1GS0

Crystal structure of the catalytic fragment of murine poly(ADP-ribose) polymerase-2

Summary for 1GS0

• Entry DOI: 10.2210/pdb1gs0/pdb
• Descriptor: POLY (ADP-RIBOSE) POLYMERASE-2 (2 entities in total)
• Functional Keywords: transferase, catalytic fragment, polymerase transferase, nuclear protein, dna-binding
• Biological source: MUS MUSCULUS (MOUSE)
• Cellular location: Nucleus: O88554
• Total number of polymer chains: 2
• Total formula weight: 79395.41

Authors

Oliver, A.W.,Roe, S.M.,Pearl, L.H. (deposition date: 2001-12-19, release date: 2002-12-19, Last modification date: 2023-12-13)

Primary citation

Oliver, A.W.,Ame, J.C.,Roe, S.M.,Good, V.,De Murcia, G.,Pearl, L.H.
Crystal Structure of the Catalytic Fragment of Murine Poly(Adp-Ribose) Polymerase-2
Nucleic Acids Res., 32:456-, 2004

PubMed Abstract: Poly(ADP-ribose) polymerase-1 (PARP-1) has become an important pharmacological target in the treatment of cancer due to its cellular role as a 'DNA-strand break sensor', which leads in part to resistance to some existing chemo- and radiological treatments. Inhibitors have now been developed which prevent PARP-1 from synthesizing poly(ADP-ribose) in response to DNA-breaks and potentiate the cytotoxicity of DNA damaging agents. However, with the recent discoveries of PARP-2, which has a similar DNA-damage dependent catalytic activity, and additional members containing the 'PARP catalytic' signature, the isoform selectivity and resultant pharmacological effects of existing inhibitors are brought into question. We present here the crystal structure of the catalytic fragment of murine PARP-2, at 2.8 A resolution, and compare this to the catalytic fragment of PARP-1, with an emphasis on providing a possible framework for rational drug design in order to develop future isoform-specific inhibitors.

PubMed: 14739238
DOI: 10.1093/NAR/GKH215

Experimental method

X-RAY DIFFRACTION (2.8 Å)