Fucose-binding Lectin from Opportunistic Pathogen Burkholderia ambifaria Binds to Both Plant and Human Oligosaccharidic Epitopes

Audfray, Aymeric; Claudinon, Julie; Abounit, Saïda; Ruvoën-Clouet, Nathalie; Larson, Göran; Smith, David F.; Wimmerová, Michaela; Pendu, Jacques Le; Römer, Winfried; Varrot, A.; Imberty, Anne

doi:10.1074/jbc.m111.314831

Cited by 101 publications

(160 citation statements)

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“…Soluble lectins with high affinity for human fucosylated oligosaccharides have been identified in Pseudomonas aeruginosa and bacteria from the Burkholderia cepacia complex such as B. cenocepacia and B. ambifaria [14]–[17]. LecB (also named PA-IIL) from P. aeruginosa is a tetrameric protein that displays an unusually strong micromolar affinity for l -fucose in a tight binding site which requires two Ca 2+ ions [18], [19].…”

Section: Introductionmentioning

confidence: 99%

“…LecB (also named PA-IIL) from P. aeruginosa is a tetrameric protein that displays an unusually strong micromolar affinity for l -fucose in a tight binding site which requires two Ca 2+ ions [18], [19]. BambL from B. ambifaria is a trimeric lectin arranged in a β-propeller fold with two similar binding sites per monomer, resulting in a hexameric arrangement of the fucose binding sites [14]. Both lectins were shown to bind to a large variety of fucosylated oligosaccharides with LecB having higher affinity for the Lewis a epitope [20] and BambL for the H-type 2 epitope [14].…”

Section: Introductionmentioning

confidence: 99%

“…BambL from B. ambifaria is a trimeric lectin arranged in a β-propeller fold with two similar binding sites per monomer, resulting in a hexameric arrangement of the fucose binding sites [14]. Both lectins were shown to bind to a large variety of fucosylated oligosaccharides with LecB having higher affinity for the Lewis a epitope [20] and BambL for the H-type 2 epitope [14]. An illustration of the two fucose-binding lectins is displayed in Figure 1.…”

Section: Introductionmentioning

confidence: 99%

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Deciphering the Glycan Preference of Bacterial Lectins by Glycan Array and Molecular Docking with Validation by Microcalorimetry and Crystallography

Topin

Arnaud²,

Sarkar³

et al. 2013

PLoS ONE

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Recent advances in glycobiology revealed the essential role of lectins for deciphering the glycocode by specific recognition of carbohydrates. Integrated multiscale approaches are needed for characterizing lectin specificity: combining on one hand high-throughput analysis by glycan array experiments and systematic molecular docking of oligosaccharide libraries and on the other hand detailed analysis of the lectin/oligosaccharide interaction by x-ray crystallography, microcalorimetry and free energy calculations. The lectins LecB from Pseudomonas aeruginosa and BambL from Burkholderia ambifaria are part of the virulence factors used by the pathogenic bacteria to invade the targeted host. These two lectins are not related but both recognize fucosylated oligosaccharides such as the histo-blood group oligosaccharides of the ABH(O) and Lewis epitopes. The specificities were characterized using semi-quantitative data from glycan array and analyzed by molecular docking with the Glide software. Reliable prediction of protein/oligosaccharide structures could be obtained as validated by existing crystal structures of complexes. Additionally, the crystal structure of BambL/Lewis x was determined at 1.6 Å resolution, which confirms that Lewis x has to adopt a high-energy conformation so as to bind to this lectin. Free energies of binding were calculated using a procedure combining the Glide docking protocol followed by free energy rescoring with the Prime/Molecular Mechanics Generalized Born Surface Area (MM-GBSA) method. The calculated data were in reasonable agreement with experimental free energies of binding obtained by titration microcalorimetry. The established predictive protocol is proposed to rationalize large sets of data such as glycan arrays and to help in lead discovery projects based on such high throughput technology.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Deciphering the Glycan Preference of Bacterial Lectins by Glycan Array and Molecular Docking with Validation by Microcalorimetry and Crystallography

Topin

Arnaud²,

Sarkar³

et al. 2013

PLoS ONE

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“…32 In other cases, the rigidity of branched oligosaccharides, such as the blood group antigens, appear to improve the binding entropy term. 33 Interestingly, PlyL, which does not contain metal ions, can complex a linear tetrasaccharide ( 3 ) with exceptional high affinity. Structural studies will be required to uncover the molecular features that account for the high affinity binding.…”

