ANATOMY OF AN ANTIBODY MOLECULE - STRUCTURE, KINETICS, THERMODYNAMICSAND MUTATIONAL STUDIES OF THE ANTILYSOZYME ANTIBODY D1.3

Using site-directed mutagenesis, x-ray crystallography, microcalorimet ric, equilibrium sedimentation and surface plasmon resonance detection techniques, we have examined the structure of an antibody-antigen com plex and the structural and thermodynamic consequences of removing spe cific hydrogen bonds and van der Waals interactions in the antibody-an tigen interface. These observations show that the complex is considera bly tolerant, both structurally and thermodynamically, to the truncati on of antibody and antigen side chains that form contacts. Alterations in interface solvent structure for two of the mutant complexes appear to compensate for the unfavorable enthalpy changes when antibody-anti gen interactions are removed. These changes in solvent structure, alon g with the increased mobility of side chains near the mutation site, p robably contribute to the observed entropy compensation. In concert, d ata from structural studies, reaction rates, calorimetric measurements and site-directed mutations are beginning to detail the nature of ant ibody-protein antigen interactions.