STRUCTURE AND FUNCTION OF HUMAN PLASMIN

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Human plasmin is an enzyme whose function is to dissolve fibrin blood clots. It consists of a light chain, which contains the catalytic site, and a heavy chain, which appears to be involved in interactions with other proteins such as fibrin and antiplasmin. The heavy chain consists of five homologous domains called "kringles", some of which contain binding cites for lysine and which appear to be involved in the regulation of fibrinolysis. Our goal is to elucidate the tertiary structures of kringles 1 and 4 to delineate their lysine binding sites, with the aim of understanding how these structures interact with fibrin, antiplasmin and other proteins. A variety of experimental techniques will be used, including immunochemical mapping, chemical modification, high resolution NMR spectroscopy and x-ray crystallography, to accomplish this goal.