Molecular simulations of carbohydrates with a fucose-binding Burkholderia ambifaria lectin suggest modulation by surface residues outside the fucose-binding pocket

Tamir Dingjan, Anne Imberty, Serge Pérez, Elizabeth Yuriev, Paul A. Ramsland

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (Scopus)

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.

Original languageEnglish
Article number393
JournalFrontiers in Pharmacology
Volume8
Issue numberJUN
DOIs
Publication statusPublished - 21 Jun 2017

Keywords

  • Blood group determinants
  • Burkholderia ambifaria
  • Docking
  • Fucose
  • Molecular dynamics

Cite this

@article{071506a440d6474ba62a6aa92f59be3a,
title = "Molecular simulations of carbohydrates with a fucose-binding Burkholderia ambifaria lectin suggest modulation by surface residues outside the fucose-binding pocket",
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.",
keywords = "Blood group determinants, Burkholderia ambifaria, Docking, Fucose, Molecular dynamics",
author = "Tamir Dingjan and Anne Imberty and Serge P{\'e}rez and Elizabeth Yuriev and Ramsland, {Paul A.}",
year = "2017",
month = "6",
day = "21",
doi = "10.3389/fphar.2017.00393",
language = "English",
volume = "8",
journal = "Frontiers in Pharmacology",
issn = "1663-9812",
publisher = "Frontiers Media",
number = "JUN",

}

Molecular simulations of carbohydrates with a fucose-binding Burkholderia ambifaria lectin suggest modulation by surface residues outside the fucose-binding pocket. / Dingjan, Tamir; Imberty, Anne; Pérez, Serge; Yuriev, Elizabeth; Ramsland, Paul A.

In: Frontiers in Pharmacology, Vol. 8, No. JUN, 393, 21.06.2017.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Molecular simulations of carbohydrates with a fucose-binding Burkholderia ambifaria lectin suggest modulation by surface residues outside the fucose-binding pocket

AU - Dingjan, Tamir

AU - Imberty, Anne

AU - Pérez, Serge

AU - Yuriev, Elizabeth

AU - Ramsland, Paul A.

PY - 2017/6/21

Y1 - 2017/6/21

N2 - 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.

AB - 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.

KW - Blood group determinants

KW - Burkholderia ambifaria

KW - Docking

KW - Fucose

KW - Molecular dynamics

UR - http://www.scopus.com/inward/record.url?scp=85021071950&partnerID=8YFLogxK

U2 - 10.3389/fphar.2017.00393

DO - 10.3389/fphar.2017.00393

M3 - Article

VL - 8

JO - Frontiers in Pharmacology

JF - Frontiers in Pharmacology

SN - 1663-9812

IS - JUN

M1 - 393

ER -