title: Structure of mammalian poly(ADP-ribose) glycohydrolase reveals a flexible tyrosine clasp as a substrate-binding element.
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.
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: In-Kwon
authors.initials: IK
authors.lastname: Kim
authors.forename: James R
authors.initials: JR
authors.lastname: Kiefer
authors.forename: Chris M W
authors.initials: CM
authors.lastname: Ho
authors.forename: Roderick A
authors.initials: RA
authors.lastname: Stegeman
authors.forename: Scott
authors.initials: S
authors.lastname: Classen
authors.forename: John A
authors.initials: JA
authors.lastname: Tainer
authors.forename: Tom
authors.initials: T
authors.lastname: Ellenberger
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D006026:Glycoside Hydrolases / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D051381:Rats; D016415:Sequence Alignment
chemical_list: D006026:Glycoside Hydrolases; C022407:poly ADP-ribose glycohydrolase