4GV2

Human ARTD3 (PARP3) - Catalytic domain in complex with inhibitor ME0354

4GV2 の概要

• エントリーDOI: 10.2210/pdb4gv2/pdb
• 関連するPDBエントリー: 4GV0 4GV4
• 分子名称: Poly [ADP-ribose] polymerase 3, 3-(4-oxo-3,4-dihydroquinazolin-2-yl)-N-[(1R)-1-(pyridin-2-yl)ethyl]propanamide, DIMETHYL SULFOXIDE, ... (4 entities in total)
• 機能のキーワード: nad, adp-ribose, parp3, artd3, artd transferase domain, adp- ribosylation, transferase-transferase inhibitor complex, transferase, adp-ribosylation, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: Q9Y6F1
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 40152.57

構造登録者

Karlberg, T.,Thorsell, A.G.,Lindgren, A.E.G.,Ekblad, T.,Spjut, S.,Andersson, C.D.,Weigelt, J.,Linusson, A.,Elofsson, M.,Schuler, H. (登録日: 2012-08-30, 公開日: 2013-06-19, 最終更新日: 2023-11-08)

主引用文献

Lindgren, A.E.G.,Karlberg, T.,Thorsell, A.G.,Hesse, M.,Spjut, S.,Ekblad, T.,Andersson, C.D.,Pinto, A.F.,Weigelt, J.,Hottiger, M.O.,Linusson, A.,Elofsson, M.,Schuler, H.
PARP Inhibitor with Selectivity Toward ADP-Ribosyltransferase ARTD3/PARP3
Acs Chem.Biol., 8:1698-1703, 2013

PubMed Abstract: Inhibiting ADP-ribosyl transferases with PARP-inhibitors is considered a promising strategy for the treatment of many cancers and ischemia, but most of the cellular targets are poorly characterized. Here, we describe an inhibitor of ADP-ribosyltransferase-3/poly(ADP-ribose) polymerase-3 (ARTD3), a regulator of DNA repair and mitotic progression. In vitro profiling against 12 members of the enzyme family suggests selectivity for ARTD3, and crystal structures illustrate the molecular basis for inhibitor selectivity. The compound is active in cells, where it elicits ARTD3-specific effects at submicromolar concentration. Our results show that by targeting the nicotinamide binding site, selective inhibition can be achieved among the closest relatives of the validated clinical target, ADP-ribosyltransferase-1/poly(ADP-ribose) polymerase-1.

PubMed: 23742272
DOI: 10.1021/cb4002014

実験手法

X-RAY DIFFRACTION (1.8 Å)