Dual effect of synthetic plasmin substrates on plasminogen activation

K. Kolev, Whyte G. Owen, R. Machovich

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

The effect of plasmin substrates d-valyl-l-leucyl-lysine-p-nitroanilide (S-2251) and H-d-norleucyl-hexahydrotyrosyl-lysine-p-nitroanilide (Spectrozyme-PL) on the rate of activation of native human plasminogen in physiological salt solution is studied. Plasminogen activation by two-chain urokinasa-type plasminogen activator (urokinase), two-chain tissue-type plasminogen activator (tc-tPA) or trypsin, but not by single chain tPA (sc-tPA) is increased 5- to 10-fold by both substrates, as determined by electrophoretic and spectrophotometric kinetic analysis. The amidolytic activity of sc-tPA, on the other hand, is inhibited by the plasmin substrates in a non-competitive manner (KI of 6.4 · 10-4 M for S-2251 and 2.9 · 10-4 M for Spectrozyme-PL), whereas urokinase and tc-tPA activities are not affected. It is concluded that plasmin substrates containing a lysine residue have a general capacity to enhance plasminogen activation presumably by inducing a conformational change in the native zymogen in a manner similar to 6-aminohexanoate, while the same substrates are inhibitory both on the amidolytic activity of sc-tPA and the activation of native and des1-77-plasminogen by sc-tPA.

Original languageEnglish
Pages (from-to)239-245
Number of pages7
JournalBiochimica et Biophysica Acta (BBA)/Protein Structure and Molecular
Volume1247
Issue number2
DOIs
Publication statusPublished - Mar 15 1995

Fingerprint

Plasminogen
Fibrinolysin
valyl-leucyl-lysine 4-nitroanilide
Chemical activation
Urokinase-Type Plasminogen Activator
Tissue Plasminogen Activator
Substrates
Lysine
Aminocaproates
Enzyme Precursors
Population Groups
Trypsin
Salts
Kinetics
H-norleucyl-hexahydrotyrosyl-lysine-4-nitroanilide

Keywords

  • Plasmin substrate S-2251
  • Plasminogen
  • Spectrozyme PL
  • Tissue plasminogen activator
  • Urokinase

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology
  • Structural Biology

Cite this

Dual effect of synthetic plasmin substrates on plasminogen activation. / Kolev, K.; Owen, Whyte G.; Machovich, R.

In: Biochimica et Biophysica Acta (BBA)/Protein Structure and Molecular, Vol. 1247, No. 2, 15.03.1995, p. 239-245.

Research output: Contribution to journalArticle

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