Structure of mammalian poly(ADP-ribose) glycohydrolase

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Poly ADP-ribosylation regulates cellular processes such as genomic stability maintenance, transcription and cell death. The structure of rat poly(ADP-ribose) glycohydrolase has been determined using crystallographic data collected at the SIBYLS beamline, giving insights into the enzyme’s endoglycosidase activity and providing a basis for the development of therapeutic inhibitors.


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Reversible post-translational modification by poly(ADP-ribose) (PAR) regulates chromatin structure, DNA repair and cell fate in response to genotoxic stress. PAR glycohydrolase (PARG) removes PAR chains from poly ADP-ribosylated proteins to restore protein function and release oligo(ADP-ribose) chains to signal damage. Here we report crystal structures of mammalian PARG and its complex with a substrate mimic that reveal an open substrate-binding site and a unique ‘tyrosine clasp’ enabling endoglycosidic cleavage of branched PAR chains.


Kim, I.-K., Kiefer, J.R., Ho, C.M.W., Stegeman, R.A., Classen, S., Tainer, J.A., and Ellenberger, T. “Structure of mammalian poly(ADP-ribose) glycohydrolase reveals a flexible tyrosine clasp as a substrate-binding element.” Nat Struct Mol Biol. (May 2012)

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