Crystal structure of the catalytic domain of human PARP2 in complex with PARP inhibitor ABT-888

Biochemistry. 2010 Feb 16;49(6):1056-8. doi: 10.1021/bi902079y.


Poly-ADP-ribose polymerases (PARPs) catalyze transfer of ADP-ribose from NAD(+) to specific residues in their substrate proteins or to growing ADP-ribose chains. PARP activity is involved in processes such as chromatin remodeling, transcription control, and DNA repair. Inhibitors of PARP activity may be useful in cancer therapy. PARP2 is the family member that is most similar to PARP1, and the two can act together as heterodimers. We used X-ray crystallography to determine two structures of the catalytic domain of human PARP2: the complexes with PARP inhibitors 3-aminobenzamide and ABT-888. These results contribute to our understanding of structural features and compound properties that can be employed to develop selective inhibitors of human ADP-ribosyltransferases.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzamides / chemistry
  • Benzimidazoles / chemistry*
  • Catalytic Domain* / drug effects
  • Cell Cycle Proteins / chemistry
  • Crystallization
  • Crystallography, X-Ray
  • Glutamic Acid / chemistry
  • Humans
  • Hydrogen Bonding / drug effects
  • Mice
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerase Inhibitors*
  • Poly(ADP-ribose) Polymerases / chemistry*
  • Protein Structure, Secondary / drug effects


  • Benzamides
  • Benzimidazoles
  • Cell Cycle Proteins
  • Poly(ADP-ribose) Polymerase Inhibitors
  • veliparib
  • Glutamic Acid
  • 3-aminobenzamide
  • PARP1 protein, human
  • PARP2 protein, human
  • PARP3 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases

Associated data

  • PDB/1GS0
  • PDB/2RD6
  • PDB/3C4H
  • PDB/3KCZ
  • PDB/3KJD