Coughlin Paul B
Australian Centre for Blood Diseases, Monash University, Prahran.
FEBS J. 2005 Oct;272(19):4852-7. doi: 10.1111/j.1742-4658.2005.04881.x.
Much of the basic biochemistry of antiplasmin was described more than 20 years ago and yet it remains an enigmatic member of the serine protease inhibitor (serpin) family. It possesses all of the characteristics of other inhibitory serpins but in addition it has unique N- and C-terminal extensions which significantly modify its activities. The N-terminus serves as a substrate for Factor XIIIa leading to crosslinking and incorporation of antiplasmin into a clot as it is formed. Although free antiplasmin is an excellent inhibitor of plasmin, the fibrin bound form of the serpin appears to be the major regulator of clot lysis. The C-terminal portion of antiplasmin is highly conserved between species and contains several charged amino acids including four lysines with one of these at the C-terminus. This portion of the molecule mediates the initial interaction with plasmin and is a key component of antiplasmin's rapid and efficient inhibitory mechanism. Studies of mice with targeted deletion of antiplasmin have confirmed its importance as a major regulator of fibrinolysis and re-emphasized its value as a potential therapeutic target.
抗纤溶酶的许多基本生物化学特性在20多年前就已被描述，但它仍然是丝氨酸蛋白酶抑制剂（serpin）家族中一个神秘的成员。它具备其他抑制性丝氨酸蛋白酶抑制剂的所有特征，但此外它还有独特的N端和C端延伸结构，这些结构显著改变了它的活性。N端作为因子XIIIa的底物，导致抗纤溶酶在形成凝块时发生交联并融入凝块中。尽管游离的抗纤溶酶是纤溶酶的优秀抑制剂，但丝氨酸蛋白酶抑制剂的纤维蛋白结合形式似乎是凝块溶解的主要调节因子。抗纤溶酶的C端部分在物种间高度保守，包含几个带电荷的氨基酸，其中包括四个赖氨酸，其中一个位于C端。分子的这一部分介导了与纤溶酶的初始相互作用，是抗纤溶酶快速高效抑制机制的关键组成部分。对靶向缺失抗纤溶酶的小鼠的研究证实了它作为纤维蛋白溶解主要调节因子的重要性，并再次强调了它作为潜在治疗靶点的价值。
