[Modifying effect of antiplasminogen monoclonal antibody IV-1c on human plasmin catalytic properties]

Ukr Biokhim Zh (1999). 2002 Jul-Aug;74(4):61-70.
[Article in Russian]

Abstract

Antiplasminogen monoclonal antibody IV-1c (IV-1c) binds to Val 709-Gly 718 site of plasminogen (Pg) protease domain, which is far removed from the active site. Pg-IV-1c complex formation induces catalytic activity in proenzymes active site. Influence of IV-1c binding to plasmin (Pm) on Pm catalytic properties has not been investigated yet. Data on catalytic properties of Pm in equimolar Pm-IV-1c complex are presented. It was found that Pm and mini-Pm amidolytic and caseinolytic activity was twice as high as in Pm-IV-1c and mini-Pm-IV-1c complexes. 20 mM 6-AHA and 100 mM arginine did not influence this rise. The increase of amidolytic activity is connected with reduction of K(m) of S 2251 hydrolysis reaction for Pm and mini-Pm from 0.125 and 0.43 to 0.05 and 0.23 mM, correspondingly. Kcat remains almost the same. Fibrinolytic and fibrinogenolytic activity of Pm in Pm-IV-1c complex decreased to 20% of initial value alpha 2-Antiplasmin inhibited Pm activity in complex Pm-IV-1c by 80%. Pm-IV-1c complex did not activate free Pg, but activated equimolar Pg-IV-1c complex. Affinity of IV-1c to Pm and Pg was the same as C50 approximately 1.5 nM. Binding of Pm with IV-1c in a complex: a) leads to increase of Pm active site affinity to LMW substrates; b) causes steric hindrances for fibrin/fibrinogen access to Pm active site; c) proceeds with the same affinity for Pm and Pg, that indicates to invariable Val 709-Gly 718 site conformation after Pg transition in Pm.

Publication types

  • English Abstract

MeSH terms

  • Aminocaproic Acid / pharmacology
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / immunology*
  • Catalysis
  • Humans
  • Plasminogen / chemistry
  • Plasminogen / immunology
  • Plasminogen / metabolism*
  • Streptokinase / metabolism*
  • alpha-2-Antiplasmin / pharmacology

Substances

  • Antibodies, Monoclonal
  • alpha-2-Antiplasmin
  • Plasminogen
  • Streptokinase
  • Aminocaproic Acid