4F0E

Human ADP-RIBOSYLTRANSFERASE 7 (ARTD7/PARP15), CATALYTIC DOMAIN IN COMPLEX WITH STO1102

4F0E の概要

• エントリーDOI: 10.2210/pdb4f0e/pdb
• 関連するPDBエントリー: 3BLJ 3GEY
• 分子名称: Poly [ADP-ribose] polymerase 15, 8-methyl-2-[(pyrimidin-2-ylsulfanyl)methyl]quinazolin-4(1H)-one (3 entities in total)
• 機能のキーワード: artd, parp, poly (adp-ribose) polymerase, adp-ribose, bal3, b-aggressive lymphoma protein 3, transferase, glycosyltransferase, nucleus, transcription, transcription regulation, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus (Probable): Q460N3
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 92724.15

構造登録者

Karlberg, T.,Andersson, C.D.,Lindgren, A.,Thorsell, A.G.,Ekblad, T.,Spjut, S.,Weigelt, J.,Elofsson, M.,Linusson, A.,Schuler, H. (登録日: 2012-05-04, 公開日: 2012-09-05, 最終更新日: 2024-05-29)

主引用文献

Andersson, C.D.,Karlberg, T.,Ekblad, T.,Lindgren, A.E.,Thorsell, A.G.,Spjut, S.,Uciechowska, U.,Niemiec, M.S.,Wittung-Stafshede, P.,Weigelt, J.,Elofsson, M.,Schuler, H.,Linusson, A.
Discovery of Ligands for ADP-Ribosyltransferases via Docking-Based Virtual Screening.
J.Med.Chem., 55:7706-7718, 2012

PubMed Abstract: The diphtheria toxin-like ADP-ribosyltransferases (ARTDs) are an enzyme family that catalyzes the transfer of ADP-ribose units onto substrate proteins by using nicotinamide adenine dinucleotide (NAD(+)) as a cosubstrate. They have a documented role in chromatin remodelling and DNA repair, and inhibitors of ARTD1 and 2 (PARP1 and 2) are currently in clinical trials for the treatment of cancer. The detailed function of most other ARTDs is still unknown. By using virtual screening, we identified small ligands of ARTD7 (PARP15/BAL3) and ARTD8 (PARP14/BAL2). Thermal-shift assays confirmed that 16 compounds, belonging to eight structural classes, bound to ARTD7/ARTD8. Affinity measurements with isothermal titration calorimetry for two isomers of the most promising hit compound confirmed binding in the low micromolar range to ARTD8. Crystal structures showed anchoring of the hits in the nicotinamide pocket. These results form a starting point in the development of chemical tools for the study of the role and function of ARTD7 and ARTD8.

PubMed: 22823910
DOI: 10.1021/jm300746d

実験手法

X-RAY DIFFRACTION (2.4 Å)