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PDBsum entry 4l2h
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References listed in PDB file
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Key reference
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Title
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Visualization of poly(ADP-Ribose) bound to parg reveals inherent balance between exo- And endo-Glycohydrolase activities.
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Authors
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E.Barkauskaite,
A.Brassington,
E.S.Tan,
J.Warwicker,
M.S.Dunstan,
B.Banos,
P.Lafite,
M.Ahel,
T.J.Mitchison,
I.Ahel,
D.Leys.
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Ref.
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Nat Commun, 2013,
4,
2164.
[DOI no: ]
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PubMed id
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Abstract
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Poly-ADP-ribosylation is a post-translational modification that regulates
processes involved in genome stability. Breakdown of the poly(ADP-ribose) (PAR)
polymer is catalysed by poly(ADP-ribose) glycohydrolase (PARG), whose
endo-glycohydrolase activity generates PAR fragments. Here we present the
crystal structure of PARG incorporating the PAR substrate. The two terminal
ADP-ribose units of the polymeric substrate are bound in exo-mode. Biochemical
and modelling studies reveal that PARG acts predominantly as an
exo-glycohydrolase. This preference is linked to Phe902 (human numbering), which
is responsible for low-affinity binding of the substrate in endo-mode. Our data
reveal the mechanism of poly-ADP-ribosylation reversal, with ADP-ribose as the
dominant product, and suggest that the release of apoptotic PAR fragments occurs
at unusual PAR/PARG ratios.
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