Section: Discussionmentioning

confidence: 99%

Endolysins of Bacillus anthracis Bacteriophages Recognize Unique Carbohydrate Epitopes of Vegetative Cell Wall Polysaccharides with High Affinity and Selectivity

et al. 2012

J. Am. Chem. Soc.

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Bacteriophages express endolysins which are the enzymes that hydrolyze peptidoglycan resulting in cell lysis and release of bacteriophages. Endolysins have acquired stringent substrate specificities, which have been attributed to cell wall binding domains (CBD). Although it has been realized that CBDs of bacteriophages that infect Gram-positive bacteria target cell wall carbohydrate structures, molecular mechanisms that confer selectivity are not understood. A range of oligosaccharides, derived from the secondary cell wall polysaccharides of Bacillus anthracis, has been chemically synthesized. The compounds contain an α-D-GlcNAc-(1→4)-β-D-ManNAc-(1→4)-β-D-GlcNAc backbone that is modified by various patterns of α-D-Gal and β-D-Gal branching points. The library of compounds could readily be prepared by employing a core trisaccharide modified by the orthogonal protecting groups Nα-9-fluorenylmethyloxycarbonate (Fmoc), 2-methylnaphthyl ether (Nap) and levulinoyl ester (Lev) and dimethylthexylsilyl ether (TDS) at key branching points. Dissociation constants for the binding the cell wall binding domains of the endolysins PlyL and PlyG were determined by surface plasmon resonance (SPR). It was found that the pattern of galactosylation greatly influenced binding affinities, and in particular a compound having a galactosyl moiety at C-4 of the non-reducing GlcNAc moiety bound in the low micromolar range. It is known that secondary cell wall polysaccharides of various bacilli may have both common and variable structural features and in particular differences in the pattern of galactosylation have been noted. Therefore, it is proposed that specificity of endolysins for specific bacilli is achieved by selective binding to a uniquely galactosylated core structure.

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“…In each case, the carbohydrate is bound via a buried fucose residue, which participates in a network of hydrogen bonds within a tight fucose-binding pocket. Blood group carbohydrate binding specificity has also been determined by glycan array and affinity quantified by titration microcalorimetry: strongest affinity is for H type 2 tetrasaccharide ( K D 7.5 μM) and Le y pentasaccharide ( K D 11.1 μM; Audfray et al, 2012). This binding preference indicates that BambL is more selective for blood and tissue carbohydrate determinants containing the type 2 epitope Fucα1-2Galβ1-4GlcNAc.…”

Section: Introductionmentioning

confidence: 99%

Molecular Simulations of Carbohydrates with a Fucose-Binding Burkholderia ambifaria Lectin Suggest Modulation by Surface Residues Outside the Fucose-Binding Pocket

et al. 2017

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Burkholderia ambifaria is an opportunistic respiratory pathogen belonging to the Burkholderia cepacia complex, a collection of species responsible for the rapidly fatal cepacia syndrome in cystic fibrosis patients. A fucose-binding lectin identified in the B. ambifaria genome, BambL, is able to adhere to lung tissue, and may play a role in respiratory infection. X-ray crystallography has revealed the bound complex structures for four fucosylated human blood group epitopes (blood group B, H type 1, H type 2, and Lex determinants). The present study employed computational approaches, including docking and molecular dynamics (MD), to extend the structural analysis of BambL-oligosaccharide complexes to include four additional blood group saccharides (A, Lea, Leb, and Ley) and a library of blood-group-related carbohydrates. Carbohydrate recognition is dominated by interactions with fucose via a hydrogen-bonding network involving Arg15, Glu26, Ala38, and Trp79 and a stacking interaction with Trp74. Additional hydrogen bonds to non-fucose residues are formed with Asp30, Tyr35, Thr36, and Trp74. BambL recognition is dominated by interactions with fucose, but also features interactions with other parts of the ligands that may modulate specificity or affinity. The detailed computational characterization of the BambL carbohydrate-binding site provides guidelines for the future design of lectin inhibitors.

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Fucose-binding Lectin from Opportunistic Pathogen Burkholderia ambifaria Binds to Both Plant and Human Oligosaccharidic Epitopes

Cited by 101 publications

References 49 publications

Deciphering the Glycan Preference of Bacterial Lectins by Glycan Array and Molecular Docking with Validation by Microcalorimetry and Crystallography

Deciphering the Glycan Preference of Bacterial Lectins by Glycan Array and Molecular Docking with Validation by Microcalorimetry and Crystallography

Endolysins of Bacillus anthracis Bacteriophages Recognize Unique Carbohydrate Epitopes of Vegetative Cell Wall Polysaccharides with High Affinity and Selectivity

Molecular Simulations of Carbohydrates with a Fucose-Binding Burkholderia ambifaria Lectin Suggest Modulation by Surface Residues Outside the Fucose-Binding Pocket

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