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J. Biochem, 1998, Vol. 123, No. 1 71-77
© 1998 Japanese Biochemical Society

research-article

Role of the Kringle Domain in Plasminogen Activation with Staphylokinase1

Koichi Arai*, Seiji Madoiwa*, Jun Mimuro*, Shinji Asakura*, Michio Matsuda*, Tomoyuki Sako{dagger} and Yoichi Sakata*,2

*Division of Hemostasis and Thrombosis, Institute of Hematology, Jichi Medical School, Minamikawachi-machi Tochigi 329-04
{dagger}Yakult Central Institute for Microbiological Research Kunitachi, Tokyo 186

2To whom correspondence should be addressed.

We have evaluated the effect of lysine binding sites in krigle structures on the activation of plasminogen with plasmin and staphylokinase (SAK) complex and on the binding of plasminogen to SAK. Activation of native plasminogen (Glu-plasminogen) by a catalytic amount of plasmin-SAK complex increased in the presence of {varepsilon}-amino-n-caproic acid (EACA) and then decreased with higher concentrations of EACA. By contrast, activation of modified plasminogen (Lys-plasminogen) decreased in an EACA-concentration-dependent manner. This decrease was explained by a more than 10-fold higher Km for activation of Lys-plasminogen with a catalytic amount of plasmin-SAK complex in the presence of EACA. EACA was a competitive inhibitor with K1 0.23 mM. In addition, the Km for activation of mini-plasminogen, which lacks first four kringle structures (K1+2+3+4), was at least 3.5-fold higher than that for the activation of Lys-plasminogen. Furthermore, EACA showed a negligible inhibitory effect on the activation of mini-plasminogen by the plasmin-SAK complex. We observed a similar biphasic effect of EACA on the binding of Glu-plasminogen to SAK and a dose-dependent effect on the Lys-plasminogen binding to SAK by gel filtration methods. Since EACA binds to plasminogen via lysine binding sites in the kringle structure, we propose that the lysine binding site in K1+2+3+4 domain plays a role in the activation of plasminogen by plasmin-SAK complex, and in the binding of plasminogen to SAK.

1This work was partially supported by a Grant-in-Aid for Scientific Research No. 07671221 from the Ministry of Education, Science, Sports and Culture of Japan. This work was presented in part at the 58th general meeting of the Japanese Society of Hematology, in April 1996.


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