Application | Comment | Organism |
---|---|---|
drug development | the enzyme is a target for drug design | Homo sapiens |
Cloned (Comment) | Organism |
---|---|
expression of His-tagged wild-type and mutant enzymes and selenomethionine-labeled enzyme in Escherichia coli strain BL21 (DE3) GOLD | Homo sapiens |
Crystallization (Comment) | Organism |
---|---|
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 | Comment | Organism |
---|---|---|
E688A | site-directed mutagenesis, a surface entropy reduction mutation | Homo sapiens |
K616A | site-directed mutagenesis, a surface entropy reduction mutation | Homo sapiens |
K616A/Q617A/K618A/E688A/K689A/K690A | site-directed mutagenesis, six surface entropy reduction mutations | Homo sapiens |
K618A | site-directed mutagenesis, a surface entropy reduction mutation | Homo sapiens |
K689A | site-directed mutagenesis, a surface entropy reduction mutation | Homo sapiens |
K690A | site-directed mutagenesis, a surface entropy reduction mutation | Homo sapiens |
Q617A | site-directed mutagenesis, a surface entropy reduction mutation | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
8-n-octyl-amino-adenosine 5'-diphosphate (hydroxymethyl)pyrrolidinediol | binding structure with mutant enzyme K616A/Q617A/K618A/E688A/K689A/K690A | Homo sapiens | |
adenosine 5'-diphosphate (hydroxymethyl)pyrrolidinediol | ADP-HPD, binding structure with mutant enzyme K616A/Q617A/K618A/E688A/K689A/K690A | Homo sapiens | |
ADP-ribose | binding structure with mutant enzyme K616A/Q617A/K618A/E688A/K689A/K690A | Homo sapiens | |
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 | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
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 | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | Q86W56 | - |
- |
Purification (Comment) | Organism |
---|---|
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 | Comment | Organism | Reaction ID |
---|---|---|---|
(ADP-ribose)n + H2O = (ADP-ribose)n-1 + ADP-ribose | enzyme catalytic mechanism, overview | Homo sapiens |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
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 | Comment | Organism |
---|---|---|
PARG | - |
Homo sapiens |
poly (ADP-ribose) glycohydrolase | - |
Homo sapiens |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
25 | - |
assay at | Homo sapiens |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7 | - |
assay at | Homo sapiens |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.0011 | - |
with mutant enzyme K616A/Q617A/K618A/E688A/K689A/K690A, pH 7.0, 25°C | Homo sapiens | adenosine 5'-diphosphate (hydroxymethyl)pyrrolidinediol | |
0.0031 | - |
with wild-type enzyme, pH 7.0, 25°C | Homo sapiens | adenosine 5'-diphosphate (hydroxymethyl)pyrrolidinediol | |
0.0163 | - |
with wild-type enzyme, pH 7.0, 25°C | Homo sapiens | 8-n-octyl-amino-adenosine 5'-diphosphate (hydroxymethyl)pyrrolidinediol |
General Information | Comment | Organism |
---|---|---|
evolution | conservation of overall fold amongst mammalian enzyme glycohydrolase domains, additional flexible regions in the catalytic site, overview | Homo sapiens |
malfunction | enzyme deficiency leads to cell death whilst enzyme depletion causes sensitisation to certain DNA damaging agents | Homo sapiens |
additional information | structure-based mechanism for the reported endo- and exo-glycohydrolase activities in human enzyme, overview | Homo sapiens |