Studies on the crystal structure of clotting factors and its binding proteins.

凝血因子及其结合蛋白晶体结构的研究。

• 批准号: 13480197
• 负责人: MORITA Takashi
• 金额: $ 9.66万
• 依托单位: MEIJI PHARMACEUTICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13480197/
• 关键词: carboxyglutamic acid (Gla) domains; factor X; factor IX; Mg^<2+> ions; collagen receptor; glycoprotein(GP) Ia; IIa; EMS16; X因子; X因子結合タンパク質

We have recently isolated several C-type lectin-like proteins(CLPs) with a variety of biological activities, including anticoagulant- and platelet-modulating activities. The crystal structures ofγ-carboxyglutamic acid (Gla) domains of coagulation factors X and IX have been clarified in structural studies of complexes between the Gla domains of factor X and X-bp (a venom CLP) and between the Gla domain of factor IX and IX-bp (a venom CLP). Our recent results clearly suggest that Mg^<2+> ions are required to maintain native conformation and in vivo function of factor IX Gla domain during blood coagulation.EMS16 from the venom of Echis multisquamatus binds to the collagen receptor, integrin α2β1,also known as glycoprotein(GP) Ia/IIa, and specifically inhibits collagen binding. We have reported the crystal structure of EMS16 in complex with recombinant integrin α2-I domain that plays a central role in collagen binding. The structure of the complex at 1.9 Å resolution revealed that the collagen-binding site of the α2-I domain is covered completely by the bound EMS16. This blockage by EMS16 appears to spatially inhibit collagen binding to the α2-I domain.

我们最近分离了几种具有多种生物活性的c型凝集素样蛋白（CLPs），包括抗凝血和血小板调节活性。凝血因子X和IX的γ-羧基谷氨酸（Gla）结构域的晶体结构已在因子X和X-bp（一种毒液CLP）的Gla结构域之间以及因子IX和IX-bp（一种毒液CLP）的Gla结构域之间的配合物的结构研究中得到澄清。我们最近的研究结果清楚地表明，在凝血过程中，需要Mg^<2+ b>离子来维持IX Gla结构域的天然构象和体内功能。来自多鳞棘鱼毒液的EMS16与胶原受体整合素α2β1（也称为糖蛋白（GP） Ia/IIa）结合，特异性抑制胶原结合。我们已经报道了EMS16与重组整合素α2-I结构域复合物的晶体结构，该结构域在胶原结合中起核心作用。1.9 Å分辨率下的配合物结构显示，结合的EMS16完全覆盖了α2-I结构域的胶原结合位点。EMS16的这种阻断似乎在空间上抑制了胶原与α2-I结构域的结合。

项目成果

Criystal structure of Mg^<2+>-and Ca^<2+>-bound Gla domain of factor IX complexed with binding protein.

与结合蛋白复合的因子IX的Mg ^ 2 -和Ca ^ 2 -结合Gla结构域的晶体结构。

• 发表时间: 2003
• 期刊: J.Biol.Chem. 278
• 作者: Shikamoto Y.;Morita T.;Fujimoto Z.;Mizuno H.
• 通讯作者: Mizuno H.

The determination of plasma prothrombin level by Ca^<2+>-dependent prothrombin activator (CA-1) during warfarin anticoagulation.

华法林抗凝期间Ca^2依赖性凝血酶原激活剂(CA-1)测定血浆凝血酶原水平。

• 发表时间: 2001
• 期刊: J.Heart Valve Dis. 10
• 作者: 岩橋 英彦ら

Purification and characterization of a new RGD/KGD-containing dimeric disintegrin, piscivostatin, from the venom of Agkistrodon piscivorus piscivorus : The unique effect of piscivostatin on platelet aggregation.

从Agkistrodon piscivorus piscivorus的毒液中纯化和表征一种新的含有RGD/KGD的二聚解整合素piscivostatin：piscivostatin对血小板聚集的独特作用。

• 发表时间: 2001
• 期刊: J.Biochem. 130
• 作者: 奥田 大樹ら

山崎 泰男: "Snake venom vascular endothelial growth factors (VEGFs) exhibit potent activity through their specific recognition of KDR (VEGF receptor 2)"J.Biol.Chem.. 278(5). 51985-51988 (2003)

Yasuo Yamazaki：“蛇毒血管内皮生长因子 (VEGF) 通过其对 KDR（VEGF 受体 2）的特异性识别而表现出有效的活性”J.Biol.Chem.. 278(5) (2003)。

Structures and functions of snake venom CLPs (C-type lectin-like proteins) with anticoagulant-, procoagulant-, and platelet-modulating activities.

• DOI: 10.1016/j.toxicon.2005.02.021
• 发表时间: 2005-06
• 期刊: Toxicon : official journal of the International Society on Toxinology
• 作者: T. Morita