Engineering the Ligand Specificity of the Human Galectin-1 by Incorporation of Tryptophan Analogues

0556399 - ÚOCHB 2023 RIV DE eng J - Článek v odborném periodiku
Tobola, F. - Lepšík, Martin - Zia, S. R. - Leffler, H. - Nilsson, U. J. - Blixt, O. - Imberty, A. - Wiltschi, B.
Engineering the Ligand Specificity of the Human Galectin-1 by Incorporation of Tryptophan Analogues.
Chembiochem. Roč. 23, č. 5 (2022), č. článku e202100593. ISSN 1439-4227. E-ISSN 1439-7633
Institucionální podpora: RVO:61388963
Klíčová slova: lectins * molecular dynamic * non-canonical amino acids * protein engineering * synthetic glycobiolog
Obor OECD: Biochemistry and molecular biology
Impakt faktor: 3.2, rok: 2022
Způsob publikování: Omezený přístup
https://doi.org/10.1002/cbic.202100593

Galectin-1 is a beta-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.
Trvalý link: http://hdl.handle.net/11104/0331096