Application | Comment | Organism |
---|---|---|
drug development | the protozoan enzyme represents a good model for human PARG and is therefore likely to prove useful in guiding structure-based discovery of new classes of PARG inhibitors | Tetrahymena thermophila |
Cloned (Comment) | Organism |
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phylogenetic analysis, expression of wild-type and selenomethionin-labeled enzymes in Escherichia coli strain Rosetta (DE3) | Tetrahymena thermophila |
Crystallization (Comment) | Organism |
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purified recombinant His-tagged enzyme in complex with ADP-ribose or inhibitor RBPI-3, and as selenomethionine-labeled enzyme, sitting drop vapour diffusion method, 15 mg/ml protein is mixed with a 1:1 molar ratio with ADP-ribose, and with an equal volume of a solution containing 0.15 M potassium thiocyanate, 0.1 M Tris, pH 8.5, and 15% PEG 6000, or with 0.2 M potassium bromide, 0.1 M Tris, pH 7.5, and 15% PEG 4000, X-ray diffraction structure determination and analysis at 1.95 A resolution | Tetrahymena thermophila |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
RBPI-3 | a rhodanine-containing mammalian PARG inhibitor, enzyme-inhibitor structure analysis, overview. RBPI-3 binds predominantly via a pi-pi stacking interaction with Tyr296 and the conserved Phe398. To accommodate the binding of RBPI-3, Phe398 moves into the adenosine binding pocket. The RBPI-3 carboxyl moiety occupies a region corresponding to the ADP-ribose alpha-phosphate group and H-bonds to main chain atoms of Lys365 and Gln254. The RBPI-3 di-chlorobenzyl moiety extends into the solvent and is disordered | Tetrahymena thermophila |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
poly(ADP-D-ribose)n + H2O | Tetrahymena thermophila | the activity is dependent on the conserved glutamate residues | poly(ADP-D-ribose)n-1 + ADP-ribose | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Tetrahymena thermophila | I6L8L8 | - |
- |
Purification (Comment) | Organism |
---|---|
recombinant His-tagged wild-type and selenomethionine-labeled enzymes from Escherichia coli strain Rosetta (DE3) by nickel affinity chromatography and gel filtration | Tetrahymena thermophila |
Reaction | Comment | Organism | Reaction ID |
---|---|---|---|
(ADP-ribose)n + H2O = (ADP-ribose)n-1 + ADP-ribose | canonical enzyme catalytic mechanism, modelling, overview | Tetrahymena thermophila |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
poly(ADP-D-ribose)n + H2O | the activity is dependent on the conserved glutamate residues | Tetrahymena thermophila | poly(ADP-D-ribose)n-1 + ADP-ribose | - |
? |
Subunits | Comment | Organism |
---|---|---|
More | the enzyme structure consists of a macrodomain sandwiched between a large N-terminal accessory domain and a smaller carboxy-terminal extension, structure overview | Tetrahymena thermophila |
Synonyms | Comment | Organism |
---|---|---|
PAR glycohydrolase | - |
Tetrahymena thermophila |
PARG | - |
Tetrahymena thermophila |
General Information | Comment | Organism |
---|---|---|
evolution | canonical poly(ADP-ribose) glycohydrolase is a highly conserved protein found in organisms ranging from protozoa to humans, phylogenetic analysis. The full-length enzyme from Tetrahymena thermophila is highly similar to the minimal catalytic region of thhe human enzyme, but it lacks the obvious RS/MTS motif | Tetrahymena thermophila |
additional information | enzyme structure overview | Tetrahymena thermophila |
physiological function | the reversion of poly(ADP-ribosyl)ation is catalysed by poly(ADP-ribose) glycohydrolase, which specifically targets the unique PAR (1''-2') ribose-ribose bonds | Tetrahymena thermophila |