A Biophysical Study with Carbohydrate Derivatives Explains the Molecular Basis of Monosaccharide Selectivity of the Pseudomonas aeruginosa Lectin LecB.
Name:
Sommer et al_final.pdf
Size:
1.344Mb
Format:
PDF
Description:
Open Access publication
Average rating
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Star rating
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Issue Date
2014
Metadata
Show full item recordAbstract
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.Citation
A Biophysical Study with Carbohydrate Derivatives Explains the Molecular Basis of Monosaccharide Selectivity of the Pseudomonas aeruginosa Lectin LecB. 2014, 9 (11):e112822 PLoS ONEAffiliation
Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Campus C 2.3, D-66123, Saarbrücken, Germany; Department of Chemistry and Graduate School Chemical Biology, University of Konstanz, D-78457, Konstanz, Germany.Journal
PloS onePubMed ID
25415418Type
ArticleLanguage
enISSN
1932-6203ae974a485f413a2113503eed53cd6c53
10.1371/journal.pone.0112822
Scopus Count
The following license files are associated with this item:
Related articles
- Discovery of two classes of potent glycomimetic inhibitors of Pseudomonas aeruginosa LecB with distinct binding modes.
- Authors: Hauck D, Joachim I, Frommeyer B, Varrot A, Philipp B, Möller HM, Imberty A, Exner TE, Titz A
- Issue date: 2013 Aug 16
- Synthesis of mannoheptose derivatives and their evaluation as inhibitors of the lectin LecB from the opportunistic pathogen Pseudomonas aeruginosa.
- Authors: Hofmann A, Sommer R, Hauck D, Stifel J, Göttker-Schnetmann I, Titz A
- Issue date: 2015 Aug 14
- Monodisperse Sequence-Controlled α-l-Fucosylated Glycooligomers and Their Multivalent Inhibitory Effects on LecB.
- Authors: Bücher KS, Babic N, Freichel T, Kovacic F, Hartmann L
- Issue date: 2018 Dec
- Pseudomonas aeruginosa lectin LecB is located in the outer membrane and is involved in biofilm formation.
- Authors: Tielker D, Hacker S, Loris R, Strathmann M, Wingender J, Wilhelm S, Rosenau F, Jaeger KE
- Issue date: 2005 May
- Structural basis of carbohydrate recognition by the lectin LecB from Pseudomonas aeruginosa.
- Authors: Loris R, Tielker D, Jaeger KE, Wyns L
- Issue date: 2003 Aug 22