4F0E
Human ADP-RIBOSYLTRANSFERASE 7 (ARTD7/PARP15), CATALYTIC DOMAIN IN COMPLEX WITH STO1102
Summary for 4F0E
| Entry DOI | 10.2210/pdb4f0e/pdb |
| Related | 3BLJ 3GEY |
| Descriptor | Poly [ADP-ribose] polymerase 15, 8-methyl-2-[(pyrimidin-2-ylsulfanyl)methyl]quinazolin-4(1H)-one (3 entities in total) |
| Functional Keywords | 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 |
| Biological source | Homo sapiens (human) |
| Cellular location | Nucleus (Probable): Q460N3 |
| Total number of polymer chains | 4 |
| Total formula weight | 92724.15 |
| Authors | Karlberg, T.,Andersson, C.D.,Lindgren, A.,Thorsell, A.G.,Ekblad, T.,Spjut, S.,Weigelt, J.,Elofsson, M.,Linusson, A.,Schuler, H. (deposition date: 2012-05-04, release date: 2012-09-05, Last modification date: 2024-05-29) |
| Primary citation | 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 Cited by 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: 22823910DOI: 10.1021/jm300746d PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.4 Å) |
Structure validation
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