一种新型抗凝血酶结构域决定了蛋白酶的最终走向。
A novel antithrombin domain dictates the journey's end of a proteinase.
作者信息
Verhamme Ingrid M
机构信息
From the Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee 37232
出版信息
J Biol Chem. 2017 Oct 6;292(40):16521-16522. doi: 10.1074/jbc.H117.787325.
Abstract
Antithrombin (AT) is an anticoagulant serpin that irreversibly inactivates the clotting proteinases factor Xa and thrombin by forming covalent complexes with them. Mutations in its critical domains, such as those that impair the conformational rearrangement required for proteinase inactivation, increase the risk of venous thrombosis. Águila characterize for the first time the destabilizing effects of mutations in the region of AT that makes contact with the proteinase in the final acyl-enzyme complex. Their work adds new insight into the unique structural intricacies of the inhibitory mechanism.
摘要
抗凝血酶（AT）是一种抗凝丝氨酸蛋白酶抑制剂，通过与凝血蛋白酶因子Xa和凝血酶形成共价复合物，不可逆地使其失活。其关键结构域中的突变，如那些损害蛋白酶失活所需构象重排的突变，会增加静脉血栓形成的风险。阿吉拉首次描述了抗凝血酶中与最终酰基酶复合物中的蛋白酶接触区域的突变所产生的不稳定作用。他们的工作为抑制机制独特的结构复杂性提供了新的见解。
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