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Literature summary for 3.2.1.143 extracted from

  • Wang, Z.; Gagne, J.P.; Poirier, G.G.; Xu, W.
    Crystallographic and biochemical analysis of the mouse poly(ADP-ribose) glycohydrolase (2014), PLoS ONE, 9, e86010.
    View publication on PubMedView publication on EuropePMC

Activating Compound

Activating Compound Comment Organism Structure
additional information the N-terminal regulatory fragment can activate in trans the inactive enzyme fragment depleted with this segment. This suggests that, whereas the enzyme activity can be inhibited by disrupting the docking of this segment to its enzyme binding groove (via posttranslational modification or protein-proteins interactions), the enzyme can be reversibly activated once the disruptive factor is removed Mus musculus

Application

Application Comment Organism
drug development the enzyme is a target for development of specific inhibitors Mus musculus

Crystallization (Commentary)

Crystallization (Comment) Organism
enzyme catalytic domain free or in complexes with ADP-ribose and inhibitor ADP-HPD, as well as four enzyme catalytic residues mutants, X-ray diffraction structure determination and analysis Mus musculus

Protein Variants

Protein Variants Comment Organism
E748N site-directed mutagenesis, the mutant is inactive, activity is disrupted due to significant conformational changes Mus musculus
E748Q site-directed mutagenesis, the mutant activity is highly reduced compared to the wild-type enzyme Mus musculus
E749N site-directed mutagenesis, the mutant is inactive, activity is disrupted due to significant conformational changes Mus musculus
E749Q site-directed mutagenesis, the mutant activity is highly reduced compared to the wild-type enzyme Mus musculus
F868A site-directed mutagenesis, the mutant activity is reduced compared to the wild-type enzyme Mus musculus
G737A/G738A site-directed mutagenesis, the mutant activity is reduced compared to the wild-type enzyme Mus musculus
G866A site-directed mutagenesis, the mutant activity is reduced compared to the wild-type enzyme Mus musculus

Inhibitors

Inhibitors Comment Organism Structure
adenosine 5'-diphosphate-(hydroxymethyl)-pyrrolidinediol ADP-HPD, an analogue of ADP-ribose Mus musculus
additional information the N-terminal regulatory fragment can activate in trans the inactive enzyme fragment depleted with this segment. This suggests that, whereas the enzyme activity can be inhibited by disrupting the docking of this segment to its enzyme binding groove (via posttranslational modification or protein-proteins interactions), the enzyme can be reversibly activated once the disruptive factor is removed Mus musculus

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
poly(ADP-D-ribose)n + H2O Mus musculus
-
poly(ADP-D-ribose)n-1 + ADP-ribose
-
?

Organism

Organism UniProt Comment Textmining
Mus musculus O88622
-
-

Reaction

Reaction Comment Organism Reaction ID
(ADP-ribose)n + H2O = (ADP-ribose)n-1 + ADP-ribose catalytic mechanism, structure-function analysis, overview Mus musculus

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
poly(ADP-D-ribose)n + H2O
-
Mus musculus poly(ADP-D-ribose)n-1 + ADP-ribose
-
?
poly(ADP-D-ribose)n + H2O binding structure of ADP-ribose to wild-type and mutant enzymes, overview Mus musculus poly(ADP-D-ribose)n-1 + ADP-ribose
-
?

Synonyms

Synonyms Comment Organism
PARG
-
Mus musculus

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.00012
-
pH and temperature not specified in the publication Mus musculus adenosine 5'-diphosphate-(hydroxymethyl)-pyrrolidinediol

General Information

General Information Comment Organism
additional information E748 and E749 are the key catalytic residues in the signature loop, N733 directly recognizes the 3'-OH on the proximal ribose, catalytic domain structure in apo- and liganded-states, overview. The N-terminal flexible peptide preceding the enzyme's catalytic domain may regulate the enzymatic activity, catalytic and regulatory mechanisms, overview. A binding site outside of the catalytic cleft for iso-ADP-ribose, which is probably the smallest enzyme subtrate containing the alpha(1->2) ribose-ribose glycosidic bond, may explain the processivity of the enzyme activity Mus musculus
physiological function protein poly(ADP-ribosyl)ation regulates a number of important cellular processes. Poly(ADP-ribose) glycohydrolase is the primary enzyme responsible for hydrolyzing the poly(ADP-ribose) polymer in vivo Mus musculus