Structures of esterase-like catalytic antibodies

We report structures of complexes of two esterase-like catalytic antibodies elicited against phosphonate transition-state analogues (TSAs) of the reac tion their catalyse; the complexes studied are with these TSAs and species along the reaction pathway. The TSAs are deeply sequestered in a pocket loc ated in the combining site at the interface of the tare antibody polypeptid e chains; the deepest part of this pocket is almost completely hydrophobic. The larger number and stronger hydrogen bonds between the antibodies and t he TSAs as compared to those established with the corresponding substrates account for the catalytic activity; transition state stabilisation is throu gh oxyanion holes elicited in response to the negatively charged phosphonat e oxygens.