Martin Lepsik
Univ. Grenoble Alpes, CNRS, CERMAV, 38000 Grenoble, France


Martin Lepsik, Roman Sommer, Sakonwan Kuhaudomlarp, Mickael Lelimousin, Emanuele Paci, Annabelle Varrot, Alexander Titz, Anne Imberty BioRXiv 2019 10.1101

Induction of Rare Conformation of Oligosaccharide by Binding to Calcium-dependent Bacterial Lectin: X-ray Crystallography and Modelling Study
Pathogenic micro-organisms utilize protein receptors in adhesion to host tissues, a process that in some cases relies on the interaction between lectin 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 analyse by X-ray crystallography the structures of the lectin LecB 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 2% 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 as 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 design general protocols which will be useful in near future for designing carbohydrate-based ligands (glycodrugs) against other calcium-dependent protein receptors.


ASS, CGS, GLS are ASP, CGLY and GLU from ff14SB with carboxylate atoms (C, O, O) scaled by 0.75.

CA, CL, K with frcmod are the ions scaled by 0.75. They are used in this work (recalculated GROMOS parameters for AMBER format) but they were created and used in this reference:

Martinek T., Duboué-Dijon E., Timr S., Mason P.E., Baxová K., Fischer H.E., Schmidt B., Pluharová E., Jungwirth P.
Calcium Ions in Aqueous Solutions: Accurate Force Field Description Aided by Ab Initio Molecular Dynamics and Neutron Scattering.
Journal of Chemical Physics 2018 148 222813.

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Last modified 17 Sep 2012