Prediction of three-dimensional structures of enzyme-substrate and enzyme-inhibitor complexes of lysozyme.

Abstract

Conformational energy calculations were used to predict the 3-dimensional structures of enzyme-substrate and enzyme-inhibitor complexes of lysozyme. A global search method, involving the use of a disaccharide fragment molecule, was used initially to determine all favorable binding regions at the active site. The binding of a series of (nonfragmented)oligomers of N-acetylglucosamine is highly specific. The enzyme recognizes only 1 backbone conformation of the oligomer, corresponding to a left-handed helix. For saccharides containing 2 or more N-acetylglucosamine residues, 2 residues bind preferentially to the C and D sites. The chair form of N-acetylglucosamine may be able to bind to the D region. The saccharide residues of tetra-N-acetylglucosamine bind to the A-B-C-D sites, with the residues at the A-B-C sites having essentially the same conformation and orientation as those in the x-ray structure of tetra-N-acetylglucosamine-.delta.-lactone bound to lysozyme.