Схема учитывает возможность наличия промежуточных активаторных комплексов и существование положительной обратной связи.
Ключевые слова: сериновые протеиназы, активация плазминогена, плазмин, моноклональное антитело, каталитическая активность.
Slominsky A. Yu. The induction of plasminogen catalytic activity by monoclonal antibody IV-1c. - Manuscript.
Thesis for the scientific degree of candidate of biological sciences, by speciality 03.00.04 - biochemistry. Palladin Institute of Biochemistry of National Academy of Sciences of Ukraine, Kyiv, 2003.
The mechanisms of induction of plasminogen catalytic activity were studied by antiplasminogen monoclonal antibody IV-1c (mAb IV-1c). The complex plasminogen–mAb IV-1c was shown to be a good model for the studying of the mechanism of indirect plasminogen activation. The influence of some factors (temperature, ionic strength, pH, divalent cations, anions) on the process of catalytic activity induction was studied. The stability of the antigen-antibody complex and the main parameters of the induction process were determined. The dependence of the induction rate on proton concentration in the medium have been demonstrated. It was shown the necessity of the conversion of Glu-plasminogen to Lys-like conformation of plasminogen during lag-period of the induction process. The dependence of this process on divalent cations was shown. Owing to the activation energy data the existence of significant conformation changes of plasminogen-mAb IV-1c complex, before catalytic activity induction were demonstrated. The inhibition of the catalytic activity of plasminogen-mAb IV-1c complex by a2-antiplasmin was demonstrated, and existence of catalytic Ser-His-Asp triade at the beginning of the second (fast) reaction phase was shown. The results of the studies of the catalytic activity induction mechanisms let us to suggest the scheme of reaction which may be general for nonproteolytic activation. This scheme includes the several successive reactions, such as: the formation of antigen-antibody complex, the conversion of Glu-plasminogen to Lys-like form, the interaction of lysine-binding site with C-terminal Lys of monoclonal antibody g-chain and plasmin active site exposition. The scheme takes into account possibility of intermediate activator complexes and positive feed-back existance.
Key words: serine proteinase, plasminogen activation, plasmin, monoclonal antibody, catalytic activity.