6G0W

Human PARP14 (ARTD8), catalytic fragment in complex with inhibitor MCD72

6G0W の概要

• エントリーDOI: 10.2210/pdb6g0w/pdb
• 分子名称: Poly [ADP-ribose] polymerase 14, 4-[3-[4-(4-fluorophenyl)piperidin-1-yl]carbonylphenoxy]benzamide (3 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)
• 細胞内の位置: Nucleus : Q460N5
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 45074.10

構造登録者

Karlberg, T.,Thorsell, A.G.,Holechek, J.,Lease, R.,Ferraris, D.,Schuler, H. (登録日: 2018-03-20, 公開日: 2018-05-23, 最終更新日: 2024-11-13)

主引用文献

Holechek, J.,Lease, R.,Thorsell, A.G.,Karlberg, T.,McCadden, C.,Grant, R.,Keen, A.,Callahan, E.,Schuler, H.,Ferraris, D.
Design, synthesis and evaluation of potent and selective inhibitors of mono-(ADP-ribosyl)transferases PARP10 and PARP14.
Bioorg. Med. Chem. Lett., 28:2050-2054, 2018

PubMed Abstract: A series of diaryl ethers were designed and synthesized to discern the structure activity relationships against the two closely related mono-(ADP-ribosyl)transferases PARP10 and PARP14. Structure activity studies identified 8b as a sub-micromolar inhibitor of PARP10 with ∼15-fold selectivity over PARP14. In addition, 8k and 8m were discovered to have sub-micromolar potency against PARP14 and demonstrated moderate selectivity over PARP10. A crystal structure of the complex of PARP14 and 8b shows binding of the compound in a novel hydrophobic pocket and explains both potency and selectivity over other PARP family members. In addition, 8b, 8k and 8m also demonstrate selectivity over PARP1. Together, this study identified novel, potent and metabolically stable derivatives to use as chemical probes for these biologically interesting therapeutic targets.

PubMed: 29748053
DOI: 10.1016/j.bmcl.2018.04.056

実験手法

X-RAY DIFFRACTION (2.34 Å)