Structure and mechanism of a canonical poly(ADP-ribose) glycohydrolase.
AffiliationManchester Interdisciplinary Biocentre, Princess Street 131, M1 7DN, Manchester, UK.
MetadataShow full item record
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.
CitationStructure and mechanism of a canonical poly(ADP-ribose) glycohydrolase. 2012, 3:878 Nat Commun
- The structure and catalytic mechanism of a poly(ADP-ribose) glycohydrolase.
- Authors: Slade D, Dunstan MS, Barkauskaite E, Weston R, Lafite P, Dixon N, Ahel M, Leys D, Ahel I
- Issue date: 2011 Sep 4
- Visualization of poly(ADP-ribose) bound to PARG reveals inherent balance between exo- and endo-glycohydrolase activities.
- Authors: Barkauskaite E, Brassington A, Tan ES, Warwicker J, Dunstan MS, Banos B, Lafite P, Ahel M, Mitchison TJ, Ahel I, Leys D
- Issue date: 2013
- Targeting poly(ADP-ribose) glycohydrolase to draw apoptosis codes in cancer.
- Authors: Tanuma SI, Shibui Y, Oyama T, Uchiumi F, Abe H
- Issue date: 2019 Sep
- Functional Role of ADP-Ribosyl-Acceptor Hydrolase 3 in poly(ADP-Ribose) Polymerase-1 Response to Oxidative Stress.
- Authors: Mashimo M, Moss J
- Issue date: 2016
- Roles of poly(ADP-ribose) glycohydrolase in DNA damage and apoptosis.
- Authors: Feng X, Koh DW
- Issue date: 2013