4HLH

Crystal structure of Tankyrase 2 in complex with 4'-fluoroflavone

4HLH の概要

• エントリーDOI: 10.2210/pdb4hlh/pdb
• 関連するPDBエントリー: 3U9H 3U9Y 3UA9 4HKI 4HKK 4HKN 4HL5 4HLF 4HLG 4HLK 4HLM 4HMH
• 分子名称: Tankyrase-2, ZINC ION, SULFATE ION, ... (8 entities in total)
• 機能のキーワード: protein-ligand complex, diphtheria toxin like fold transferase, adp-ribosylation, transferase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 55829.26

構造登録者

Narwal, M.,Haikarainen, T.,Lehtio, L. (登録日: 2012-10-17, 公開日: 2012-10-31, 最終更新日: 2024-02-28)

主引用文献

Narwal, M.,Haikarainen, T.,Fallarero, A.,Vuorela, P.M.,Lehtio, L.
Screening and structural analysis of flavones inhibiting tankyrases.
J.Med.Chem., 56:3507-3517, 2013

PubMed Abstract: Flavonoids are known for their beneficial effects on human health, and therefore the therapeutic potential of these compounds have been extensively studied. Flavone has been previously identified as a tankyrase inhibitor, and to further elucidate whether tankyrases would be inhibited by other flavonoids, we performed a systematic screening of tankyrase 2 inhibitory activity using 500 natural and naturally derived flavonoids covering nine different flavonoid classes. All identified tankyrase inhibitors were flavones. We report crystal structures of all the hit compounds in complex with the catalytic domain of human tankyrase 2. Flavone derivatives in all 10 crystal structures bind to the nicotinamide binding site of tankyrase 2. Potencies of the active flavones toward tankyrases vary between 50 nM and 1.1 μM, and flavones show up to 200-fold selectivity for tankyrases over ARTD1. The molecular details of the interactions revealed by cocrystal structures efficiently describe the properties of potent flavone derivatives inhibiting tankyrases.

PubMed: 23574272
DOI: 10.1021/jm3018783

実験手法

X-RAY DIFFRACTION (1.75 Å)