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Structure and mechanism of a canonical poly(ADP-ribose) glycohydrolase.

dc.contributor.authorDunstan, M
dc.contributor.authorBarkauskaite, Eva
dc.contributor.authorLafite, P
dc.contributor.authorKnezevic, C
dc.contributor.authorBrassington, A
dc.contributor.authorAhel, Marijan
dc.contributor.authorHergenrother, P
dc.contributor.authorLeys, D
dc.contributor.authorAhel, I
dc.date.accessioned2012-12-05T17:10:08Z
dc.date.available2012-12-05T17:10:08Z
dc.date.issued2012
dc.identifier.citationStructure and mechanism of a canonical poly(ADP-ribose) glycohydrolase. 2012, 3:878 Nat Communen_GB
dc.identifier.issn2041-1723
dc.identifier.pmid22673905
dc.identifier.doi10.1038/ncomms1889
dc.identifier.urihttp://hdl.handle.net/10541/254630
dc.description.abstractPoly(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.
dc.language.isoenen
dc.rightsArchived with thanks to Nature communicationsen_GB
dc.subject.meshGlycoside Hydrolases
dc.subject.meshHumans
dc.subject.meshPhylogeny
dc.subject.meshProtein Structure, Secondary
dc.subject.meshProtein Structure, Tertiary
dc.subject.meshTetrahymena thermophila
dc.titleStructure and mechanism of a canonical poly(ADP-ribose) glycohydrolase.en
dc.typeArticleen
dc.contributor.departmentManchester Interdisciplinary Biocentre, Princess Street 131, M1 7DN, Manchester, UK.en_GB
dc.identifier.journalNature Communicationsen_GB
html.description.abstractPoly(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.


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