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Title: Molecular simulations of carbohydrates with a fucose-binding Burkholderia ambifaria Lectin suggest modulation by surface residues outside the fucose-binding pocket
Austin Authors: Dingjan, Tamir;Imberty, Anne;Pérez, Serge;Yuriev, Elizabeth;Ramsland, Paul A 
Affiliation: Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Victoria, Australia
Centre de Recherches sur les Macromolécules Végétales, Centre National de la Recherche Scientifique, Université Grenoble Alpes, Grenoble, France
Département de Pharmacochimie Moléculaire, Centre National de la Recherche Scientifique, Université Grenoble Alpes, Grenoble, France
School of Science, RMIT University, Melbourne, Victoria, Australia
Department of Surgery, Austin Health, University of Melbourne, Heidelberg, Victoria, Australia
Department of Immunology, Central Clinical School, Monash University, Melbourne, , Victoria, Australia
Burnet Institute, Melbourne, Victoria, Australia
Issue Date: 21-Jun-2017
Date: 2017-06-21
Publication information: Frontiers in Pharmacology 2017; 8: 393
Abstract: 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.
DOI: 10.3389/fphar.2017.00393
Journal: Frontiers in Pharmacology
PubMed URL:
Type: Journal Article
Subjects: Burkholderia ambifaria
Blood group determinants
Molecular dynamics
Appears in Collections:Journal articles

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