[Features of the interaction between alpha2-antiplasmin and plasminogen/plasmin].
The kinetic of plasmin, Va1442-plasmin, Lys530-plasmin inhibition reaction by alpha 2-antiplasmin as well as interaction of the inhibitor with different derivatives of the plasminogen and its fragments were studied. It was shown that plasmin, mini- and micro-plasmin activity decreased by 97, 88 and 85%, respectively, for equimolar ratio 1:1 of the inhibitor. The value of the inhibition reached its maximum in 1-2, 5-10 and 10-15 min, respectively. The constants of the complex formation rate were 1.4 x 10(6); 1.7 x 10(5) and 6.2 x 10(4) M-1s-1 for the plasmin, mini- and micro-plasmin with alpha 2-antiplasmin, respectively. Both 10(-2) M 6-aminohexanoic acid and 10(-1) M arginine reduced the complex formation rate between plasmin, mini-plasmin and alpha 2-antiplasmin to the value of the rate reaction between micro-plasmin and inhibitor. alpha 2-Antiplasmin bound with all investigated derivatives and fragments of plasminogen. The amount of inhibitor decreased in the series: plasmin, kringle 1-3, kringle 4, mini-plasminogen, micro-plasminogen. The kringle 1-4 and kringle 5 were determined to control the rate of reaction between enzyme and inhibitor, being not necessary for the inhibition. The comparison of the inhibitor interaction with DPP-plasmin, mini-plasminogen and micro-plasminogen displayed the possibility of the additional region existence in catalytic domain. This region participated in the complex with alpha 2-antiplasmin formation. It is supposed that the multisite interaction between plasmin and alpha 2-antiplasmin provides for the specificity and efficiency the inhibitor action.
Hrynenko
T V
TV
Palladin Institute of Biochemistry, NAS of Ukraine, Kyiv. grinenko@biochem.kiev.ua
Iusova
O I
OI
Zadorozhna
M B
MB
Makohonenko
Ie M
IeM
D015119:Aminocaproic Acid / Q000494:pharmacology; D001120:Arginine / Q000494:pharmacology; D001665:Binding Sites; D001667:Binding, Competitive; D005341:Fibrinolysin / Q000187:drug effects; D007700:Kinetics; D018082:Kringles / Q000187:drug effects; D010958:Plasminogen / Q000378:metabolism*; D011485:Protein Binding; D000979:alpha-2-Antiplasmin / Q000378:metabolism*; D000511:alpha-Macroglobulins / Q000187:drug effects
D000979:alpha-2-Antiplasmin; D000511:alpha-Macroglobulins; C024668:plasmin-alpha(2)-macroglobulin complex; D010958:Plasminogen; D001120:Arginine; D005341:Fibrinolysin; D015119:Aminocaproic Acid