6FYM

Human PARP14 (ARTD8), catalytic fragment in complex with inhibitor ITK1

6FYM の概要

• エントリーDOI: 10.2210/pdb6fym/pdb
• 分子名称: Poly [ADP-ribose] polymerase 14, 7,8-dimethyl-2-(pyrimidin-2-ylsulfanylmethyl)-3~{H}-quinazolin-4-one, NITRATE ION, ... (4 entities in total)
• 機能のキーワード: adp-ribosylation, inhibitor complex, transferase domain, transferase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 89791.82

構造登録者

Karlberg, T.,Thorsell, A.G.,Kirby, I.T.,Sreenivasan, R.,Cohen, M.S.,Schuler, H. (登録日: 2018-03-12, 公開日: 2019-02-20, 最終更新日: 2024-11-20)

主引用文献

Kirby, I.T.,Kojic, A.,Arnold, M.R.,Thorsell, A.G.,Karlberg, T.,Vermehren-Schmaedick, A.,Sreenivasan, R.,Schultz, C.,Schuler, H.,Cohen, M.S.
A Potent and Selective PARP11 Inhibitor Suggests Coupling between Cellular Localization and Catalytic Activity.
Cell Chem Biol, 25:1547-1553.e12, 2018

PubMed Abstract: Poly-ADP-ribose polymerases (PARPs1-16) play pivotal roles in diverse cellular processes. PARPs that catalyze poly-ADP-ribosylation (PARylation) are the best characterized PARP family members because of the availability of potent and selective inhibitors for these PARPs. There has been comparatively little success in developing selective small-molecule inhibitors of PARPs that catalyze mono-ADP-ribosylation (MARylation), limiting our understanding of the cellular role of MARylation. Here we describe the structure-guided design of inhibitors of PARPs that catalyze MARylation. The most selective analog, ITK7, potently inhibits the MARylation activity of PARP11, a nuclear envelope-localized PARP. ITK7 is greater than 200-fold selective over other PARP family members. Using live-cell imaging, we show that ITK7 causes PARP11 to dissociate from the nuclear envelope. These results suggest that the cellular localization of PARP11 is regulated by its catalytic activity.

PubMed: 30344052
DOI: 10.1016/j.chembiol.2018.09.011

実験手法

X-RAY DIFFRACTION (2.15 Å)