The hinge-bending mode in lysozyme

Abstract

A COMPLETE description of an enzyme requires a knowledge of its structure and the dynamics of its function. From the crystal structures of enzymes and enzyme–inhibitor complexes and the known chemistry of model systems, it has been possible in some cases to draw reasonable inferences concerning the mechanisms of enzyme-catalysed reactions. Little has been done so far, however, to supplement such essentially static results by an investigation of the reaction dynamics. This requires an understanding of the internal motions of the enzyme, as well as those of the substrate, since both are likely to be essential to the function. Here we present a theoretical study of a low frequency vibration involving the two globular lobes of lysozyme between which the cleft containing the active site is located¹. Any motion involving this cleft could play a part in the catalytic activity; in fact, atom displacements of up to 0.75 Å found in a comparison of the free enzyme and the enzyme-inhibitor complex indicate that the cleft has closed down in the latter². The force constant for the low frequency bending vibration corresponding to the opening and closing of the cleft is obtained from empirical energy functions³. Because the protein surface moves appreciably during the vibration, damping effects resulting from the viscous dissipation in the solvent are included in the calculation^4,5.