Publication
Article Metrics
Citations
Online attention
Structure and mechanism of a canonical poly(ADP-ribose) glycohydrolase
DOI:
10.1038/ncomms1889
PMID:
22673905
Authors:
Mark
Dunstan
(University of Manchester)
,
Eva
Barkauskaite
(University of Oxford)
,
Pierre
Lafite
(Université d'Orléans)
,
Claire E.
Knezevic
(University of Illinois at Urbana-Champaign)
,
Amy
Brassington
(Manchester Interdisciplinary Biocentre)
,
Marijan
Ahel
(Rudjer Boskovic Institute, Zagreb, Croatia)
,
Paul J.
Hergenrother
(University of Illinois at Urbana-Champaign)
,
David
Leys
(School of Chemistry & Manchester Interdisciplinary Biocentre, The University of Manchester)
,
Ivan
Ahel
(Paterson Institute for Cancer Research, University of Manchester,)
Co-authored by industrial partner:
No
Type:
Journal Paper
Journal:
Nature Communications
, VOL 3 (878)
, PAGES 3 (878)
State:
Published (Approved)
Published:
June 2012
Diamond Proposal Number(s):
7146
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.
Journal Keywords: Humans; Phylogeny; Protein; Secondary; Protein; Tertiary; Tetrahymena thermophila
Subject Areas:
Biology and Bio-materials,
Medicine,
Chemistry
Instruments:
I04-Macromolecular Crystallography