7OMC

Tankyrase 2 in complex with an inhibitor (OUL228)

これはPDB形式変換不可エントリーです。

7OMC の概要

• エントリーDOI: 10.2210/pdb7omc/pdb
• 分子名称: Poly [ADP-ribose] polymerase tankyrase-2, 8-propan-2-yloxy-4~{H}-thieno[2,3-c]isoquinolin-5-one, ZINC ION, ... (7 entities in total)
• 機能のキーワード: inhibitor, enzyme, 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: 50817.99

構造登録者

Sowa, S.T.,Lehtio, L. (登録日: 2021-05-21, 公開日: 2021-12-08, 最終更新日: 2024-01-31)

主引用文献

Maksimainen, M.M.,Murthy, S.,Sowa, S.T.,Galera-Prat, A.,Rolina, E.,Heiskanen, J.P.,Lehtio, L.
Analogs of TIQ-A as inhibitors of human mono-ADP-ribosylating PARPs.
Bioorg.Med.Chem., 52:116511-116511, 2021

PubMed Abstract: The scaffold of TIQ-A, a previously known inhibitor of human poly-ADP-ribosyltransferase PARP1, was utilized to develop inhibitors against human mono-ADP-ribosyltransferases through structure-guided design and activity profiling. By supplementing the TIQ-A scaffold with small structural changes, based on a PARP10 inhibitor OUL35, selectivity changed from poly-ADP-ribosyltransferases towards mono-ADP-ribosyltransferases. Binding modes of analogs were experimentally verified by determining complex crystal structures with mono-ADP-ribosyltransferase PARP15 and with poly-ADP-ribosyltransferase TNKS2. The best analogs of the study achieved 10-20-fold selectivity towards mono-ADP-ribosyltransferases PARP10 and PARP15 while maintaining micromolar potencies. The work demonstrates a route to differentiate compound selectivity between mono- and poly-ribosyltransferases of the human ARTD family.

PubMed: 34801828
DOI: 10.1016/j.bmc.2021.116511

実験手法

X-RAY DIFFRACTION (2.1 Å)