4AVU
Crystal structure of human tankyrase 2 in complex with 6(5H)- phenanthridinone
Summary for 4AVU
| Entry DOI | 10.2210/pdb4avu/pdb |
| Related | 2Y0I |
| Descriptor | TANKYRASE-2, ZINC ION, SULFATE ION, ... (7 entities in total) |
| Functional Keywords | transferase, diphtheria toxin like fold, adp- ribosylation, transferase-transferase inhibitor complex |
| Biological source | HOMO SAPIENS (HUMAN) |
| Total number of polymer chains | 2 |
| Total formula weight | 55901.46 |
| Authors | Haikarainen, T.,Narwal, M.,Lehtio, L. (deposition date: 2012-05-29, release date: 2012-06-13, Last modification date: 2024-05-08) |
| Primary citation | Haikarainen, T.,Narwal, M.,Joensuu, P.,Lehtio, L. Evaluation and Structural Basis for the Inhibition of Tankyrases by Parp Inhibitors Acs Med.Chem.Lett., 5:18-, 2014 Cited by PubMed Abstract: Tankyrases, an enzyme subfamily of human poly(ADP-ribosyl)polymerases, are potential drug targets especially against cancer. We have evaluated inhibition of tankyrases by known PARP inhibitors and report five cocrystal structures of the most potent compounds in complex with human tankyrase 2. The inhibitors include the small general PARP inhibitors Phenanthridinone, PJ-34, and TIQ-A as well as the more advanced inhibitors EB-47 and rucaparib. The compounds anchor to the nicotinamide subsite of tankyrase 2. Crystal structures reveal flexibility of the ligand binding site with implications for drug development against tankyrases and other ADP-ribosyltransferases. EB-47 mimics the substrate NAD(+) and extends from the nicotinamide to the adenosine subsite. The clinical ARTD1 inhibitor candidate rucaparib was the most potent tankyrase inhibitor identified (24 and 14 nM for tankyrases), which indicates that inhibition of tankyrases would affect the cellular responses of this compound. PubMed: 24900770DOI: 10.1021/ML400292S PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.4 Å) |
Structure validation
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