Galectins, a family of evolutionarily conserved
animal lectins, have been shown to modulate signaling processes leading to
inflammation, apoptosis, immunoregulation, and angiogenesis through their ability to interact with
poly-N-acetyllactosamine-enriched
glycoconjugates. To date 16 human
galectin carbohydrate recognition domains have been established by sequence analysis and found to be expressed in several tissues. Given the divergent functions of these
lectins, it is of vital importance to understand common and differential features in order to search for specific inhibitors of individual members of the human
galectin family. In this work we performed an integrated computational analysis of all individual members of the human
galectin family. In the first place, we have built homology-based models for
galectin-4 and -12 N-terminus, placental
protein 13 (PP13) and PP13-like
protein for which no experimental structural information is available. We have then performed classical molecular dynamics simulations of the whole 15 members family in free and
ligand-bound states to analyze
protein and
protein-
ligand interaction dynamics. Our results show that all
galectins adopt the same fold, and the
carbohydrate recognition domains are very similar with structural differences located in specific loops. These differences are reflected in the dynamics characteristics, where mobility differences translate into entropy values which significantly influence their
ligand affinity. Thus,
ligand selectivity appears to be modulated by subtle differences in the
monosaccharide binding sites. Taken together, our results may contribute to the understanding, at a molecular level, of the structural and dynamical determinants that distinguish individual human
galectins.