3KJD

Human poly(ADP-ribose) polymerase 2, catalytic fragment in complex with an inhibitor ABT-888

Summary for 3KJD

• Entry DOI: 10.2210/pdb3kjd/pdb
• Related: 3KCZ
• Descriptor: Poly [ADP-ribose] polymerase 2, (2R)-2-(7-carbamoyl-1H-benzimidazol-2-yl)-2-methylpyrrolidinium, GLYCEROL, ... (4 entities in total)
• Functional Keywords: transferase, enzyme-inhibitor complex, catalytic fragment, structural genomics, structural genomics consortium, sgc, glycosyltransferase, nad, nucleus, dna-binding
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: Q9UGN5
• Total number of polymer chains: 2
• Total formula weight: 84328.62

Authors

Karlberg, T.,Schutz, P.,Arrowsmith, C.H.,Berglund, H.,Bountra, C.,Collins, R.,Edwards, A.M.,Flodin, S.,Flores, A.,Graslund, S.,Hammarstrom, M.,Johansson, A.,Johansson, I.,Kallas, A.,Kotenyova, T.,Kotzsch, A.,Kraulis, P.,Nielsen, T.K.,Moche, M.,Nordlund, P.,Nyman, T.,Persson, C.,Roos, A.K.,Siponen, M.I.,Thorsell, A.G.,Tresaugues, L.,Van Den Berg, S.,Weigelt, J.,Welin, M.,Wisniewska, M.,Schuler, H.,Structural Genomics Consortium (SGC) (deposition date: 2009-11-03, release date: 2009-11-17, Last modification date: 2023-11-01)

Primary citation

Karlberg, T.,Hammarstrom, M.,Schutz, P.,Svensson, L.,Schuler, H.
Crystal structure of the catalytic domain of human PARP2 in complex with PARP inhibitor ABT-888.
Biochemistry, 49:1056-1058, 2010

PubMed Abstract: 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.

PubMed: 20092359
DOI: 10.1021/bi902079y

Experimental method

X-RAY DIFFRACTION (1.95 Å)