Substrate and inhibitor studies on proteinase 3

FEBS Lett. 1992 Feb 3;297(1-2):119-23. doi: 10.1016/0014-5793(92)80340-m.

Abstract

Various amino acid and peptide thioesters were tested as substrates for human proteinase 3 and the best substrate is Boc-Ala-Ala-Nva-SBzl with a kcat/Km value of 1.0 x 10(6) M-1.s-1. Boc-Ala-Ala-AA-SBzl (AA = Val, Ala, or Met) are also good substrates with kcat/Km values of (1-4) x 10(5) M-1.s-1. Substituted isocoumarins are potent inhibitors of proteinase 3 and the best inhibitors are 7-amino-4-chloro-3-(2-bromoethoxy)isocoumarin and 3,4-dichloroisocoumarin (DCI) with kobs/[I] values of 4700 and 2600 M-1.s-1, respectively. Substituted isocoumarins, peptide phosphonates and chloromethyl ketones inhibited proteinase 3 less potently than human neutrophil elastase (HNE) by 1-2 orders of magnitude.

Publication types

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

MeSH terms

  • Amino Acid Chloromethyl Ketones / pharmacology
  • Autoradiography
  • Coumarins / pharmacology
  • Electrophoresis, Polyacrylamide Gel
  • Humans
  • Hydrolysis
  • Kinetics
  • Myeloblastin
  • Organophosphorus Compounds / pharmacology
  • Protease Inhibitors*
  • Serine Endopeptidases / metabolism*
  • Substrate Specificity

Substances

  • Amino Acid Chloromethyl Ketones
  • Coumarins
  • Organophosphorus Compounds
  • Protease Inhibitors
  • Serine Endopeptidases
  • Myeloblastin