Physiological role of oligosaccharides present in the first EGF-like domain of clotting factors VII and IX

凝血因子 VII 和 IX 的第一个 EGF 样结构域中存在的寡糖的生理作用

• 批准号: 03808023
• 负责人: KAWABATA Shun-ichiro
• 金额: $ 1.09万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-03808023/
• 关键词: Coagulation factor VII; Coagulation factor IX; EGF-like domain; Oligosaccharide; Glycosidase; グリコシダ-ゼ

We have found recently a new trisaccharide chain linked to serine 53 and serine 52 located in the first epidermal growth factor-like domain of bovine factors VII and IX.Bovine factors VII and IX were treated with several glycosidases,alpha-xylosidase, beta-xylosidase,and o-glycanase to obtain the sugar-less proteins. None of the enzymes,however,could not release the sugar chains from the proteins. To figure out the physiological function of the sugar chains,we synthesized oligosaccharides including Glc-Xyl,Glc-Xyl-Xyl,Ser-Glc-Xyl, and Ser-Glc-Xyl-Xyl. However,these oligosaccharides had little or no effect on the activation of factor X by factor IXa in the presence of phospholipids,Ca^<2+>,and factor VII. Furthermore,they had no effect on the activation of factor X by factor VIIa in the presence of tissue factor,phospholipids, and Ca^<2+>.These results indicate that the oligosaccharides linked to the EGF-domain in factors VII and IX are not directly involved in the activation of extrinsic coagulation pathway.

我们最近发现了一个新的三糖链连接到丝氨酸53和丝氨酸52位于第一表皮生长因子样结构域的牛因子VII和IX。牛因子VII和IX的处理与几个糖苷酶，α-木糖苷酶，β-木糖苷酶，和O-聚糖酶，以获得无糖蛋白。然而，没有一种酶不能从蛋白质中释放糖链。为了弄清糖链的生理功能，我们合成了包括Glc-Xyl、Glc-Xyl-Xyl、Ser-Glc-Xyl和Ser-Glc-Xyl-Xyl的寡糖。然而，在磷脂、Ca^2+和因子VII存在的情况下，这些寡糖对因子IXa激活因子X的作用很小或没有作用。此外，在存在组织因子、磷脂和Ca^2+的情况下，它们对因子VIIa激活因子X没有影响。这些结果表明，与因子VII和IX中EGF结构域连接的寡糖不直接参与外源性凝血途径的激活。

项目成果

Shouichi Higashi: "Tissue factor potentiates the factor VIIa-catalyzed hydrolysis of an ester substrate." Journal of Biological Chemistry. 267. 17990-17996 (1992)

Shouichi Higashi：“组织因子增强了因子 VIIa 催化的酯底物水解。”

S.Higashi et al: "Tissue factor potentiates the factor VIIa-catalyzed hydrolysis of an ester substrate" J.Biol.Chem. 267. 17990-17996 (1992)

S.Higashi 等人：“组织因子增强了因子 VIIa 催化的酯底物水解”J.Biol.Chem。

S.Iwanaga et al: Plenum Press,New York. A new trisaccharide sugar chain linked to a serine residue in the first EGF-like domain of clotting factors VII,and IX and protein Z.in Fibrinogen,Thrombosis Coagulation,and Fibrinolysis(C.Y.Liu and S.Chien,eds), 12

S.Iwanaga 等人：Plenum Press，纽约。

S.Hase et al: "The structure of(xylose)_2-glucose-o-serine 53 found in the first epidermal growth factor-like domain of bovine blood clotting factor IX.J.Biol" Chem. 265. 1858-1861 (1990)

S.Hase 等人：“在牛凝血因子 IX 的第一个表皮生长因子样结构域中发现的（木糖）_2-葡萄糖-o-丝氨酸 53 的结构。J.Biol”Chem。

S.Kawabata et al: "A microsomal endopeptidase from liver with substrate specificity for processing proproteins such as the vitamin K-dependent proteins of plasma" J.Biol.Chem. 267. 10331-10336 (1992)

S.Kawabata 等人：“一种来自肝脏的微粒体内肽酶，具有底物特异性，可用于处理前蛋白，例如血浆中的维生素 K 依赖性蛋白”J.Biol.Chem。