Lipscomb_1980_Proc.Natl.Acad.Sci.U.S.A_77_3875

The mode of binding of a ketonic substrate, which is an analogue of esters in which the O of the scissile bond is replaced by CH2, to carboxypeptidase A is similar to that of Gly-Tyr. The site is S'1, with the side chain in the pocket of the enzyme, the carboxylate salt-linked to Arg-145, and the carbonyl group bound to Zn. Thus, esters are probably cleaved at the peptide cleavage site, although not necessarily with the same rate-controlling step or by the same detailed mechanism. The large differences found between the behavior of the enzyme in solution and in one crystalline phase do not apply to a different crystalline phase.