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Literature summary extracted from

  • Tucker, J.A.; Bennett, N.; Brassington, C.; Durant, S.T.; Hassall, G.; Holdgate, G.; McAlister, M.; Nissink, J.W.; Truman, C.; Watson, M.
    Structures of the human poly (ADP-ribose) glycohydrolase catalytic domain confirm catalytic mechanism and explain inhibition by ADP-HPD derivatives (2012), PLoS ONE, 7, e50889.
    View publication on PubMedView publication on EuropePMC

Application

EC Number Application Comment Organism
3.2.1.143 drug development the enzyme is a target for drug design Homo sapiens

Cloned(Commentary)

EC Number Cloned (Comment) Organism
3.2.1.143 expression of His-tagged wild-type and mutant enzymes and selenomethionine-labeled enzyme in Escherichia coli strain BL21 (DE3) GOLD Homo sapiens

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
3.2.1.143 purified recombinant mutant K616A/Q617A/K618A/E688A/K689A/K690A, also in selenomethionine-labeld form, in complex with inhibitors, sitting drop vapour diffusion, mixing protein in SEC buffer at 7.5 mg/mL with a precipitant consisting of 28% PEG 3350, 0.2 M magnesium chloride, 0.1 M PCTP (0.04 M sodium propionate, 0.02 M sodium cacodylate, 0.04 M Bis-Tris propane), pH 7.5, in a 1:1 ratio to give a 0.004 ml drop, 20°C, X-ray diffraction structure determination and analysis at 1.75-1.83 A resolution, molecular replacement Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
3.2.1.143 E688A site-directed mutagenesis, a surface entropy reduction mutation Homo sapiens
3.2.1.143 K616A site-directed mutagenesis, a surface entropy reduction mutation Homo sapiens
3.2.1.143 K616A/Q617A/K618A/E688A/K689A/K690A site-directed mutagenesis, six surface entropy reduction mutations Homo sapiens
3.2.1.143 K618A site-directed mutagenesis, a surface entropy reduction mutation Homo sapiens
3.2.1.143 K689A site-directed mutagenesis, a surface entropy reduction mutation Homo sapiens
3.2.1.143 K690A site-directed mutagenesis, a surface entropy reduction mutation Homo sapiens
3.2.1.143 Q617A site-directed mutagenesis, a surface entropy reduction mutation Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
3.2.1.143 8-n-octyl-amino-adenosine 5'-diphosphate (hydroxymethyl)pyrrolidinediol binding structure with mutant enzyme K616A/Q617A/K618A/E688A/K689A/K690A Homo sapiens
3.2.1.143 adenosine 5'-diphosphate (hydroxymethyl)pyrrolidinediol ADP-HPD, binding structure with mutant enzyme K616A/Q617A/K618A/E688A/K689A/K690A Homo sapiens
3.2.1.143 ADP-ribose binding structure with mutant enzyme K616A/Q617A/K618A/E688A/K689A/K690A Homo sapiens
3.2.1.143 additional information structure-activity relationship analysis of the enzyme inhibitors by isothermal titration calorimetry and surface plasmon resonance, molecular modelling, overview Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
3.2.1.143 additional information Homo sapiens poly(ADP-ribose) glycohydrolase is the only enzyme known to catalyse hydrolysis of the O-glycosidic linkages of ADP-ribose polymers ?
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
3.2.1.143 Homo sapiens Q86W56
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
3.2.1.143 recombinant N-terminally, TEV protease-cleavable His6-tagged wild-type and mutant enzymes, and selenomethionine-labeled enzyme from Escherichia coli strains BL21 (DE3) GOLD and B834 (DE3) by nickel affinity chromatography and gel filtration Homo sapiens

Reaction

EC Number Reaction Comment Organism Reaction ID
3.2.1.143 (ADP-ribose)n + H2O = (ADP-ribose)n-1 + ADP-ribose enzyme catalytic mechanism, overview Homo sapiens
a

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
3.2.1.143 additional information poly(ADP-ribose) glycohydrolase is the only enzyme known to catalyse hydrolysis of the O-glycosidic linkages of ADP-ribose polymers Homo sapiens ?
-
 ?

Synonyms

EC Number Synonyms Comment Organism
3.2.1.143 PARG
-
 Homo sapiens
3.2.1.143 poly (ADP-ribose) glycohydrolase
-
 Homo sapiens

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
3.2.1.143 25
-
 assay at Homo sapiens

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
3.2.1.143 7
-
 assay at Homo sapiens

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
3.2.1.143 0.0011
-
 with mutant enzyme K616A/Q617A/K618A/E688A/K689A/K690A, pH 7.0, 25°C Homo sapiens adenosine 5'-diphosphate (hydroxymethyl)pyrrolidinediol
3.2.1.143 0.0031
-
 with wild-type enzyme, pH 7.0, 25°C Homo sapiens adenosine 5'-diphosphate (hydroxymethyl)pyrrolidinediol
3.2.1.143 0.0163
-
 with wild-type enzyme, pH 7.0, 25°C Homo sapiens 8-n-octyl-amino-adenosine 5'-diphosphate (hydroxymethyl)pyrrolidinediol

General Information

EC Number General Information Comment Organism
3.2.1.143 evolution conservation of overall fold amongst mammalian enzyme glycohydrolase domains, additional flexible regions in the catalytic site, overview Homo sapiens
3.2.1.143 malfunction enzyme deficiency leads to cell death whilst enzyme depletion causes sensitisation to certain DNA damaging agents Homo sapiens
3.2.1.143 additional information structure-based mechanism for the reported endo- and exo-glycohydrolase activities in human enzyme, overview Homo sapiens