3P0Q

Human Tankyrase 2 - Catalytic PARP domain in complex with an inhibitor

3P0Q の概要

• エントリーDOI: 10.2210/pdb3p0q/pdb
• 関連するPDBエントリー: 3KR7 3P0N 3P0P
• 分子名称: Tankyrase-2, ZINC ION, N-[2-(4-chlorophenyl)ethyl]-6-methyl[1,2,4]triazolo[4,3-b]pyridazin-8-amine, ... (6 entities in total)
• 機能のキーワード: protein-ligand complex, structural genomics, structural genomics consortium, sgc, diphtheria toxin like fold, transferase, nad+, adp-ribosylation, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: Q9H2K2
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 55736.07

構造登録者

Karlberg, T.,Siponen, M.I.,Arrowsmith, C.H.,Berglund, H.,Bountra, C.,Collins, R.,Edwards, A.M.,Flodin, S.,Flores, A.,Graslund, S.,Hammarstrom, M.,Johansson, I.,Kotenyova, T.,Kouznetsova, E.,Moche, M.,Nordlund, P.,Nyman, T.,Persson, C.,Schutz, P.,Sehic, A.,Thorsell, A.G.,Tresaugues, L.,Van Den Berg, S.,Wahlberg, E.,Weigelt, J.,Welin, M.,Schuler, H.,Structural Genomics Consortium (SGC) (登録日: 2010-09-29, 公開日: 2010-10-20, 最終更新日: 2023-11-01)

主引用文献

Wahlberg, E.,Karlberg, T.,Kouznetsova, E.,Markova, N.,Macchiarulo, A.,Thorsell, A.G.,Pol, E.,Frostell, A.,Ekblad, T.,Kull, B.,Robertson, G.M.,Pellicciari, R.,Schuler, H.,Weigelt, J.
Family-wide chemical profiling and structural analysis of PARP and tankyrase inhibitors
Nat.Biotechnol., 30:283-288, 2012

PubMed Abstract: Inhibitors of poly-ADP-ribose polymerase (PARP) family proteins are currently in clinical trials as cancer therapeutics, yet the specificity of many of these compounds is unknown. Here we evaluated a series of 185 small-molecule inhibitors, including research reagents and compounds being tested clinically, for the ability to bind to the catalytic domains of 13 of the 17 human PARP family members including the tankyrases, TNKS1 and TNKS2. Many of the best-known inhibitors, including TIQ-A, 6(5H)-phenanthridinone, olaparib, ABT-888 and rucaparib, bound to several PARP family members, suggesting that these molecules lack specificity and have promiscuous inhibitory activity. We also determined X-ray crystal structures for five TNKS2 ligand complexes and four PARP14 ligand complexes. In addition to showing that the majority of PARP inhibitors bind multiple targets, these results provide insight into the design of new inhibitors.

PubMed: 22343925
DOI: 10.1038/nbt.2121

実験手法

X-RAY DIFFRACTION (1.9 Å)