WEKO3
アイテム
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新規血液凝固第Xa因子(FXa)阻害剤(R-020)およびその誘導体の単離と性質
http://hdl.handle.net/10191/38487
http://hdl.handle.net/10191/384879b1797e1-1c1b-48ed-bf67-cea5610c9b0d
名前 / ファイル | ライセンス | アクション |
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108(9)_681-696.pdf (3.2 MB)
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Item type | 紀要論文 / Departmental Bulletin Paper(1) | |||||
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公開日 | 2016-02-18 | |||||
タイトル | ||||||
タイトル | 新規血液凝固第Xa因子(FXa)阻害剤(R-020)およびその誘導体の単離と性質 | |||||
タイトル | ||||||
言語 | en | |||||
タイトル | 新規血液凝固第Xa因子(FXa)阻害剤(R-020)およびその誘導体の単離と性質 | |||||
言語 | ||||||
言語 | jpn | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | coagulation factor Xa | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | plasma kallikrein | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | site-directed mutagenesis | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | urinary trypsin inhibitor | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | 血液凝固第 Xa 因子 | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | 血漿カリクレイン | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | 部位特異的突然変異 | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | 尿由来トリプシンインヒビター | |||||
資源タイプ | ||||||
資源 | http://purl.org/coar/resource_type/c_6501 | |||||
タイプ | departmental bulletin paper | |||||
その他のタイトル | ||||||
その他のタイトル | Isolation and Characterization of Novel Blood Coagulation Factor Xa (FXa) Inhibitor (R-020) and its Variants | |||||
著者 |
新居, 淳
× 新居, 淳 |
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著者別名 | ||||||
識別子 | 119174 | |||||
識別子Scheme | WEKO | |||||
姓名 | Nii, Atsushi | |||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Urinary trypsin inhibitor (UTI) isolated from human urine is an acidic glycoprotein with molecular weight of 67,000 and is known to inhibit trypsin, plasmin, leucocyte elastase, α-chymotrypsin and other enzymes. UTI is composed of two Kunitz-type domains and the second domain is responsible for its antitryptic activity. In order to determine the detailed inhibitory spectrum of the second Kunitz-type domain of UTI (R-020) against various proteases, I cloned two types of R-020 cDNAs: one encodes the 70-amino acid sequence from the 78th amino acid (Thr) to the C-terminal (R-020 TN70) and the other encodes the 68-amino acid sequence from the 80th (Ala) to the C-terminal (R-020, AN68). Their products are secreted into the cultured supernatant of E.coli JE5505 transformants. R-020 TN70 and R-020 AN68 purified from the cultured supernatant inhibited not only human trypsin, human plasmin, human leucocyte elastase and humanα-chymotrypsin which were already known to be inhibited by UTI but also the human blood coagulation factor Xa and plasma kallikrein. Furthermore, to increase the FXa inhibitory activity I constructed a model of the structure of the R-020 TN70-FXa complex with reference to that of bovine pancreatic trypsin inhibitor-bovine trypsin complex and investigated the binding state of R--20 TN70 and FXa. Based on this information, one amino acid of R-020 TN70 and AN68 was substituted with recombinant DNA technology. The inhibitory effect of the product on FXa was increased in four variants after single amino acid substitution. Four other variants with two amino acids substitution modified by combining the above mentioned single amino acid substitution showed an enhanced inhibitory effect on FXa in comparison with those with single amino acid substitution. Because the electrostatic interaction within these R-020 variants-FXa complexes seemed stronger, this increase in their inhibitory effect on FXa was speculated to be a consequence of more potent binding between the enzyme and the inhibitors. | |||||
書誌情報 |
新潟医学会雑誌 en : 新潟医学会雑誌 巻 108, 号 9, p. 681-696, 発行日 1994-09 |
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出版者 | ||||||
出版者 | 新潟医学会 | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 00290440 | |||||
書誌レコードID | ||||||
収録物識別子タイプ | NCID | |||||
収録物識別子 | AN00182415 | |||||
著者版フラグ | ||||||
値 | publisher |