4X8S

FACTOR VIIA IN COMPLEX WITH THE INHIBITOR 4-BROMO-2-METHOXYPHENOL

4X8S の概要

• エントリーDOI: 10.2210/pdb4x8s/pdb
• 関連するPDBエントリー: 4X8T 4X8U 4X8V
• 分子名称: Factor VIIa (Heavy Chain), Factor VIIa (Light Chain), 4-bromo-2-methoxyphenol, ... (7 entities in total)
• 機能のキーワード: glycoprotein, hydrolase, 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: 35037.73

構造登録者

Wei, A. (登録日: 2014-12-10, 公開日: 2015-03-25, 最終更新日: 2024-11-20)

主引用文献

Cheney, D.L.,Bozarth, J.M.,Metzler, W.J.,Morin, P.E.,Mueller, L.,Newitt, J.A.,Nirschl, A.H.,Rendina, A.R.,Tamura, J.K.,Wei, A.,Wen, X.,Wurtz, N.R.,Seiffert, D.A.,Wexler, R.R.,Priestley, E.S.
Discovery of Novel P1 Groups for Coagulation Factor VIIa Inhibition Using Fragment-Based Screening.
J.Med.Chem., 58:2799-2808, 2015

PubMed Abstract: A multidisciplinary, fragment-based screening approach involving protein ensemble docking and biochemical and NMR assays is described. This approach led to the discovery of several structurally diverse, neutral surrogates for cationic factor VIIa P1 groups, which are generally associated with poor pharmacokinetic (PK) properties. Among the novel factor VIIa inhibitory fragments identified were aryl halides, lactams, and heterocycles. Crystallographic structures for several bound fragments were obtained, leading to the successful design of a potent factor VIIa inhibitor with a neutral lactam P1 and improved permeability.

PubMed: 25764119
DOI: 10.1021/jm501982k

実験手法

X-RAY DIFFRACTION (2.1 Å)