纤溶酶原的构象变化：谷氨酸纤溶酶原N端肽段的作用

Conformational change of plasminogen: effects of N-terminal peptides of Glu-plasminogen.

作者信息

Takada Y, Urano T, Takada A

机构信息

Department of Physiology, Hamamatsu University, School of Medicine, Shizuoka-ken, Japan.

出版信息

Thromb Res. 1993 Apr 15;70(2):151-9. doi: 10.1016/0049-3848(93)90156-i.

DOI:10.1016/0049-3848(93)90156-i

PMID:8391730

Abstract

Seven peptides were synthesized to analyze the mechanism of the intramolecular binding of the N-terminal peptide of Glu-plasminogen (Glu-plg) to its kringles. They were Ala44-Lys50, Ala44-Glu51, Ala44-Ser49, Val17-Gly23, Lys19-Gly23, Lys19-Gln21 and Lys19-Lys20. Ala44-Lys50, Ala44-Glu51 and Lys19-Lys20.enhanced the activation of Glu-plg by tissue plasminogen activator (t-PA) or urinary plasminogen activator (u-PA). The activation of Lys-plg, however, was not influenced by these peptides. Therefore, it is suggested that these three peptides worked on Glu-plg in a similar manner as lysine analogue by making the conformation of Glu-plg looser. These peptides did not have any direct effects on u-PA and t-PA. Concerning the effect on fibrinolysis Ala44-Lys50 and Lys19-Lys20 prolonged euglobulin clot lysis time. These results indicate that Ala44-Glu51 may be a responsible binding site in the N-terminal portion of Glu-plg, and LBS of kringle 1 or 4 is the binding site of N-terminal portion of Glu-plg.

摘要

合成了七种肽，以分析谷氨酸纤溶酶原（Glu-plg）的N端肽与其kringle结构域分子内结合的机制。它们分别是Ala44-Lys50、Ala44-Glu51、Ala44-Ser49、Val17-Gly23、Lys19-Gly23、Lys19-Gln21和Lys19-Lys20。Ala44-Lys50、Ala44-Glu51和Lys19-Lys20增强了组织纤溶酶原激活剂（t-PA）或尿纤溶酶原激活剂（u-PA）对Glu-plg的激活作用。然而，这些肽对赖氨酸纤溶酶原（Lys-plg）的激活没有影响。因此，推测这三种肽通过使Glu-plg的构象更松散，以与赖氨酸类似物相似的方式作用于Glu-plg。这些肽对u-PA和t-PA没有任何直接影响。关于对纤维蛋白溶解的影响，Ala44-Lys50和Lys19-Lys20延长了优球蛋白凝块溶解时间。这些结果表明，Ala44-Glu51可能是Glu-plg N端部分的一个关键结合位点，kringle 1或4的赖氨酸结合位点（LBS）是Glu-plg N端部分的结合位点。