5ADR

Crystal structure of human tankyrase 2 in complex with OD38

5ADR の概要

• エントリーDOI: 10.2210/pdb5adr/pdb
• 関連するPDBエントリー: 5ADQ 5ADS 5ADT
• 分子名称: TANKYRASE-2, SULFATE ION, N-(4-(((4-(4-methoxyphenyl)oxan-4- yl)methyl)carbamoyl)phenyl)-5-methylfuran-2-carboxamide, ... (7 entities in total)
• 機能のキーワード: transferase, protein-ligand complex, diphtheria toxin like fold, adp- ribosylation, transferase-transferase inhibitor complex
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• 細胞内の位置: Cytoplasm: Q9H2K2 Q9H2K2
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 27955.64

構造登録者

Haikarainen, T.,Lehtio, L. (登録日: 2015-08-24, 公開日: 2016-01-13, 最終更新日: 2024-05-08)

主引用文献

Haikarainen, T.,Waaler, J.,Ignatev, A.,Nkizinkiko, Y.,Venkannagari, H.,Obaji, E.,Krauss, S.,Lehtio, L.
Development and Structural Analysis of Adenosine Site Binding Tankyrase Inhibitors.
Bioorg.Med.Chem.Lett., 26:328-, 2016

PubMed Abstract: Tankyrases 1 and 2, the specialized members of the ARTD protein family, are druggable biotargets whose inhibition may have therapeutic potential against cancer, metabolic disease, fibrotic disease, fibrotic wound healing and HSV viral infections. We have previously identified a novel tankyrase inhibitor scaffold, JW55, and showed that it reduces mouse colon adenoma formation in vivo. Here we expanded the scaffold and profiled the selectivity of the compounds against a panel of human ARTDs. The scaffold also enables a fine modulation of selectivity towards either tankyrase 1 or tankyrase 2. In order to get insight about the binding mode of the inhibitors, we solved crystal structures of the compounds in complex with tankyrase 2. The compounds bind to the adenosine pocket of the catalytic domain and cause changes in the protein structure that are modulated by the chemical modifications of the compounds. The structural analysis allows further rational development of this compound class as a potent and selective tankyrase inhibitor.

PubMed: 26706174
DOI: 10.1016/J.BMCL.2015.12.018

実験手法

X-RAY DIFFRACTION (2.1 Å)