On the nature of antibody combining sites: Unusual structural features that may confer on these sites an enhanced capacity for binding ligands

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Abstract
A detailed analysis of the structural aspects of antibody–antigen interactions has been made possible by the availability of X‐ray structures for three complexes of antilysozyme Fabs to lysozyme (reviewed by Davies et al: J. Biol. Chem. 263:10541–10544, 1988.) Examination of the antigen‐contacting residues in the three antilysozyme Fabs reveals the occurrence of a large number of aromatics, particularly tyrosines, and the absence of apolar, aliphatic residues. Calculation of the frequency of occurrence of the various amino acids types reveals that tyrosines are three times, and histidines and asparagines eight times, more likely to be found in the complementarity‐determinig regions that in the framework of the variability of the residue in FVs (the modules containing variable domains of the light and heavy chains) of known three‐dimensional structure indicates that tryosines and tryptophans are more exposed when they occur in the complementarity‐determining regions that when in the framework. Furthermore, many more of the asparagines in the complementarity‐determining regions than in the framework are buried. These aspararagines appear to have a structural role in that they hydrogen bond through their side chains to other side chains and, Even more so, to the protein backbone. The stabilizing effect of the asparragines, plus the rigidity of the framework, may serve to allow the greater exposure of the aromatic residues to solvent. In view of the greater potential contribution of aromatic side chains to the total binding energy, these results suggest that antibody‐combining sites have structural features that make them especially studied for interacting with lagands.

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