4JZE

Structure of factor VIIA in complex with the inhibitor 2-{2-[(1-aminoisoquinolin-6-yl)carbamoyl]-6-methoxypyridin-3-yl}-5-{[(2S)-1-hydroxy-3,3-dimethylbutan-2-yl]carbamoyl}benzoic acid

4JZE の概要

• エントリーDOI: 10.2210/pdb4jze/pdb
• 関連するPDBエントリー: 4JZD 4JZF
• 分子名称: Factor VIIa (Heavy Chain), Factor VIIa (Light Chain), 2-{2-[(1-aminoisoquinolin-6-yl)carbamoyl]-6-methoxypyridin-3-yl}-5-{[(2S)-1-hydroxy-3,3-dimethylbutan-2-yl]carbamoyl}benzoic acid, ... (7 entities in total)
• 機能のキーワード: glycoprotein, serine protease, plasma, blood coagulation factor, protein inhibitor complex, calcium binding, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Secreted: P08709 P08709
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 35392.29

構造登録者

Wei, A.,Anumula, R. (登録日: 2013-04-02, 公開日: 2013-08-21, 最終更新日: 2024-10-16)

主引用文献

Bolton, S.A.,Sutton, J.C.,Anumula, R.,Bisacchi, G.S.,Jacobson, B.,Slusarchyk, W.A.,Treuner, U.D.,Wu, S.C.,Zhao, G.,Pi, Z.,Sheriff, S.,Smirk, R.A.,Bisaha, S.,Cheney, D.L.,Wei, A.,Schumacher, W.A.,Hartl, K.S.,Liu, E.,Zahler, R.,Seiler, S.M.
Discovery of nonbenzamidine factor VIIa inhibitors using a biaryl acid scaffold.
Bioorg.Med.Chem.Lett., 23:5239-5243, 2013

PubMed Abstract: In this Letter, we describe the synthesis of several nonamidine analogs of biaryl acid factor VIIa inhibitor 1 containing weakly basic or nonbasic P1 groups. 2-Aminoisoquinoline was found to be an excellent surrogate for the benzamidine group (compound 2) wherein potent inhibition of factor VIIa is maintained relative to most other related serine proteases. In an unanticipated result, the m-benzamide P1 (compounds 21a and 21b) proved to be a viable benzamidine replacement, albeit with a 20-40 fold loss in potency against factor VIIa.

PubMed: 23927973
DOI: 10.1016/j.bmcl.2013.06.028

実験手法

X-RAY DIFFRACTION (1.52 Å)