Structure of mammalian poly(ADP-ribose) glycohydrolase reveals a flexible tyrosine clasp as a substrate-binding element

In Kwon Kim, James R. Kiefer, Chris M.W. Ho, Roderick A. Stegeman, Scott Classen, John A. Tainer, Tom Ellenberger

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)653-656
Number of pages4
JournalNature Structural and Molecular Biology
Volume19
Issue number6
DOIs
StatePublished - Jun 2012

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