[Role of lysine binding sites in activation of plasminogen by streptokinase]

Ukr Biokhim Zh (1999). 2003 Mar-Apr;75(2):25-32.
[Article in Russian]

Abstract

The function of lysine-binding sites in kringle domains K1-4 and K5 of plasminogen (Pg) during its activation by streptokinase (SK) was studied. Activation rates of Glu- and Lys-Pg exceed activation rate of mini- and micro-Pg 26 and 40 times, respectively. 6-Animohexanoic acid (6-AHA) in concentrations from 10(-5) to 10(-2) M inhibits activation of Glu-, Lys- and mini-Pg and does not impact the activation of micro-Pg. Complete inhibition of Lys-Pg activation occurs with presence of 10(-3) M 6-AHA while 90% inhibition of mini-Pg activation and 70% inhibition of Glu-Pg activation occur with 10(-2) M 6-AHA. Isolated kringles K1-3 and K4 of Pg inhibit activation of Glu-Pg by SK and concentrations [I]50 are 4.0 and 8.1 x 10(-6) M, respectively. Catalytic activity of Glu-Pg-SK, Lys-Pg-SK and Pm-SK complexes with respect to S 2251 is not inhibited by 6-AHA in concentrations from 10(-5) to 10(-2) M. Activation of substrate Pg by Pm-SK complex is also inhibited by 6-AHA in concentrations from 10(-5) to 10(-2) M; however, this effect of inhibition is significantly weaker than that with activation by SK. Cleavage of C-terminal Lys or chemical modification of NH2-groups of amino acid residues in SK molecule also results in the decrease of the Glu-Pg activation rate. Lysin-binding sites in K1-4 and K5 of Pg molecule are important at different steps of Pg activation process which includes formation of equimolar complex; structural reorganizations resulted in formation of active center in Pg; and binding of substrate Pg with Pg-SK complex. Lysin-binding sites in K1-4 of Pg are necessary for maintenance of high rate of Pg activation by SK.

Publication types

  • English Abstract

MeSH terms

  • Aminocaproic Acid / pharmacology
  • Antifibrinolytic Agents / pharmacology
  • Binding Sites
  • Catalysis
  • Dose-Response Relationship, Drug
  • Enzyme Activation
  • Fibrinolytic Agents / chemistry
  • Fibrinolytic Agents / metabolism
  • Fibrinolytic Agents / pharmacology*
  • Kinetics
  • Kringles
  • Lysine / metabolism*
  • Plasminogen / chemistry
  • Plasminogen / metabolism*
  • Streptokinase / chemistry
  • Streptokinase / metabolism
  • Streptokinase / pharmacology*
  • Substrate Specificity

Substances

  • Antifibrinolytic Agents
  • Fibrinolytic Agents
  • Plasminogen
  • Streptokinase
  • Lysine
  • Aminocaproic Acid