26-10 FAB-DIGOXIN COMPLEX - AFFINITY AND SPECIFICITY DUE TO SURFACE COMPLEMENTARITY

We have determined the three-dimensional structures of the antigen-bin ding fragment of the anti-digoxin monoclonal antibody 26-10 in the unc omplexed state at 2.7 angstrom resolution and as a complex with digoxi n at 2.5 angstrom resolution. Neither the antibody nor digoxin undergo es any significant conformational changes upon forming the complex. Di goxin interacts primarily with the antibody heavy chain and is oriente d such that the carbohydrate groups are exposed to solvent and the lac tone ring is buried in a deep pocket at the bottom of the combining si te. Despite extensive interactions between antibody and antigen, no hy drogen bonds or salt links are formed between 26-10 and digoxin. Thus the 26-10-digoxin complex is unique among the known three-dimensional structures of antibody-antigen complexes in that specificity and high affinity arise primarily from shape complementarity.