Lane D A, Kunz G, Olds R J, Thein S L
Department of Haematology, Charing Cross and Westminister Medical School, Hammersmith, London, UK.
Blood Rev. 1996 Jun;10(2):59-74. doi: 10.1016/s0268-960x(96)90034-x.
Antithrombin is the major proteinase inhibitor of thrombin and other blood coagulation proteinases. Antithrombin has two functional domains, a heparin binding site and a reactive centre (that complexes and inactivates the proteinase). Its deficiency results in an increased risk of venous thromboembolism. Appreciable progress has been made in recent years in understanding the structure and function of this protein, the genetic cause of inherited deficiency and its clinical consequence. The structure of antithrombin is now considered in terms of the models derived from X-ray crystallography, which have provided explanations for the function of its heparin interaction site and of its reactive loop. The structural organization of the antithrombin gene has been defined and numerous mutations have been identified that are responsible for antithrombin deficiency: these may reduce the level of the protein (Type I deficiency), alter the function of the protein (Type II deficiency, altering heparin binding or reactive sites), or even have multiple or 'pleiotropic effects' (Type II deficiency, altering both functional domains and the level of protein).
抗凝血酶是凝血酶和其他血液凝固蛋白酶的主要蛋白酶抑制剂。抗凝血酶有两个功能结构域，一个肝素结合位点和一个反应中心（与蛋白酶结合并使其失活）。其缺乏会导致静脉血栓栓塞风险增加。近年来，在了解该蛋白的结构和功能、遗传性缺乏的遗传原因及其临床后果方面取得了显著进展。现在根据X射线晶体学得出的模型来考虑抗凝血酶的结构，这些模型为其肝素相互作用位点和反应环的功能提供了解释。抗凝血酶基因的结构组织已被确定，并且已鉴定出许多导致抗凝血酶缺乏的突变：这些突变可能会降低蛋白质水平（I型缺乏），改变蛋白质功能（II型缺乏，改变肝素结合或反应位点），甚至具有多种或“多效性作用”（II型缺乏，改变两个功能结构域和蛋白质水平）。
