2E1W

Crystal structure of adenosine deaminase complexed with potent inhibitors

「1V78」から置き換えられました

2E1W の概要

• エントリーDOI: 10.2210/pdb2e1w/pdb
• 関連するPDBエントリー: 1V79 1V7A
• 分子名称: Adenosine deaminase, ZINC ION, 1-{(1R,2S)-2-HYDROXY-1-[2-(1-NAPHTHYL)ETHYL]PROPYL}-1H-IMIDAZOLE-4-CARBOXAMIDE, ... (4 entities in total)
• 機能のキーワード: beta barrel, zinc, hydrolase
• 由来する生物種: Bos taurus (cattle)
• 細胞内の位置: Cell membrane; Peripheral membrane protein; Extracellular side (By similarity): P56658
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 40730.47

構造登録者

Kinoshita, T. (登録日: 2006-10-30, 公開日: 2006-11-07, 最終更新日: 2024-03-13)

主引用文献

Terasaka, T.,Okumura, H.,Tsuji, K.,Kato, T.,Nakanishi, I.,Kinoshita, T.,Kato, Y.,Kuno, M.,Seki, N.,Naoe, Y.,Inoue, T.,Tanaka, K.,Nakamura, K.
Structure-Based Design and Synthesis of Non-Nucleoside, Potent, and Orally Bioavailable Adenosine Deaminase Inhibitors
J.Med.Chem., 47:2728-2731, 2004

PubMed Abstract: We disclose optimization efforts based on the novel non-nucleoside adenosine deaminase (ADA) inhibitor, 4 (K(i) = 680 nM). Structure-based drug design utilizing the crystal structure of the 4/ADA complex led to discovery of 5 (K(i) = 11 nM, BA = 30% in rats). Furthermore, from metabolic considerations, we discovered two inhibitors with improved oral bioavailability [6 (K(i) = 13 nM, BA = 44%) and 7 (K(i) = 9.8 nM, BA = 42%)]. 6 demonstrated in vivo efficacy in models of inflammation and lymphoma.

PubMed: 15139750
DOI: 10.1021/jm0499559

実験手法

X-RAY DIFFRACTION (2.5 Å)