title: Proteinase 3: substrate specificity and possible pathogenetic effect of Wegener's granulomatosis autoantibodies (c-ANCA) by dysregulation of the enzyme.
abstract: Reactivity of proteinase 3 (PR3) was tested against various amino acid and thioester substrates. The best substrate is Boc-Ala-Ala-Nva-SBzl with a kcat/Km value of 1.0 x 10(6) M-1.s-1. We also studied the effect of C-ANCA on PR3 proteolytic activity towards elastin and inactivation by alpha 1-antitrypsin (alpha 1AT). C-ANCA IgG from 8 patients with active Wegener's granulomatosis were tested and found to inhibit elastin degradation by PR3 and to prevent the inactivation of PR3 by alpha 1AT.
authors.affiliation: Central Laboratory of The Netherlands, Red Cross Blood Transfusion Service, Amsterdam.
authors.forename: K M
authors.initials: KM
authors.lastname: Dolman
authors.forename: B A
authors.initials: BA
authors.lastname: van de Wiel
authors.forename: C M
authors.initials: CM
authors.lastname: Kam
authors.forename: J E
authors.initials: JE
authors.lastname: Kerrigan
authors.forename: C E
authors.initials: CE
authors.lastname: Hack
authors.forename: A E
authors.initials: AE
authors.lastname: von dem Borne
authors.forename: J C
authors.initials: JC
authors.lastname: Powers
authors.forename: R
authors.initials: R
authors.lastname: Goldschmeding
mesh_terms: D000595:Amino Acid Sequence; D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies / Q000494:pharmacology*; D004549:Elastin / Q000378:metabolism; D014890:Granulomatosis with Polyangiitis / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology*; D008969:Molecular Sequence Data; D053146:Myeloblastin; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D012697:Serine Endopeptidases / Q000276:immunology / Q000378:metabolism*; D013379:Substrate Specificity; D000515:alpha 1-Antitrypsin / Q000494:pharmacology
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies; D007074:Immunoglobulin G; D010455:Peptides; D000515:alpha 1-Antitrypsin; D004549:Elastin; D012697:Serine Endopeptidases; D053146:Myeloblastin