MOLECULAR MODELING STUDIES OF LYSOZYME CATALYZED-HYDROLYSIS OF SYNTHETIC SUBSTRATES

Kinetic data for the lysozyme catalysed hydrolysis of aryl chitooligos ides were surveyed. Both electron-donating and electron-withdrawing su bstituents on the departing aryl aglycones enhance the rate of hydroly ses. The parallel pH-rate profiles implicate that identical catalytic residues are involved in the hydrolytic fission of the glycosyl-arylox y bond of these two groups of synthetic substrates, Molecular modellin g studies of lysozyme complexes with aryl diN-acetyl chitobiosides and their intermediates were performed. The two synthetic substrates bear ing aryl aglycones with opposite electronic effects bind to the active site of lysozyme in different conformations. Based on the energetic a nd geometric considerations, the oxocarbonium ion whose pyranose ring D in a sofa conformation is the most plausible reaction intermediate f or the lysozyme catalysed hydrolysis of the synthetic substrates. The modelling study also suggests that considerable conformational changes of both the lysozyme binding site and the chitobiosyl group accompany the formation of the glycosyl enzyme intermediate, In particular, the chitobiosyl group undergoes a dislocation of the pyranose ring C from the subsite C and a constraint of the pyranose ring D to form a boat conformer. (C) 1997 Elsevier Science Ltd.