Search for glucose/galactose-binding proteins in newly discovered protein sequences using molecular modeling...

Sugar moieties serve as specificity markers in a wide variety of biochemical functions, and periplasmic glucose/galactose-binding proteins (GGBPs) serve as the primary receptors for transport and chemotaxis. Recently, complete genome sequencing projects have revealed many open reading frames for such receptors. On the basis of the homology search with the known x-ray structures (PDB ID: 3GBP/1GCA) of a periplasmic receptor protein from Salmonella typhimurium, we selected four putative proteins with amino acid identities between 30 and 48% for the prediction of three-dimensional (3D) structures of the proteins as well as their complexes with glucose and galactose. We could successfully identify the key residues involved in coordination with calcium ion spanning over two loop structures. We calculated the ligand-binding affinities and hydrogen bonding patterns of the modeled structures and compared with those of the x-ray structures. The calculation of free energies of binding of the modeled structures to glucose and galactose in the presence of water suggested that two of four putative proteins can form complexes with dissociation constants in the micromolar range (1-10 microM). Electrostatic potentials on the surfaces near the sugar and calcium-binding sites of the modeled structures were predominately negative as found in case of the x-ray structure. Taken together, our results suggest that the products of two newly discovered genes would serve as receptors for the transport of glucose and galactose.