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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F22%3A00556399" target="_blank" >RIV/61388963:_____/22:00556399 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.1002/cbic.202100593" target="_blank" >https://doi.org/10.1002/cbic.202100593</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/cbic.202100593" target="_blank" >10.1002/cbic.202100593</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Chembiochem

ISSN

1439-4227

e-ISSN

1439-7633

Svazek periodika

23

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

7

Strana od-do

e202100593

Kód UT WoS článku

000744320500001

EID výsledku v databázi Scopus

2-s2.0-85122926859