6R35

Structure of the LecB lectin from Pseudomonas aeruginosa strain PAO1 in complex with lewis x tetrasaccharide

Summary for 6R35

• Entry DOI: 10.2210/pdb6r35/pdb
• Related: 5A70
• Related PRD ID: PRD_900119
• Descriptor: Fucose-binding lectin PA-IIL, alpha-L-fucopyranose-(1-3)-[beta-D-galactopyranose-(1-4)]2-acetamido-2-deoxy-beta-D-glucopyranose, CALCIUM ION, ... (6 entities in total)
• Functional Keywords: lectin, carbohydrate, lewis x, lecb, sugar binding protein
• Biological source: Pseudomonas aeruginosa PAO1
• Total number of polymer chains: 4
• Total formula weight: 50066.08

Authors

Lepsik, M.,Sommer, R.,Kuhaudomlarp, S.,Lelimousin, M.,Varrot, A.,Titz, A.,Imberty, A. (deposition date: 2019-03-19, release date: 2019-06-12, Last modification date: 2024-01-24)

Primary citation

Lepsik, M.,Sommer, R.,Kuhaudomlarp, S.,Lelimousin, M.,Paci, E.,Varrot, A.,Titz, A.,Imberty, A.
Induction of rare conformation of oligosaccharide by binding to calcium-dependent bacterial lectin: X-ray crystallography and modelling study.
Eur.J.Med.Chem., 177:212-220, 2019

PubMed 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 Ca 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.

PubMed: 31146126
DOI: 10.1016/j.ejmech.2019.05.049

Experimental method

X-RAY DIFFRACTION (1.8 Å)