-934]
- Rhone-Alpes region, France [CPER07_13 CIRA]
- Equip@Meso project [ANR-10-EQPX-29-01]
- EC Research Innovation Action under the H2020 Programme [INFRAIA-2016-1-730897]
- Marie Curie Actions (MSCA) [795605] Funding Source: Marie Curie Actions (MSCA)
Ask authors/readers for more resources
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 noncanonical 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. (C) 2019 Elsevier Masson SAS. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available