Effect of Noncanonical Amino Acids on Protein–Carbohydrate Interactions: Structure, Dynamics, and Carbohydrate Affinity of a Lectin Engineered with Fluorinated Tryptophan Analogs
| Autor: | Tobola, F., Lelimousin, M., Varrot, A., Gillon, E., Darnhofer, B., Blixt, O., Birner-Gruenberger, R., Imberty, A., Wiltschi, B. |
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| Přispěvatelé: | Centre de Recherches sur les Macromolécules Végétales (CERMAV ), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]) |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: | |
| Zdroj: | ACS Chemical Biology ACS Chemical Biology, American Chemical Society, 2018, 13 (8), pp.2211-2219. ⟨10.1021/acschembio.8b00377⟩ 'ACS Chemical Biology ', vol: 13, pages: 2211-2219 (2018) |
| ISSN: | 1554-8937 1554-8929 |
| Popis: | International audience; Protein−carbohydrate interactions play crucial roles in biology. Understanding and modifying these interactions is of major interest for fighting many diseases. We took a synthetic biology approach and incorporated noncanonical amino acids into a bacterial lectin to modulate its interactions with carbohydrates. We focused on tryptophan, which is prevalent in carbohydrate binding sites. The exchange of the tryptophan residues with analogs fluorinated at different positions resulted in three distinctly fluorinated variants of the lectin from Ralstonia solanacearum. We observed differences in stability and affinity toward fucosylated glycans and rationalized them by X-ray and modeling studies. While fluorination decreased the aromaticity of the indole ring and, therefore, the strength of carbohydrate−aromatic interactions, additional weak hydrogen bonds were formed between fluorine and the ligand hydroxyl groups. Our approach opens new possibilities to engineer carbohydrate receptors |
| Databáze: | OpenAIRE |
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