Different architecture of the combining site of the two chicken galectins revealed by chemical mapping studies with synthetic ligand derivatives.
The detailed comparison of the carbohydrate-binding properties of related galectins from one organism can be facilitated by the application of an array of deliberately tailored methyl beta-lactoside derivatives. Focusing on chicken due to its expression of two galectins as a model for this approach, the combining-site architecture of the lectin from adult liver (CL-16) is apparently homologous to that previously observed for bovine galectin-1 (Solís, D., Jiménez-Barbero, J., Martín-Lomas, M., and Díaz-Mauriño, T. (1994) Eur. J. Biochem. 223, 107-114). Besides preservation of the key interactions and minor differences, the lectin from adult intestine (CL-14) is able to accommodate an axial HO-3 at the glucose moiety. Homology-based modeling enabled us to tentatively attribute the observed differences to a slightly different orientation of pivotal side chains in the binding pocket due to distinct substitutions of amino acid residues in the variable region within the carbohydrate-recognition domain. Thus, the results suggest overlapping but distinct ranges of potential ligands for the two chicken lectins and provide new information on their relationship to mammalian galectins. The described approach is suggested to be of relevance to design pharmaceuticals with enhanced selectivity to a certain member within a family of related lectins.
Solís
D
D
Instituto de Química Física Rocasolano, Consejo Superior de Investigaciones Científicas, Serrano 119, E-28006 Madrid, Spain.
Romero
A
A
Kaltner
H
H
Gabius
H J
HJ
Díaz-Mauriño
T
T
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D002645:Chickens; D017665:Hydroxyl Radical; D037102:Lectins / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D008759:Methylglycosides / Q000378:metabolism; D008969:Molecular Sequence Data
D037102:Lectins; D008024:Ligands; D008759:Methylglycosides; D017665:Hydroxyl Radical; C034207:methyl lactoside