4EPQ

canonical poly(ADP-ribose) glycohydrolase RBPI inhibitor complex from Tetrahymena thermophila

Summary for 4EPQ

• Entry DOI: 10.2210/pdb4epq/pdb
• Related: 4EPP
• Descriptor: Poly(ADP-ribose) glycohydrolase, 3-{(5Z)-5-[5-chloro-1-(2,6-dichlorobenzyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl}propanoic acid (3 entities in total)
• Functional Keywords: macro domain, par, hydrolase-inhibitor complex, hydrolase/inhibitor
• Biological source: Tetrahymena thermophila
• Total number of polymer chains: 1
• Total formula weight: 56400.86

Authors

Dunstan, M.S.,Leys, D. (deposition date: 2012-04-17, release date: 2012-06-13, Last modification date: 2023-09-13)

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 (2.399 Å)