5ADQ
Crystal structure of human tankyrase 2 in complex with JW55
Summary for 5ADQ
| Entry DOI | 10.2210/pdb5adq/pdb |
| Related | 5ADR 5ADS 5ADT |
| Descriptor | TANKYRASE-2, ZINC ION, SULFATE ION, ... (8 entities in total) |
| Functional Keywords | transferase, protein-ligand complex, diphtheria toxin like fold, adp- ribosylation, transferase-transferase inhibitor complex |
| Biological source | HOMO SAPIENS (HUMAN) More |
| Cellular location | Cytoplasm: Q9H2K2 Q9H2K2 |
| Total number of polymer chains | 2 |
| Total formula weight | 28033.71 |
| Authors | Haikarainen, T.,Lehtio, L. (deposition date: 2015-08-24, release date: 2016-01-13, Last modification date: 2024-01-10) |
| Primary citation | Haikarainen, T.,Waaler, J.,Ignatev, A.,Nkizinkiko, Y.,Venkannagari, H.,Obaji, E.,Krauss, S.,Lehtio, L. Development and Structural Analysis of Adenosine Site Binding Tankyrase Inhibitors. Bioorg.Med.Chem.Lett., 26:328-, 2016 Cited by PubMed Abstract: Tankyrases 1 and 2, the specialized members of the ARTD protein family, are druggable biotargets whose inhibition may have therapeutic potential against cancer, metabolic disease, fibrotic disease, fibrotic wound healing and HSV viral infections. We have previously identified a novel tankyrase inhibitor scaffold, JW55, and showed that it reduces mouse colon adenoma formation in vivo. Here we expanded the scaffold and profiled the selectivity of the compounds against a panel of human ARTDs. The scaffold also enables a fine modulation of selectivity towards either tankyrase 1 or tankyrase 2. In order to get insight about the binding mode of the inhibitors, we solved crystal structures of the compounds in complex with tankyrase 2. The compounds bind to the adenosine pocket of the catalytic domain and cause changes in the protein structure that are modulated by the chemical modifications of the compounds. The structural analysis allows further rational development of this compound class as a potent and selective tankyrase inhibitor. PubMed: 26706174DOI: 10.1016/J.BMCL.2015.12.018 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
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