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首页> 外文期刊>Biochemistry >Thermodynamic Characteristics of Plasminogen Activation by Indirect Activators
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Thermodynamic Characteristics of Plasminogen Activation by Indirect Activators

机译：间接活化剂活化纤溶酶原的热力学特征

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Several indirect plasminogen (Pg) activators are known including streptokinase and the monoclonal antibody IV-Ic,whose mechanism of activation is well studied.To characterize thermodynamically the activation of Pg by streptokinase (SK) and the monoclonal antibody (mAB) FV-Ic,the activation energies were calculated for various reaction stages.Activation energy of 7.4 kcal/mol was determined forthe interaction of the chromogenic substrate S-2251 with plasmin (Pm) and activated equimolar complexes Pm-SK and Pg*SK at the steady-state reaction stage,and 18.7 kcal/mol with the complexes Pg*IV-Ic.A 2.5-fold increase in the energy of activation for the Pg*IV-Ic complex suggests a more intricate mechanism of its interaction with the substrate.At the stage of increasing active center concentrations and the formation of activated complexes Pg*SK and Pg*mAB IV-Ic,the activation energy was found to be 10.5 and 38 kcal/mol,respectively.At this reaction stage the conformational rearrangement of Pg molecule with the formation of active center is the limiting stage determining the reaction rate.Unexpectedly high energy of activation at the second stage of interaction between mAB IV-Ic and Pg suggests several simultaneous reactions and complexity of conformation rearrangement in the Pg molecule in activated complexes,thus requiring large energy expense.Formation of the active center is probably accompanied by its transition within a narrow temperature range into another conformation state with the change in activation parameters of the reaction.Quantitative evaluation of the studied reactions from the perspective of thermodynamics of the enzymatic reactions gives more comprehensive characteristics of the activation mechanism.
机译：已知有几种间接的纤溶酶原（Pg）激活剂，包括链激酶和单克隆抗体IV-Ic，其激活机理已得到很好的研究。为表征链激酶（SK）和单克隆抗体（mAB）FV-Ic对Pg的激活进行热力学表征，稳态反应下生色底物S-2251与纤溶酶（Pm）以及活化的等摩尔配合物Pm-SK和Pg * SK的相互作用确定为7.4 kcal / mol的活化能。 Pg * IV-Ic配合物的活化能增加了2.5倍，表明Pg * IV-Ic配合物的活化能提高了2.5倍，表明其与底物相互作用的机理更加复杂。增加活性中心浓度并形成活化的复合物Pg * SK和Pg * mAB IV-Ic，其活化能分别为10.5和38 kcal / mol。在此反应阶段，Pg mo的构象重排具有活性中心形成的大分子是决定反应速率的极限阶段.mAB IV-Ic与Pg相互作用的第二阶段出乎意料的高活化能表明活化的复合物中Pg分子同时发生多个反应和构象重排的复杂性，因此需要大量的能源消耗。随着反应活化参数的变化，活性中心的形成可能伴随着它在狭窄的温度范围内转变为另一种构象状态。从反应热力学的角度对所研究的反应进行定量评估。酶促反应提供了更全面的激活机制特征。

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