Structural studies on mannose-selective glycoprotein receptors using molecular modeling techniques.

Glycoproteins play important roles in various cellular events and their presence in appropriate locations in proper active conformations is essential for many biochemical functions. Recent evidences suggest that some glycoproteins may require sorting receptors for efficient exit from the endoplasmic reticulum. These receptors need the presence of calcium or other metal ions for their native activity. The three-dimensional structure of such a receptor, p58/ERGIC-53, has been recently solved by x-ray crystallography, which is a mannose-selective lectin and contains two Ca(2+) ions. Homology search in the sequence databases indicates a large number of proteins which bear varying degrees of homology in a wide spectrum of species with this receptor. In this study we have systematically searched for such genes which are potential candidates for acting as mannose-mediated glycoprotein receptors in various species as initially inferred from their amino acid sequence homology. Structures of a number of proteins have been predicted using knowledge-based homology modeling, and their ability to act as the glycoprotein receptor has been explored by examining the nature of sugar-binding site. Tetramer of mannose was docked in the binding pockets of the modeled structures followed by energy minimization and molecular dynamics to obtain 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 p58/ERGIC-53-mannose complex.