Gettins P, Patston P A, Schapira M
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee.
Hematol Oncol Clin North Am. 1992 Dec;6(6):1393-408.
Serpins have a central role in regulating proteolysis in blood coagulation, fibrinolysis, and inflammation. Congenital serpin deficiencies cause specific clinical syndromes such as thrombosis with antithrombin III deficiency or emphysema with alpha 1-antitrypsin deficiency. Acquired serpin abnormalities have also been reported, for example, increased PAI-1, which is believed to represent a major risk factor for the development of thromboembolic complications. This article has reviewed the structure/function relationships of serpins and have presented ideas concerning their mechanism of action. The implications of this information for designing drugs that could interfere with serpin function has also been described, and mention has been made of the therapeutic potential of such compounds.
丝氨酸蛋白酶抑制剂在调节血液凝固、纤维蛋白溶解和炎症中的蛋白水解过程中起核心作用。先天性丝氨酸蛋白酶抑制剂缺乏会导致特定的临床综合征，如抗凝血酶III缺乏引起的血栓形成或α1-抗胰蛋白酶缺乏引起的肺气肿。也有获得性丝氨酸蛋白酶抑制剂异常的报道，例如，PAI-1增加，这被认为是血栓栓塞并发症发生的主要危险因素。本文综述了丝氨酸蛋白酶抑制剂的结构/功能关系，并提出了有关其作用机制的观点。还描述了这些信息对设计可能干扰丝氨酸蛋白酶抑制剂功能的药物的意义，并提及了此类化合物的治疗潜力。
