Summary for 7OMC
| Entry DOI | 10.2210/pdb7omc/pdb |
| Descriptor | Poly [ADP-ribose] polymerase tankyrase-2, 8-propan-2-yloxy-4~{H}-thieno[2,3-c]isoquinolin-5-one, ZINC ION, ... (7 entities in total) |
| Functional Keywords | inhibitor, enzyme, transferase |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 50817.99 |
| Authors | Sowa, S.T.,Lehtio, L. (deposition date: 2021-05-21, release date: 2021-12-08, Last modification date: 2024-01-31) |
| Primary citation | Maksimainen, M.M.,Murthy, S.,Sowa, S.T.,Galera-Prat, A.,Rolina, E.,Heiskanen, J.P.,Lehtio, L. Analogs of TIQ-A as inhibitors of human mono-ADP-ribosylating PARPs. Bioorg.Med.Chem., 52:116511-116511, 2021 Cited by PubMed Abstract: The scaffold of TIQ-A, a previously known inhibitor of human poly-ADP-ribosyltransferase PARP1, was utilized to develop inhibitors against human mono-ADP-ribosyltransferases through structure-guided design and activity profiling. By supplementing the TIQ-A scaffold with small structural changes, based on a PARP10 inhibitor OUL35, selectivity changed from poly-ADP-ribosyltransferases towards mono-ADP-ribosyltransferases. Binding modes of analogs were experimentally verified by determining complex crystal structures with mono-ADP-ribosyltransferase PARP15 and with poly-ADP-ribosyltransferase TNKS2. The best analogs of the study achieved 10-20-fold selectivity towards mono-ADP-ribosyltransferases PARP10 and PARP15 while maintaining micromolar potencies. The work demonstrates a route to differentiate compound selectivity between mono- and poly-ribosyltransferases of the human ARTD family. PubMed: 34801828DOI: 10.1016/j.bmc.2021.116511 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
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