4BJB

Crystal structure of human tankyrase 2 in complex with PJ-34

4BJB の概要

• エントリーDOI: 10.2210/pdb4bjb/pdb
• 関連するPDBエントリー: 4BJ9
• 分子名称: TANKYRASE-2, SULFATE ION, GLYCEROL, ... (6 entities in total)
• 機能のキーワード: transferase, diphtheria toxin like fold, adp- ribosylation, inhibitor
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Cytoplasm: Q9H2K2
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 27944.73

構造登録者

Haikarainen, T.,Narwal, M.,Lehtio, L. (登録日: 2013-04-17, 公開日: 2013-12-11, 最終更新日: 2024-05-08)

主引用文献

Haikarainen, T.,Narwal, M.,Joensuu, P.,Lehtio, L.
Evaluation and Structural Basis for the Inhibition of Tankyrases by Parp Inhibitors.
Acs Med.Chem.Lett., 5:18-, 2014

PubMed Abstract: Tankyrases, an enzyme subfamily of human poly(ADP-ribosyl)polymerases, are potential drug targets especially against cancer. We have evaluated inhibition of tankyrases by known PARP inhibitors and report five cocrystal structures of the most potent compounds in complex with human tankyrase 2. The inhibitors include the small general PARP inhibitors Phenanthridinone, PJ-34, and TIQ-A as well as the more advanced inhibitors EB-47 and rucaparib. The compounds anchor to the nicotinamide subsite of tankyrase 2. Crystal structures reveal flexibility of the ligand binding site with implications for drug development against tankyrases and other ADP-ribosyltransferases. EB-47 mimics the substrate NAD(+) and extends from the nicotinamide to the adenosine subsite. The clinical ARTD1 inhibitor candidate rucaparib was the most potent tankyrase inhibitor identified (24 and 14 nM for tankyrases), which indicates that inhibition of tankyrases would affect the cellular responses of this compound.

PubMed: 24900770
DOI: 10.1021/ML400292S

実験手法

X-RAY DIFFRACTION (2.3 Å)