4RV6
Human ARTD1 (PARP1) catalytic domain in complex with inhibitor Rucaparib
Summary for 4RV6
| Entry DOI | 10.2210/pdb4rv6/pdb |
| Related | 4r5w 4r6e 4und 4uxb |
| Descriptor | Poly [ADP-ribose] polymerase 1, SULFATE ION, Rucaparib, ... (4 entities in total) |
| Functional Keywords | adp-ribosyl transferase, adp-ribosylation, transferase-transferase inhibitor complex, transferase/transferase inhibitor |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 4 |
| Total formula weight | 158771.42 |
| Authors | Karlberg, T.,Thorsell, A.G.,Schuler, H. (deposition date: 2014-11-25, release date: 2015-12-09, Last modification date: 2023-09-20) |
| Primary citation | Thorsell, A.G.,Ekblad, T.,Karlberg, T.,Low, M.,Pinto, A.F.,Tresaugues, L.,Moche, M.,Cohen, M.S.,Schuler, H. Structural Basis for Potency and Promiscuity in Poly(ADP-ribose) Polymerase (PARP) and Tankyrase Inhibitors. J. Med. Chem., 60:1262-1271, 2017 Cited by PubMed Abstract: Selective inhibitors could help unveil the mechanisms by which inhibition of poly(ADP-ribose) polymerases (PARPs) elicits clinical benefits in cancer therapy. We profiled 10 clinical PARP inhibitors and commonly used research tools for their inhibition of multiple PARP enzymes. We also determined crystal structures of these compounds bound to PARP1 or PARP2. Veliparib and niraparib are selective inhibitors of PARP1 and PARP2; olaparib, rucaparib, and talazoparib are more potent inhibitors of PARP1 but are less selective. PJ34 and UPF1069 are broad PARP inhibitors; PJ34 inserts a flexible moiety into hydrophobic subpockets in various ADP-ribosyltransferases. XAV939 is a promiscuous tankyrase inhibitor and a potent inhibitor of PARP1 in vitro and in cells, whereas IWR1 and AZ-6102 are tankyrase selective. Our biochemical and structural analysis of PARP inhibitor potencies establishes a molecular basis for either selectivity or promiscuity and provides a benchmark for experimental design in assessment of PARP inhibitor effects. PubMed: 28001384DOI: 10.1021/acs.jmedchem.6b00990 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.19 Å) |
Structure validation
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