4N9Z

Crystal structure of mouse poly(ADP-ribose) glycohydrolase (PARG) catalytic domain mutant E749Q

Summary for 4N9Z

• Entry DOI: 10.2210/pdb4n9z/pdb
• Related: 4FC2 4N9Y 4NA0 4NA4 4NA5 4NA6
• Descriptor: Poly(ADP-ribose) glycohydrolase, 2'-O-(5-O-phosphono-alpha-D-ribofuranosyl)adenosine 5'-(dihydrogen phosphate), SULFATE ION, ... (4 entities in total)
• Functional Keywords: poly(adp-ribose) glycohydrolase, parg, hydrolase
• Biological source: Mus musculus (mouse)
• Cellular location: Nucleus (By similarity): O88622
• Total number of polymer chains: 2
• Total formula weight: 122372.46

Authors

Wang, Z.,Cheng, Z.,Xu, W. (deposition date: 2013-10-21, release date: 2014-01-29, Last modification date: 2023-09-20)

Primary citation

Wang, Z.,Gagne, J.P.,Poirier, G.G.,Xu, W.
Crystallographic and biochemical analysis of the mouse poly(ADP-ribose) glycohydrolase.
Plos One, 9:e86010-e86010, 2014

PubMed Abstract: Protein poly(ADP-ribosyl)ation (PARylation) regulates a number of important cellular processes. Poly(ADP-ribose) glycohydrolase (PARG) is the primary enzyme responsible for hydrolyzing the poly(ADP-ribose) (PAR) polymer in vivo. Here we report crystal structures of the mouse PARG (mPARG) catalytic domain, its complexes with ADP-ribose (ADPr) and a PARG inhibitor ADP-HPD, as well as four PARG catalytic residues mutants. With these structures and biochemical analysis of 20 mPARG mutants, we provide a structural basis for understanding how the PAR polymer is recognized and hydrolyzed by mPARG. The structures and activity complementation experiment also suggest how the N-terminal flexible peptide preceding the PARG catalytic domain may regulate the enzymatic activity of PARG. This study contributes to our understanding of PARG catalytic and regulatory mechanisms as well as the rational design of PARG inhibitors.

PubMed: 24465839
DOI: 10.1371/journal.pone.0086010

Experimental method

X-RAY DIFFRACTION (1.9 Å)