title: Structure of a specific acyl-enzyme complex formed between beta-casomorphin-7 and porcine pancreatic elastase.
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 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.affiliation: Oxford Centre for Molecular Sciences, UK.
authors.forename: R C
authors.initials: RC
authors.lastname: Wilmouth
authors.forename: I J
authors.initials: IJ
authors.lastname: Clifton
authors.forename: C V
authors.initials: CV
authors.lastname: Robinson
authors.forename: P L
authors.initials: PL
authors.lastname: Roach
authors.forename: R T
authors.initials: RT
authors.lastname: Aplin
authors.forename: N J
authors.initials: NJ
authors.lastname: Westwood
authors.forename: J
authors.initials: J
authors.lastname: Hajdu
authors.forename: C J
authors.initials: CJ
authors.lastname: Schofield
mesh_terms: D000818:Animals; D018360:Crystallography, X-Ray; D004723:Endorphins / Q000737:chemistry* / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D007700:Kinetics; D013058:Mass Spectrometry / Q000379:methods; D008958:Models, Molecular; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism* / Q000502:physiology; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D013379:Substrate Specificity; D013552:Swine
chemical_list: D004723:Endorphins; D010446:Peptide Fragments; D010455:Peptides; C041128:beta-casomorphin 7; D010196:Pancreatic Elastase