STRUCTURE OF AN ANTIBODY LYSOZYME COMPLEX UNEXPECTED EFFECT OF A CONSERVATIVE MUTATION

The structure of the complex between the Fab HyHEL-5 and chicken lysoz yme revealed a large interface region containing 23 lysozyme and 28 Fa b residues. Arg68 of the lysozyme is centrally placed in this interfac e and theoretical studies together with binding assays of this Fab to different avian lysozymes have previously shown that this arginine res idue is an important contributor to the binding. The Arg68-->Lys mutan t binds 10(3) times less well to the HyHEL-5 Fab. We have examined the refined crystal structure of the complex of this mutant lysozyme with the Fab. No global changes occur, but. there is an introduction of a new water molecule into the interface that mediates the hydrogen bondi ng interactions between the lysine and residues on the Fab. These data are compared with the effects of similar changes on the inhibition of serine proteases such as trypsin where the energetic effects of this substitution are small.