STRUCTURE OF A SPECIFIC ACYL-ENZYME COMPLEX FORMED BETWEEN BETA-CASOMORPHIN-7 AND PORCINE PANCREATIC ELASTASE

Mass spectrometric screening reveals that an unmodified natural heptap eptide-human beta-casomorphin-7, an internal sequence of human beta-ca sein that possesses opioid-like activity-reacts with porcine pancreati c elastase to form an unusually stable acyl-enzyme complex at low pH. X-ray crystallographic analysis (to 1.9 Angstrom resolution) at pH 5 s hows continuous electron density linking the C-terminal isoleucine of beta-casomorphin-7 to Ser 195 through an ester bond. The structure rev eals a well defined water molecule (Wat 317), equidistant between the carbon of the ester carbonyl and N epsilon 2 of His 57. Deprotonation of Wat 317 will produce a hydroxide ion positioned to attack the ester carbonyl through the favoured Burgi-Dunitz trajectory.