PROLYL OLIGOPEPTIDASE - AN UNUSUAL BETA-PROPELLER DOMAIN REGULATES PROTEOLYSIS

Prolyl oligopeptidase is a large cytosolic enzyme that belongs to a ne w class of serine peptidases. The enzyme is involved in the maturation and degradation of peptide hormones and neuropeptides, which relate t o the induction of amnesia. The 1.4 Angstrom resolution crystal struct ure is presented here. The enzyme contains a peptidase domain with an alpha/beta hydrolase fold, and its catalytic triad (Ser554, His680, As p641) is covered by. the central tunnel of an unusual beta propeller. This domain makes prolyl oligopeptidase an oligopeptidase by excluding large structured peptides from the active. site. In this way, the pro peller protects larger peptides and proteins from proteolysis in the c ytosol. The structure is also obtained with a transition state inhibit or, which may facilitate drug design to treat memory disorders.