Structure of a specific acyl-enzyme complex formed between beta-casomorphin-7 and porcine pancreatic elastase.

Journal article

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.

Authors: Wilmouth, R; Clifton, I; Robinson, C; Roach, P; Aplin, RT

• Publication status: Published
• Journal: Nature structural biology
• Volume: 4
• Issue: 6
• Pages: 456-462
• Publication date: 1997-06-01
• DOI: 10.1038/nsb0697-456
• ISSN: 1072-8368
• Language: English
• Keywords: Kinetics; Swine; Crystallography, X-Ray; Peptides; Endorphins; Humans; Pancreatic Elastase; Models, Molecular; Animals; Peptide Fragments; Substrate Specificity; Protein Conformation; Mass Spectrometry