4BFP

Crystal structure of human tankyrase 2 in complex with WIKI4

4BFP の概要

• エントリーDOI: 10.2210/pdb4bfp/pdb
• 分子名称: TANKYRASE-2, 2-[3-[[4-(4-methoxyphenyl)-5-pyridin-4-yl-1,2,4-triazol-3-yl]sulfanyl]propyl]benzo[de]isoquinoline-1,3-dione, SULFATE ION, ... (5 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)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 56157.78

構造登録者

Haikarainen, T.,Narwal, M.,Lehtio, L. (登録日: 2013-03-21, 公開日: 2013-06-19, 最終更新日: 2024-05-08)

主引用文献

Haikarainen, T.,Venkannagari, H.,Narwal, M.,Obaji, E.,Lee, H.,Nkizinkiko, Y.,Lehtio, L.
Structural Basis and Selectivity of Tankyrase Inhibition by a Wnt Signaling Inhibitor Wiki4
Plos One, 8:65404-, 2013

PubMed Abstract: Recently a novel inhibitor of Wnt signaling was discovered. The compound, WIKI4, was found to act through tankyrase inhibition and regulate β-catenin levels in many cancer cell lines and human embryonic stem cells. Here we confirm that WIKI4 is a high potency tankyrase inhibitor and that it selectively inhibits tankyrases over other ARTD enzymes tested. The binding mode of the compound to tankyrase 2 was determined by protein X-ray crystallography to 2.4 Å resolution. The structure revealed a novel binding mode to the adenosine subsite of the donor NAD(+) binding groove of the catalytic domain. Our results form a structural basis for further development of potent and selective tankyrase inhibitors based on the WIKI4 scaffold.

PubMed: 23762361
DOI: 10.1371/JOURNAL.PONE.0065404

実験手法

X-RAY DIFFRACTION (2.4 Å)