title: Covalent structure of two novel neutrophile leucocyte-derived proteins of porcine and human origin. Neutrophile elastase homologues with strong monocyte and fibroblast chemotactic activities.
abstract: The covalent structures of two, novel, neutrophile, leucocyte-derived, strongly basic proteins of porcine and human origin have been determined by microsequencing in combination with time-of-flight plasma desorption mass spectrometry. The porcine protein primary structure of 219 amino acid residues was shown to contain 6 cysteine residues, 2 putative carbohydrate sites and 14% basic residues. The human protein contained 221 amino acid residues of which 8 were cysteine, 4 putative carbohydrate sites and 12% basic. A 47% direct sequence similarity to human neutrophile elastase was found, but due to mutations of two of the three amino acids in the catalytic triad, proteolytic activity is absent. Modelling and alignment studies unveil a close relationship of both proteins to the serine protease family, the greatest similarity being to those serine proteases present in granules from peripheral blood cells. Both proteins have been shown to be chemotactically active for monocytes and fibroblasts in vitro.
authors.affiliation: Novo Nordisk A/S, Copenhagen, Denmark.
authors.forename: H
authors.initials: H
authors.lastname: Flodgaard
authors.forename: E
authors.initials: E
authors.lastname: Ostergaard
authors.forename: S
authors.initials: S
authors.lastname: Bayne
authors.forename: A
authors.initials: A
authors.lastname: Svendsen
authors.forename: J
authors.initials: J
authors.lastname: Thomsen
authors.forename: M
authors.initials: M
authors.lastname: Engels
authors.forename: A
authors.initials: A
authors.lastname: Wollmer
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D001798:Blood Proteins / Q000235:genetics*; D002634:Chemotaxis, Leukocyte; D002851:Chromatography, High Pressure Liquid; D005347:Fibroblasts / Q000276:immunology; D006493:Heparin / Q000378:metabolism; D006801:Humans; D019272:Leukocyte Elastase; D007962:Leukocytes / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009000:Monocytes / Q000276:immunology; D009504:Neutrophils / Q000378:metabolism*; D010196:Pancreatic Elastase / Q000235:genetics*; D016415:Sequence Alignment; D012697:Serine Endopeptidases / Q000235:genetics; D013552:Swine; D014357:Trypsin
chemical_list: D000596:Amino Acids; D001798:Blood Proteins; D006493:Heparin; D012697:Serine Endopeptidases; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase; D014357:Trypsin