Paper Citing NAMD - Abstract
Dunstan, Mark S.; Barkauskaite, Eva; Lafite, Pierre; Knezevic, Claire E.; Brassington, Amy; Ahel, Marijan; Hergenrother, Paul J.; Leys, David; Ahel, Ivan
Structure and mechanism of a canonical poly(ADP-ribose) glycohydrolase
NATURE COMMUNICATIONS, 3 Art. No. 878, JUN 2012
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.
