TAILIEUCHUNG - Báo cáo khoa học: Small-molecule modulators of zymogen activation in the fibrinolytic and coagulation systems

The coagulation and fibrinolytic systems are central to the hemostatic mechanism, which works promptly on vascular injury and tissue damage. The rapid response is generated by specific molecular interactions between components in these systems. Thus, the regulation mechanism of the sys-tems is programmed in each component, as exemplified by the elegant pro-cesses in zymogen activation. | ỊFEBS Journal REVIEW ARTICLE Small-molecule modulators of zymogen activation in the fibrinolytic and coagulation systems Keiji Hasumi Shingo Yamamichi and Tomotaka Harada Department of Applied BiologicalScience Tokyo Noko University Japan Keywords coagulation conformation fibrinolysis plasma hyaluronan-binding protein plasminogen plasminogen activator protease prothrombin urokinase zymogen activation Correspondence K. Hasumi Department of Applied Biological Science Tokyo Noko University 3-5-8 Saiwaicho Fuchu-shi Tokyo 183-8509 Japan Fax 81 42 367 5708 Tel 81 42 367 5710 E-mail hasumi@ Received 29 April2010 revised 8 July 2010 accepted 19 July 2010 doi The coagulation and fibrinolytic systems are central to the hemostatic mechanism which works promptly on vascular injury and tissue damage. The rapid response is generated by specific molecular interactions between components in these systems. Thus the regulation mechanism of the systems is programmed in each component as exemplified by the elegant processes in zymogen activation. This review describes recently identified small molecules that modulate the activation of zymogens in the fibrinolytic and coagulation systems. Introduction The coagulation and fibrinolytic systems are central to the hemostatic mechanism. This mechanism is primarily responsible for preventing blood leakage and secondarily for tissue repair and wound healing. Interactions between a variety of enzymes and nonenzyme components account for the finely regulated processes in the coagulation and fibrinolytic systems 1 2 . Most of the enzymes in these systems are serine proteases circulating as either inactive proenzyme or proenzyme forms with very low activity. Thus their activation is a prerequisite for their function whereas their inhibition or inactivation is also important in the regulation and termination of the reaction. Activation of the zymogens is a consequence of a conformational change .

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