Abstract
We analyzed the correlation between the conformational strain and the binding kinetics in antigen-antibody interactions. The catalytic antibodies 6D9, 9C10, and 7C8 catalyze the hydrolysis of a nonbioactive chloramphenicol monoester derivative to generate a bioactive chloramphenicol. The crystal structure of 6D9 complexed with a transition-state analog (TSA) suggests that 6D9 binds the substrate to change the conformation of the ester moiety to a thermodynamically unstable twisted conformation, enabling the substrate to reach the transition state during catalysis. The present binding kinetic analysis showed that the association rate for 6D9 binding to the substrate was much lower than that to TSA, whereas those for 9C10 and 7C8 binding were similar to those to TSA. Considering that 7C8 binds to the substrate with little conformational change in the substrate, the slow association rate observed in 6D9 could be attributed to the conformational strain in the substrate.