| Literature DB >> 22673905 |
Mark S Dunstan1, Eva Barkauskaite, Pierre Lafite, Claire E Knezevic, Amy Brassington, Marijan Ahel, Paul J Hergenrother, David Leys, Ivan Ahel.
Abstract
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.Entities:
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Year: 2012 PMID： 22673905 DOI： 10.1038/ncomms1889
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919