1WTG

Human Factor Viia-Tissue Factor Complexed with ethylsulfonamide-D-biphenylalanine-Gln-p-aminobenzamidine

1WTG の概要

• エントリーDOI: 10.2210/pdb1wtg/pdb
• 関連するPDBエントリー: 1DAN 1WQV 1WSS
• 分子名称: Coagulation factor VII, Tissue factor, beta-D-glucopyranose, ... (8 entities in total)
• 機能のキーワード: serine protease, hydrolase-blood clotting complex, hydrolase/blood clotting
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 71585.45

構造登録者

Kadono, S.,Sakamoto, S.,Kikuchi, Y.,Oh-Eda, M.,Yabuta, N.,Kitazawa, K.,Yoshihashi, T.,Suzuki, T.,Koga, T.,Hattori, K.,Shiraishi, T.,Kodama, M.,Haramura, H.,Ono, Y.,Esaki, T.,Sato, H.,Watanabe, Y.,Itoh, S.,Ohta, M.,Kozono, T. (登録日: 2004-11-23, 公開日: 2005-11-23, 最終更新日: 2023-11-15)

主引用文献

Kadono, S.,Sakamoto, A.,Kikuchi, Y.,Oh-Eda, M.,Yabuta, N.,Yoshihashi, K.,Kitazawa, T.,Suzuki, T.,Koga, T.,Hattori, K.,Shiraishi, T.,Haramura, M.,Kodama, H.,Ono, Y.,Esaki, T.,Sato, H.,Watanabe, Y.,Itoh, S.,Ohta, M.,Kozono, T.
Novel interactions of large P3 moiety and small P4 moiety in the binding of the peptide mimetic factor VIIa inhibitor
Biochem.Biophys.Res.Commun., 326:859-865, 2005

PubMed Abstract: Selective factor VIIa-tissue factor complex (FVIIa/TF) inhibition is seen as a promising target for developing new anticoagulant drugs. A novel peptide mimetic factor VIIa inhibitor, ethylsulfonamide-d-biphenylalanine-Gln-p-aminobenzamidine, shows 100-fold selectivity against thrombin in spite of its large P3 moiety, unlike previously reported FVIIa/TF selective inhibitors. X-ray crystal structure analysis reveals that the large P3 moiety, d-biphenylalanine, and the small P4 moiety, ethylsulfonamide, make novel interactions with the 170-loop and Lys192 of FVIIa/TF, respectively, accompanying ligand-induced conformational changes of the 170-loop, Gln217, and Lys192. Structural comparisons of FVIIa with thrombin and amino acid sequence comparisons among coagulation serine proteases suggest that these interactions play an important role in achieving selective inhibition for FVIIa/TF.

PubMed: 15607748
DOI: 10.1016/j.bbrc.2004.11.108

実験手法

X-RAY DIFFRACTION (2.2 Å)