Structure of a Specific Acyl-Enzyme Complex formed between ß-Casomorphin-7 and Porcine Pancreatic Elastase

RC Wilmouth, IJ Clifton, CV Robinson, PL Roach, RT Aplin, Nicholas James Westwood, J Hajdu, CJ Schofield

Research output: Other contribution

65 Citations (Scopus)

Abstract

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 Angstrom 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 Burgi-Dunitz trajectory.

Original languageEnglish
Volume4
Publication statusPublished - Jun 1997

Keywords

  • ELECTROSPRAY MASS-SPECTROMETRY
  • CATALYTIC WATER MOLECULE
  • GAMMA-CHYMOTRYPSIN
  • SUBSTRATE-SPECIFICITY
  • ALPHA-CHYMOTRYPSIN
  • SERINE PROTEASES
  • HUMAN-LEUKOCYTE
  • MECHANISM
  • INTERMEDIATE
  • INHIBITORS

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