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恒河猴(猕猴)凝血因子VII的全长cDNA克隆及蛋白质三维结构建模

Full-length cDNA cloning and protein three-dimensional structure modeling of factor VII of rhesus monkey, Macaca mulatta.

作者信息

Wang Jiandong, Tan Weidong, Chen Younan, Lu Xiaofeng, Lu Yanrong, Qin Shengfang, Li Shengfu, Bu Hong, Li Youping, Cheng Jingqiu

机构信息

Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu 610041, PR China.

出版信息

Blood Cells Mol Dis. 2008 Mar-Apr;40(2):237-43. doi: 10.1016/j.bcmd.2007.08.003. Epub 2007 Oct 23.

DOI:10.1016/j.bcmd.2007.08.003
PMID:17936652
Abstract

FVII is a vitamin K dependent serine protease that plays a key role in extrinsic coagulation pathway. In this paper, we report the full-length cDNA sequences of rhesus monkey FVII. The full-length cDNA has 2424 bp, and predicts an open reading frame of 1416 bp corresponding to 472 amino acids. The deduced protein sequence of rhesus monkey FVII indicates the functional domains including signal peptide, Gla domain, two EGF domains, and catalytic domain. Rhesus monkey FVII is highly homologous to human FVII with amino acid identity of 91.0%. Comparison of three-dimensional protein structure shows high conservation between them. The important functional sites such as the N-terminal gamma-carboxyglutamic acids of the Gla domain, the Ca(2+) binding region of the EGF I domain, the TF binding region, the active site binding cleft, and the macromolecular substrate binding exosite of trypsin domain are all well conserved in FVII of rhesus monkey. Prothrombin time test shows rhesus monkey FVII has a similar clotting time with that of human. This study of rhesus monkey FVII might be helpful for understanding the function compatibility of human and rhesus monkey FVII, which is beneficial for the study of xenotransplantation.

摘要

凝血因子VII是一种维生素K依赖的丝氨酸蛋白酶,在外源性凝血途径中起关键作用。在本文中,我们报道了恒河猴凝血因子VII的全长cDNA序列。该全长cDNA有2424 bp,预测的开放阅读框为1416 bp,对应472个氨基酸。恒河猴凝血因子VII推导的蛋白质序列显示其功能域包括信号肽、Gla结构域、两个表皮生长因子(EGF)结构域和催化结构域。恒河猴凝血因子VII与人类凝血因子VII高度同源,氨基酸同一性为91.0%。蛋白质三维结构比较显示它们之间具有高度保守性。Gla结构域的N端γ-羧基谷氨酸、EGF I结构域的Ca(2+)结合区域、组织因子(TF)结合区域、活性位点结合裂隙以及胰蛋白酶结构域的大分子底物结合外位点等重要功能位点在恒河猴凝血因子VII中均得到很好的保守。凝血酶原时间测试表明恒河猴凝血因子VII与人的凝血时间相似。对恒河猴凝血因子VII的这项研究可能有助于理解人类和恒河猴凝血因子VII的功能兼容性,这对异种移植研究有益。

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Full-length cDNA cloning and protein three-dimensional structure modeling of factor VII of rhesus monkey, Macaca mulatta.恒河猴(猕猴)凝血因子VII的全长cDNA克隆及蛋白质三维结构建模
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Haematologica. 2004 Dec;89(12):1504-9.

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