Unraveling Sugar Binding Modes to DC-SIGN by Employing Fluorinated Carbohydrates
A fluorine nuclear magnetic resonance (F-19-NMR)-based method is employed to assess the binding preferences and interaction details of a library of synthetic fluorinated monosaccharides towards dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN), a lectin of bio...
| Autores: | , , , , , , , , , |
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| Tipo de documento: | artigo |
| Data de publicação: | 2019 |
| País: | España |
| Recursos: | Universidad del País Vasco |
| Repositório: | Addi. Archivo Digital para la Docencia y la Investigación |
| OAI Identifier: | oai:addi.ehu.eus:10810/40566 |
| Acesso em linha: | http://hdl.handle.net/10810/40566 |
| Access Level: | Acceso aberto |
| Palavra-chave: | NMR molecular recognition lectin glycomimetics DC-SIGN C-type lectins fluorinated sugars F-19-NMR screening molecular dynamics transfer difference NMR structural basis recognition protein ligand parameters langerin glycans |
| Resumo: | A fluorine nuclear magnetic resonance (F-19-NMR)-based method is employed to assess the binding preferences and interaction details of a library of synthetic fluorinated monosaccharides towards dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN), a lectin of biomedical interest, which is involved in different viral infections, including HIV and Ebola, and is able to recognize a variety of self- and non-self-glycans. The strategy employed allows not only screening of a mixture of compounds, but also obtaining valuable information on the specific sugar-protein interactions. The analysis of the data demonstrates that monosaccharides Fuc, Man, Glc, and Gal are able to bind DC-SIGN, although with decreasing affinity. Moreover, a new binding mode between Man moieties and DC-SIGN, which might have biological implications, is also detected for the first time. The combination of the F-19 with standard proton saturation transfer difference (H-1-STD-NMR) data, assisted by molecular dynamics (MD) simulations, permits us to successfully define this new binding epitope, where Man coordinates a Ca2+ ion of the lectin carbohydrate recognition domain (CRD) through the axial OH-2 and equatorial OH-3 groups, thus mimicking the Fuc/DC-SIGN binding architecture. |
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