4GV7
Human ARTD1 (PARP1) - Catalytic domain in complex with inhibitor ME0328
Summary for 4GV7
| Entry DOI | 10.2210/pdb4gv7/pdb |
| Descriptor | Poly [ADP-ribose] polymerase 1, 2-methylquinazolin-4(3H)-one (2 entities in total) |
| Functional Keywords | nad, adp-ribose, parp1, artd1, artd transferase domain, adp-ribosylation, transferase-transferase inhibitor complex, adp-ribose transferase, transferase/transferase inhibitor |
| Biological source | Homo sapiens (human) |
| Cellular location | Nucleus: P09874 |
| Total number of polymer chains | 4 |
| Total formula weight | 161440.49 |
| Authors | Karlberg, T.,Thorsell, A.G.,Lindgren, A.E.G.,Ekblad, T.,Spjut, S.,Andersson, C.D.,Weigelt, J.,Linusson, A.,Elofsson, M.,Schuler, H. (deposition date: 2012-08-30, release date: 2013-06-19, Last modification date: 2023-11-08) |
| Primary citation | Lindgren, A.E.G.,Karlberg, T.,Thorsell, A.G.,Hesse, M.,Spjut, S.,Ekblad, T.,Andersson, C.D.,Pinto, A.F.,Weigelt, J.,Hottiger, M.O.,Linusson, A.,Elofsson, M.,Schuler, H. PARP Inhibitor with Selectivity Toward ADP-Ribosyltransferase ARTD3/PARP3 Acs Chem.Biol., 8:1698-1703, 2013 Cited by PubMed Abstract: Inhibiting ADP-ribosyl transferases with PARP-inhibitors is considered a promising strategy for the treatment of many cancers and ischemia, but most of the cellular targets are poorly characterized. Here, we describe an inhibitor of ADP-ribosyltransferase-3/poly(ADP-ribose) polymerase-3 (ARTD3), a regulator of DNA repair and mitotic progression. In vitro profiling against 12 members of the enzyme family suggests selectivity for ARTD3, and crystal structures illustrate the molecular basis for inhibitor selectivity. The compound is active in cells, where it elicits ARTD3-specific effects at submicromolar concentration. Our results show that by targeting the nicotinamide binding site, selective inhibition can be achieved among the closest relatives of the validated clinical target, ADP-ribosyltransferase-1/poly(ADP-ribose) polymerase-1. PubMed: 23742272DOI: 10.1021/cb4002014 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.89 Å) |
Structure validation
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