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 (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

Induction of Rare Conformation of Oligosaccharide by Binding to Calcium-dependent Bacterial Lectin: X-ray Crystallography and Modelling Study

Parameters, inputs and trajectories for 600 ns molecular dynamics of Pseudomonas aeruginosa lectin LecB in complex with Lewis x tetrasaccharide using the most promising Setup4 (see the publication)

Induction of Rare Conformation of Oligosaccharide by Binding to Calcium-dependent Bacterial Lectin: X-ray Crystallography and Modelling Study

Parameters, inputs and trajectories for 600 ns molecular dynamics of Pseudomonas aeruginosa lectin LecB in complex with Lewis x tetrasaccharide using the most promising Setup4 (see the publication).THIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV

Molecular Dynamics of CL11 and CL11-E complexes with 58rRNA

PDB files with added hydrogens, counterions and waters. *Hmass.top and *2us.netcdf are AMBER PARM7 and NETCDF files, respectively, for the imaged trajectories. *20WAT* and *4MG* files select 20 closest waters and 4 closest Mg2+ to residues 5,14,28,46,60,67 in case of CL11 and 10,21,22,24,49,51,61,63,64,67 in case of CL11-E. DX files are volumetric occupancies by VOLMAP.THIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV

DC-SIGN lectin / multivalent glycomimetics: Parametrisation and Molecular Dynamics

Parameter files and molecular dynamics snapshots/trajectories of the DC-SIGN lectin and multivalent glycomimetics are made available. 6-1 to 6-5 folder numbering refers to sections in the Supporting Information of the associated Porkolab, V, Lepsik, M et al. manuscript.THIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV

Force-Field Parameters for Tryptophan Analogues

AMBER ff99SB-compatible parameters for 7F (TRF) and 7aza (TRN) tryptophan analogues for use in molecular mechanics and molecular dynamics studie

Adenovirus 5C Hexon Molecular Dynamics Snapshots

Thirty snapshots at 20ns intervals from 600ns MD of the trimmed "upper" part of Adenovirus 5C Hexon.THIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV

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 (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