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Substrate and inhibitor studies on proteinase 3
Author(s) -
Kam Chih-Min,
Kerrigan John E.,
Dolman Koert M.,
Goldschmeding Roel,
Von dem Borne Albert E.G.Kr.,
Powers James C.
Publication year - 1992
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(92)80340-m
Subject(s) - isocoumarins , enzyme kinetics , elastase , peptide , isocoumarin , chemistry , substrate (aquarium) , stereochemistry , proteinase 3 , enzyme , amino acid , biochemistry , active site , biology , catalysis , myeloperoxidase , ecology , immunology , inflammation
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 k cal / K m value of 1.0 × 10 6 nM it‐1 s it‐1 Boc‐Ala‐Ala‐AA‐SBzl (AA = Val, Ala, or Met) are also good substrates with k cal / K m values of (1‐4) × 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 k obs /[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.