A Biophysical Study with Carbohydrate Derivatives Explains the Molecular Basis of Monosaccharide Selectivity of the Pseudomonas aeruginosa Lectin LecB

Sommer, Roman; Exner, Thomas E.; Titz, Alexander

A Biophysical Study with Carbohydrate Derivatives Explains the Molecular Basis of Monosaccharide Selectivity of the Pseudomonas aeruginosa Lectin LecB

Dateien

Sommer_0-274909.pdfGröße: 1.28 MBDownloads: 201

Datum

2014

Open Access-Veröffentlichung

Open Access Gold

Sammlungen

Chemie

Publikationstyp

Zeitschriftenartikel

Publikationsstatus

Published

Erschienen in

PLoS ONE. 2014, 9(11), e112822. eISSN 1932-6203. Available under: doi: 10.1371/journal.pone.0112822

Zusammenfassung

The rise of resistances against antibiotics in bacteria is a major threat for public health and demands the development of novel antibacterial therapies. Infections with Pseudomonas aeruginosa are a severe problem for hospitalized patients and for patients suffering from cystic fibrosis. These bacteria can form biofilms and thereby increase their resistance towards antibiotics. The bacterial lectin LecB was shown to be necessary for biofilm formation and the inhibition with its carbohydrate ligands resulted in reduced amounts of biofilm. The natural ligands for LecB are glycosides of d-mannose and l-fucose, the latter displaying an unusual strong affinity. Interestingly, although mannosides are much weaker ligands for LecB, they do form an additional hydrogen bond with the protein in the crystal structure. To analyze the individual contributions of the methyl group in fucosides and the hydroxymethyl group in mannosides to the binding, we designed and synthesized derivatives of these saccharides. We report glycomimetic inhibitors that dissect the individual interactions of their saccharide precursors with LecB and give insight into the biophysics of binding by LecB. Furthermore, theoretical calculations supported by experimental thermodynamic data suggest a perturbed hydrogen bonding network for mannose derivatives as molecular basis for the selectivity of LecB for fucosides. Knowledge gained on the mode of interaction of LecB with its ligands at ambient conditions will be useful for future drug design.

Fachgebiet (DDC)

540 Chemie

Schlagwörter

Binding analysis, Hydrogen bonding, Thermodynamics, Mannose, Crystal structure, Free energy, Pseudomonas aeruginosa, Bacterial biofilms

Zitieren

ISO 690

SOMMER, Roman, Thomas E. EXNER, Alexander TITZ, 2014. A Biophysical Study with Carbohydrate Derivatives Explains the Molecular Basis of Monosaccharide Selectivity of the Pseudomonas aeruginosa Lectin LecB. In: PLoS ONE. 2014, 9(11), e112822. eISSN 1932-6203. Available under: doi: 10.1371/journal.pone.0112822

BibTex

@article{Sommer2014Bioph-30411,
  year={2014},
  doi={10.1371/journal.pone.0112822},
  title={A Biophysical Study with Carbohydrate Derivatives Explains the Molecular Basis of Monosaccharide Selectivity of the Pseudomonas aeruginosa Lectin LecB},
  number={11},
  volume={9},
  journal={PLoS ONE},
  author={Sommer, Roman and Exner, Thomas E. and Titz, Alexander},
  note={Article Number: e112822}
}

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