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Mass spectrometric screening reveals that an unmodified natural heptapeptide--human beta-casomorphin-7, an internal sequence of human beta-casein that possesses opioid-like activity--reacts with porcine pancreatic elastase to form an unusually stable acyl-enzyme complex at low pH. X-ray crystallographic analysis (to 1.9 A resolution) at pH 5 shows continuous electron density linking the C-terminal isoleucine of beta-casomorphin-7 to Ser 195 through an ester bond. The structure reveals 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 Bürgi-Dunitz trajectory.


Journal article


Nat Struct Biol

Publication Date





456 - 462


Animals, Crystallography, X-Ray, Endorphins, Humans, Kinetics, Mass Spectrometry, Models, Molecular, Pancreatic Elastase, Peptide Fragments, Peptides, Protein Conformation, Substrate Specificity, Swine