Suppr超能文献

增强凝血酶原复合物的抗凝特性。

Enhancing the anticoagulant profile of meizothrombin.

作者信息

Stojanovski Bosko M, Pelc Leslie A, Zuo Xiaobing, Pozzi Nicola, Cera Enrico Di

机构信息

Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, MO 63104 USA.

X-Ray Science Division, Argonne National Laboratory, Argonne, Illinois 60439, USA.

出版信息

Biomol Concepts. 2018 Dec 26;9(1):169-175. doi: 10.1515/bmc-2018-0016.

Abstract

Meizothrombin is an active intermediate generated during the proteolytic activation of prothrombin to thrombin in the penultimate step of the coagulation cascade. Structurally, meizothrombin differs from thrombin because it retains the auxiliary Gla domain and two kringles. Functionally, meizothrombin shares with thrombin the ability to cleave procoagulant (fibrinogen), prothrombotic (PAR1) and anticoagulant (protein C) substrates, although its specificity toward fibrinogen and PAR1 is less pronounced. In this study we report information on the structural architecture of meizothrombin resolved by SAXS and single molecule FRET as an elongated arrangement of its individual domains. In addition, we show the properties of a meizothrombin construct analogous to the anticoagulant thrombin mutant W215A/E217A currently in Phase I for the treatment of thrombotic complications and stroke. The findings reveal new structural and functional aspects of meizothrombin that advance our understanding of a key intermediate of the prothrombin activation pathway.

摘要

中凝血酶是在凝血级联反应倒数第二步中,凝血酶原向凝血酶蛋白水解激活过程中产生的一种活性中间体。在结构上,中凝血酶与凝血酶不同,因为它保留了辅助性γ-羧基谷氨酸(Gla)结构域和两个kringle结构域。在功能上,中凝血酶与凝血酶一样,具有切割促凝血(纤维蛋白原)、促血栓形成(蛋白酶激活受体1,PAR1)和抗凝血(蛋白C)底物的能力,尽管其对纤维蛋白原和PAR1的特异性不太明显。在本研究中,我们报告了通过小角X射线散射(SAXS)和单分子荧光共振能量转移(FRET)解析的中凝血酶结构架构信息,其呈现为各个结构域的细长排列。此外,我们展示了一种中凝血酶构建体的特性,该构建体类似于目前正处于治疗血栓并发症和中风的I期临床试验阶段的抗凝血凝血酶突变体W215A/E217A。这些发现揭示了中凝血酶新的结构和功能方面,增进了我们对凝血酶原激活途径关键中间体的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1389/6825329/4c9631fb8ba5/nihms-1056888-f0001.jpg

相似文献

1
Enhancing the anticoagulant profile of meizothrombin.增强凝血酶原复合物的抗凝特性。
Biomol Concepts. 2018 Dec 26;9(1):169-175. doi: 10.1515/bmc-2018-0016.
4
Binding of hirudin to meizothrombin.水蛭素与中间凝血酶的结合。
Protein Eng. 1998 Aug;11(8):715-21. doi: 10.1093/protein/11.8.715.
10
Meizothrombin is an unexpectedly zymogen-like variant of thrombin.美泽血栓素是一种出乎意料的类酶原变体的凝血酶。
J Biol Chem. 2012 Aug 31;287(36):30414-25. doi: 10.1074/jbc.M112.394809. Epub 2012 Jul 19.

引用本文的文献

1
Conformation of factor Xa in solution revealed by single-molecule spectroscopy.溶液中因子 Xa 的构象通过单分子光谱法揭示。
J Thromb Haemost. 2024 Oct;22(10):2767-2772. doi: 10.1016/j.jtha.2024.07.003. Epub 2024 Jul 11.
3
Cryo-EM structures of coagulation factors.凝血因子的冷冻电镜结构
Res Pract Thromb Haemost. 2022 Nov 2;6(7):e12830. doi: 10.1002/rth2.12830. eCollection 2022 Oct.
4
8
Zymogen and activated protein C have similar structural architecture.酶原和激活蛋白 C 具有相似的结构构象。
J Biol Chem. 2020 Nov 6;295(45):15236-15244. doi: 10.1074/jbc.RA120.014789. Epub 2020 Aug 27.

本文引用的文献

10
The transition of prothrombin to thrombin.凝血酶原向凝血酶的转化。
J Thromb Haemost. 2013 Jun;11 Suppl 1(0 1):265-76. doi: 10.1111/jth.12217.

文献检索

告别复杂PubMed语法,用中文像聊天一样搜索,搜遍4000万医学文献。AI智能推荐,让科研检索更轻松。

立即免费搜索

文件翻译

保留排版,准确专业,支持PDF/Word/PPT等文件格式,支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述,25分钟生成高质量综述,智能提取关键信息,辅助科研写作。

立即免费体验