Structure and mechanism of a canonical poly(ADP-ribose) glycohydrolase.
Authors
Dunstan, MBarkauskaite, Eva
Lafite, P
Knezevic, C
Brassington, A
Ahel, Marijan
Hergenrother, P
Leys, D
Ahel, I
Affiliation
Manchester Interdisciplinary Biocentre, Princess Street 131, M1 7DN, Manchester, UK.Issue Date
2012
Metadata
Show full item recordAbstract
Poly(ADP-ribosyl)ation is a reversible post-translational protein modification involved in the regulation of a number of cellular processes including DNA repair, chromatin structure, mitosis, transcription, checkpoint activation, apoptosis and asexual development. The reversion of poly(ADP-ribosyl)ation is catalysed by poly(ADP-ribose) (PAR) glycohydrolase (PARG), which specifically targets the unique PAR (1''-2') ribose-ribose bonds. Here we report the structure and mechanism of the first canonical PARG from the protozoan Tetrahymena thermophila. In addition, we reveal the structure of T. thermophila PARG in a complex with a novel rhodanine-containing mammalian PARG inhibitor RBPI-3. Our data demonstrate that the protozoan PARG represents a good model for human PARG and is therefore likely to prove useful in guiding structure-based discovery of new classes of PARG inhibitors.Citation
Structure and mechanism of a canonical poly(ADP-ribose) glycohydrolase. 2012, 3:878 Nat CommunJournal
Nature CommunicationsDOI
10.1038/ncomms1889PubMed ID
22673905Type
ArticleLanguage
enISSN
2041-1723ae974a485f413a2113503eed53cd6c53
10.1038/ncomms1889