4EPP

Canonical poly(ADP-ribose) glycohydrolase from Tetrahymena thermophila.

Summary for 4EPP

• Entry DOI: 10.2210/pdb4epp/pdb
• Related: 4EPQ
• Descriptor: Poly(ADP-ribose) glycohydrolase, ADENOSINE-5-DIPHOSPHORIBOSE (3 entities in total)
• Functional Keywords: marco domain, par, hydrolase
• Biological source: Tetrahymena thermophila
• Total number of polymer chains: 2
• Total formula weight: 112890.69

Authors

Dunstan, M.S.,Leys, D. (deposition date: 2012-04-17, release date: 2012-06-20, Last modification date: 2024-02-28)

Primary citation

Dunstan, M.S.,Barkauskaite, E.,Lafite, P.,Knezevic, C.E.,Brassington, A.,Ahel, M.,Hergenrother, P.J.,Leys, D.,Ahel, I.
Structure and mechanism of a canonical poly(ADP-ribose) glycohydrolase.
Nat Commun, 3:878-878, 2012

PubMed 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.

PubMed: 22673905
DOI: 10.1038/ncomms1889

Experimental method

X-RAY DIFFRACTION (1.95 Å)