1NDW

Crystal Structure of Adenosine Deaminase Complexed with FR221647

1NDW の概要

• エントリーDOI: 10.2210/pdb1ndw/pdb
• 関連するPDBエントリー: 1NDV 1NDY 1NDZ
• 分子名称: Adenosine Deaminase, ZINC ION, 1-((1R)-1-(HYDROXYMETHYL)-3-PHENYLPROPYL)-1H-IMIDAZOLE-4-CARBOXAMIDE, ... (4 entities in total)
• 機能のキーワード: sbdd, tim-barrel, 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: 40666.38

構造登録者

Kinoshita, T. (登録日: 2002-12-09, 公開日: 2003-12-09, 最終更新日: 2024-03-13)

主引用文献

Terasaka, T.,Kinoshita, T.,Kuno, M.,Nakanishi, I.
A highly potent non-nucleoside adenosine deaminase inhibitor: efficient drug discovery by intentional lead hybridization
J.Am.Chem.Soc., 126:34-35, 2004

PubMed Abstract: We disclose herein the rapid discovery of the first highly potent (Ki = 7.7 nM) non-nucleoside adenosine deaminase (ADA) inhibitor based on the rational hybridization of two structurally distinct leads. Two micromolar inhibitors were discovered by a parallel rational design and random screening program, and individual crystal structures of bovine ADA in complexation with these inhibitors revealed several unknown binding sites and distinct binding modes. Using this information as the starting point, highly effective lead hybridization was achieved in only two structure-based drug design iterations. The conceptual approach illustrated by this example promises to be broadly useful in the search for new chemical entities and can contribute greatly to improve the overall efficiency and speed of drug discovery.

PubMed: 14709046
DOI: 10.1021/ja038606l

実験手法

X-RAY DIFFRACTION (2 Å)