6VKO
Crystal Structure of human PARP-1 CAT domain bound to inhibitor UKTT15
Summary for 6VKO
| Entry DOI | 10.2210/pdb6vko/pdb |
| Descriptor | Poly [ADP-ribose] polymerase 1, methyl 2-{4-[4-(7-carbamoyl-1H-benzimidazol-2-yl)benzene-1-carbonyl]piperazin-1-yl}pyrimidine-5-carboxylate, SULFATE ION, ... (4 entities in total) |
| Functional Keywords | parp-1, poly(adp-ribose) polymerase, parp inhibitor, parp1, artd1, transferase, transferase-inhibitor complex, transferase/inhibitor |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 4 |
| Total formula weight | 169384.58 |
| Authors | Langelier, M.F.,Pascal, J.M. (deposition date: 2020-01-21, release date: 2020-06-17, Last modification date: 2024-11-13) |
| Primary citation | Zandarashvili, L.,Langelier, M.F.,Velagapudi, U.K.,Hancock, M.A.,Steffen, J.D.,Billur, R.,Hannan, Z.M.,Wicks, A.J.,Krastev, D.B.,Pettitt, S.J.,Lord, C.J.,Talele, T.T.,Pascal, J.M.,Black, B.E. Structural basis for allosteric PARP-1 retention on DNA breaks. Science, 368:-, 2020 Cited by PubMed Abstract: The success of poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors (PARPi) to treat cancer relates to their ability to trap PARP-1 at the site of a DNA break. Although different forms of PARPi all target the catalytic center of the enzyme, they have variable abilities to trap PARP-1. We found that several structurally distinct PARPi drive PARP-1 allostery to promote release from a DNA break. Other inhibitors drive allostery to retain PARP-1 on a DNA break. Further, we generated a new PARPi compound, converting an allosteric pro-release compound to a pro-retention compound and increasing its ability to kill cancer cells. These developments are pertinent to clinical applications where PARP-1 trapping is either desirable or undesirable. PubMed: 32241924DOI: 10.1126/science.aax6367 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.8 Å) |
Structure validation
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