2ZZU

Human Factor VIIA-Tissue Factor Complexed with ethylsulfonamide-D-5-(3-carboxybenzyloxy)-Trp-Gln-p-aminobenzamidine

2ZZU の概要

• エントリーDOI: 10.2210/pdb2zzu/pdb
• 関連するPDBエントリー: 1WQV 1WSS 1WTG 1WUN 1WV7 2ZWL
• 分子名称: Factor VII light chain, Factor VII heavy chain, Tissue factor, ... (8 entities in total)
• 機能のキーワード: serine protease, blood coagulation, cleavage on pair of basic residues, disease mutation, egf-like domain, gamma-carboxyglutamic acid, glycoprotein, hydrolase, hydroxylation, protease, zymogen, lipoprotein, membrane, palmitate, transmembrane, hydrolase-blood clotting complex, secreted, hydrolase/blood clotting
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Secreted: P08709 P08709; Isoform 1: Membrane; Single-pass type I membrane protein. Isoform 2: Secreted: P13726
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 71698.53

構造登録者

Kadono, S.,Sakamoto, A.,Kikuchi, Y.,Oh-Eda, M.,Yabuta, N.,Koga, T.,Hattori, K.,Shiraishi, T.,Haramura, M.,Sato, H.,Ohta, M.,Kozono, T. (登録日: 2009-02-25, 公開日: 2009-03-24, 最終更新日: 2023-11-15)

主引用文献

Shiraishi, T.,Kadono, S.,Haramura, M.,Kodama, H.,Ono, Y.,Iikura, H.,Esaki, T.,Koga, T.,Hattori, K.,Watanabe, Y.,Sakamoto, A.,Yoshihashi, K.,Kitazawa, T.,Esaki, K.,Ohta, M.,Sato, H.,Kozono, T.
Design and synthesis of peptidomimetic factor VIIa inhibitors
Chem.Pharm.Bull., 58:38-44, 2010

PubMed Abstract: Selective factor VIIa-tissue factor complex (FVIIa/TF) inhibition is regarded as a promising target for developing new anticoagulant drugs. In previous reports, we described a S3 subsite found in the X-ray crystal structure of compound 2 that bound to FVIIa/soluble tissue factor (sTF). Based on the X-ray crystal structure information and with the aim of improving the inhibition activity for FVIIa/TF and selectivity against other serine proteases, we synthesized derivatives by introducing substituents at position 5 of the indole ring of compound 2. Among them, compound 16 showed high selectivity against other serine proteases. Contrary to our expectations, compound 16 did not occupy the S3-subsite; X-ray structure analysis revealed that compound 16 improved selectivity by forming hydrogen bonds with Gln217, Thr99 and Asn100.

PubMed: 20045964
DOI: 10.1248/cpb.58.38

実験手法

X-RAY DIFFRACTION (2.5 Å)