The structure of aspartyl dipeptidase reveals a unique fold with a Ser-His-Glu catalytic triad

The three-dimensional structure of Salmonella typhimurium aspartyl dipeptid ase, peptidase E, was solved crystallographically and refined to 1.2-Angstr om resolution. The structure of this 25-kDa enzyme consists of two mixed be ta -sheets forming a V, flanked by six alpha -helices. The active site cont ains a Ser-His-Glu catalytic triad and is the first example of a serine pep tidase/protease with a glutamate in the catalytic triad. The active site Se r is located on a strand-helix motif reminiscent of that found in alpha/bet a -hydrolases. but the polypeptide fold and the organization of the catalyt ic triad differ from those of the known serine proteases. This enzyme is a member of a family of serine hydrolases and appears to represent a new exam ple of convergent evolution of peptidase activity.