Prediction of 3-D structures of fucose-binding proteins and structural analysis of their interaction with ligands

The importance of fucose-binding proteins stems from the presence of fucose as terminal sugars in H and Lewis (a) blood groups. Recently, the structure of a complex between Anguilla anguilla agglutinin (AAA) and alpha-L-fucose has been worked out at 1.9 A resolution. The structure of AAA characterizes the novel fold of an entire lectin family. In the present study, molecular modeling techniques have been used to identify new proteins that can provide a similar fucose binding module in the newly discovered genomic sequences using the above mentioned structural information. We modeled 3-D structures of three such proteins, namely, ebiP5322 protein of Anopheles gambiae, a pentraxin of Xenopus laevis, and the fw gene product of Drosophila melanogaster. alpha-L-fucose was docked in the binding pockets of the modeled structures followed by energy minimization and molecular dynamic runs to obtain the most probable structures of the complexes. Properties of these modeled complexes were studied to examine the nature of physicochemical forces involved in the complex formation and compared with AAA-alpha-L-fucose complex. It was found that ebiP5322 protein of A. gambiae and the pentraxin of X. laevis can provide a fucose-binding fold similar to AAA. We studied structures of four protein-fucose complexes to examine the electrostatic potential surfaces around the binding site and concluded that a highly positive-charged surface was not a necessary condition of fucose-binding.