Effects of Various N-Terminal Peptides of Glu-Plasminogen on Keeping Its Tight Conformation of Glu-Plasminogen

Abstract

Glu-plasminogen (Glu-plg) is a single chain plasma glycoprotein, which is the zymogen form of a serine protease, plasmin. The conversion from the precursor to the enzyme occurs as a result of cleavage of the Arg⁵⁶⁰-Val⁵⁶¹ peptide bond in plasminogen splitting to the heavy chain and the light chain, by several activators, which include tissue type plasminogen activator (tPA), urokinase type plasminogen activator (uPA) and streptokinase [1]. In heavy chain of plasmin which coincides with the sequence of Glu¹-Arg⁴⁵⁰ of Glu-plg, there are five conformationaly similar loop domains called kringle domain which binds to many regulatory molecules like fibrin and lysine analogues. Glu-plg possesses a tight conformation in the presence of chloride ion and absence of lysine analogues, and is hardly activated by activators, whereas Lys-plasminogen (Lys-plg), which is generated by the cleavage of Lys⁷⁶-Lys⁷⁷ peptide bond of Glu-plg by plasmin, has a looser conformation and is readily activatable [2~9]. The tight conformation of Glu-plg is considered to be caused by the intramolecular binding of N-terminal portion to the kringle 1 [10, 11] or the kringle 4 domain [12] through lysine binding site (LBS) or kringle 5 domain through amino-hexyl (AH) site [13] on the same molecule. Lysine analogues, therefore, could alter the conformation of Glu-plg to the looser form [3, 6, 8, 14] by dissociating the N-terminal peptides from LBS or AH site.