Nucl._Acids_Res.-2004-Oliver-456-64.pdf (457.42 kB)
Crystal structure of the catalytic fragment of murine poly(ADP-ribose) polymerase-2.
journal contribution
posted on 2023-06-08, 08:02 authored by Antony OliverAntony Oliver, J C Amé, S M Roe, V Good, G de Murcia, Laurence PearlLaurence PearlPoly(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.
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Publication status
- Published
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- Published version
Journal
Nucleic Acids ResearchISSN
0305-1048Publisher
Oxford University PressPublisher URL
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2Volume
32Page range
456-464Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2012-02-06First Open Access (FOA) Date
2016-03-22First Compliant Deposit (FCD) Date
2016-11-10Usage metrics
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