Effect of Noncanonical Amino Acids on Protein-Carbohydrate Interactions: Structure, Dynamics, and Carbohydrate Affinity of a Lectin Engineered with Fluorinated Tryptophan Analogs

Felix Tobola, Mickael Lelimousin, Annabelle Varrot, Emilie Gillon, Barbara Darnhofer, Ola Blixt, Ruth Birner-Gruenberger, Anne Imberty, Birgit Wiltschi

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)2211-2219
Number of pages9
JournalACS Chemical Biology
Volume13
Issue number8
DOIs
Publication statusPublished - 17 Aug 2018

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Lectins
Tryptophan
Carbohydrates
Amino Acids
Proteins
Ralstonia solanacearum
Synthetic Biology
Fluorination
Fluorine
Halogenation
Hydroxyl Radical
Polysaccharides
Hydrogen
Hydrogen bonds
Binding Sites
X-Rays
Ligands
Engineers
X rays

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

Cite this

Effect of Noncanonical Amino Acids on Protein-Carbohydrate Interactions : Structure, Dynamics, and Carbohydrate Affinity of a Lectin Engineered with Fluorinated Tryptophan Analogs. / Tobola, Felix; Lelimousin, Mickael; Varrot, Annabelle; Gillon, Emilie; Darnhofer, Barbara; Blixt, Ola; Birner-Gruenberger, Ruth; Imberty, Anne; Wiltschi, Birgit.

In: ACS Chemical Biology, Vol. 13, No. 8, 17.08.2018, p. 2211-2219.

Research output: Contribution to journalArticleResearchpeer-review

Tobola, Felix ; Lelimousin, Mickael ; Varrot, Annabelle ; Gillon, Emilie ; Darnhofer, Barbara ; Blixt, Ola ; Birner-Gruenberger, Ruth ; Imberty, Anne ; Wiltschi, Birgit. / Effect of Noncanonical Amino Acids on Protein-Carbohydrate Interactions : Structure, Dynamics, and Carbohydrate Affinity of a Lectin Engineered with Fluorinated Tryptophan Analogs. In: ACS Chemical Biology. 2018 ; Vol. 13, No. 8. pp. 2211-2219.
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