Engineering the Ligand Specificity of the Human Galectin-1 by Incorporation of Tryptophan Analogues
(2022) In ChemBioChem 23(5).- Abstract
Galectin-1 is a β-galactoside-binding lectin with manifold biological functions. A single tryptophan residue (W68) in its carbohydrate binding site plays a major role in ligand binding and is highly conserved among galectins. To fine tune galectin-1 specificity, we introduced several non-canonical tryptophan analogues at this position of human galectin-1 and analyzed the resulting variants using glycan microarrays. Two variants containing 7-azatryptophan and 7-fluorotryptophan showed a reduced affinity for 3’-sulfated oligosaccharides. Their interaction with different ligands was further analyzed by fluorescence polarization competition assay. Using molecular modeling we provide structural clues that the change in affinities comes from... (More)
Galectin-1 is a β-galactoside-binding lectin with manifold biological functions. A single tryptophan residue (W68) in its carbohydrate binding site plays a major role in ligand binding and is highly conserved among galectins. To fine tune galectin-1 specificity, we introduced several non-canonical tryptophan analogues at this position of human galectin-1 and analyzed the resulting variants using glycan microarrays. Two variants containing 7-azatryptophan and 7-fluorotryptophan showed a reduced affinity for 3’-sulfated oligosaccharides. Their interaction with different ligands was further analyzed by fluorescence polarization competition assay. Using molecular modeling we provide structural clues that the change in affinities comes from modulated interactions and solvation patterns. Thus, we show that the introduction of subtle atomic mutations in the ligand binding site of galectin-1 is an attractive approach for fine-tuning its interactions with different ligands.
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- author
- Tobola, Felix ; Lepšík, Martin ; Zia, Syeda Rehana ; Leffler, Hakon LU ; Nilsson, Ulf J. LU ; Blixt, Ola ; Imberty, Anne and Wiltschi, Birgit
- organization
- publishing date
- 2022
- type
- Contribution to journal
- publication status
- published
- subject
- in
- ChemBioChem
- volume
- 23
- issue
- 5
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- scopus:85122926859
- pmid:34978765
- ISSN
- 1439-4227
- DOI
- 10.1002/cbic.202100593
- language
- English
- LU publication?
- yes
- id
- 40fd01c3-03a0-4096-ba33-28bacfb00027
- date added to LUP
- 2022-02-24 15:20:29
- date last changed
- 2024-05-04 15:42:57
@article{40fd01c3-03a0-4096-ba33-28bacfb00027,
abstract = {{<p>Galectin-1 is a β-galactoside-binding lectin with manifold biological functions. A single tryptophan residue (W68) in its carbohydrate binding site plays a major role in ligand binding and is highly conserved among galectins. To fine tune galectin-1 specificity, we introduced several non-canonical tryptophan analogues at this position of human galectin-1 and analyzed the resulting variants using glycan microarrays. Two variants containing 7-azatryptophan and 7-fluorotryptophan showed a reduced affinity for 3’-sulfated oligosaccharides. Their interaction with different ligands was further analyzed by fluorescence polarization competition assay. Using molecular modeling we provide structural clues that the change in affinities comes from modulated interactions and solvation patterns. Thus, we show that the introduction of subtle atomic mutations in the ligand binding site of galectin-1 is an attractive approach for fine-tuning its interactions with different ligands.</p>}},
author = {{Tobola, Felix and Lepšík, Martin and Zia, Syeda Rehana and Leffler, Hakon and Nilsson, Ulf J. and Blixt, Ola and Imberty, Anne and Wiltschi, Birgit}},
issn = {{1439-4227}},
language = {{eng}},
number = {{5}},
publisher = {{John Wiley & Sons Inc.}},
series = {{ChemBioChem}},
title = {{Engineering the Ligand Specificity of the Human Galectin-1 by Incorporation of Tryptophan Analogues}},
url = {{http://dx.doi.org/10.1002/cbic.202100593}},
doi = {{10.1002/cbic.202100593}},
volume = {{23}},
year = {{2022}},
}