Proteinase 3: substrate specificity and possible pathogenetic effect of Wegener's granulomatosis autoantibodies (c-ANCA) by dysregulation of the enzyme

Adv Exp Med Biol. 1993:336:55-60. doi: 10.1007/978-1-4757-9182-2_7.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Antibodies, Antineutrophil Cytoplasmic
  • Autoantibodies / pharmacology*
  • Elastin / metabolism
  • Granulomatosis with Polyangiitis / immunology*
  • Humans
  • Immunoglobulin G / pharmacology*
  • Molecular Sequence Data
  • Myeloblastin
  • Peptides / chemistry
  • Peptides / metabolism
  • Serine Endopeptidases / immunology
  • Serine Endopeptidases / metabolism*
  • Substrate Specificity
  • alpha 1-Antitrypsin / pharmacology

Substances

  • Antibodies, Antineutrophil Cytoplasmic
  • Autoantibodies
  • Immunoglobulin G
  • Peptides
  • alpha 1-Antitrypsin
  • Elastin
  • Serine Endopeptidases
  • Myeloblastin