D. Solis et al., PROBING HYDROGEN-BONDING INTERACTIONS OF BOVINE HEART GALECTIN-1 AND METHYL BETA-LACTOSIDE BY USE OF ENGINEERED LIGANDS, European journal of biochemistry, 223(1), 1994, pp. 107-114
The binding of different synthetic monodeoxy, O-methyl and fluorodeoxy
derivatives of methyl beta-lactoside to galectin-1 from bovine heart
has been studied to probe the role of hydrogen bonding in the recognit
ion and binding. The energetic contributions of the hydroxyl groups of
methyl beta-lactoside directly involved in the interaction have been
estimated and the nature of the protein residues involved has been pre
dicted on the basis of the free energy data. Interpretations of the re
sults have been sustained by molecular modeling of the three-dimension
al structure of the sugars in solution. One side of the disaccharide m
olecule is not involved (HO-6 and HO-2') or only marginally involved (
HO-3') in hydrogen bonding. Moreover, O-methylation at these positions
causes an enhancement of the binding, suggesting favourable interacti
ons of the methyl groups which may come into contact with hydrophobic
residues at the periphery of the combining site. Hydrogen-bonding inte
ractions are almost exclusively restricted to the other side of the mo
lecule: the C-4' and C-6' hydroxyl groups act as donors of the stronge
st hydrogen bonds to charged groups of the lectin, while the C-3 hydro
xyl group participates in a strong hydrogen bond with a neutral group.
The results also suggest that the N-acetyl NH group in N-acetyllactos
amine, as well as the hydroxyl group at position C-2 in methyl beta-la
ctoside, are involved in a polar interaction with neutral groups of th
e combining site. This hydrogen-bonding pattern contrasts markedly wit
h that previously reported for the two galactose-specific Ricinus comm
unis lectins. The recognition of different epitopes of the same basic
structure underlies the differences in the oligosaccharide-binding spe
cificities of galectin-1 and the R. communis lectins.