Cloned (Comment) | Organism |
---|---|
gene CGAS, recombinant expression of isolated His-tagged h-cGAS catalytic domain in Escherichia coli strain Rosetta 2(DE3) | Homo sapiens |
Crystallization (Comment) | Organism |
---|---|
purified recombinant h-cGASCD in apoform and complexed with inhibitors, by hanging drop vapor diffusion method, mixing of 0.0015 ml of 8-9 mg/ml protein in 20 mM HEPES, pH 7.5, 250 mM KCl, 1 mM TCEP, and 10% glycerine, with 0.0015 ml of reservoir solution containing 17.5-19% v/v PEG 3350 and 0.2 M ammonium citrate, pH 7.0-7.5, 4°C, soaking of crystals for the inhibitor PF-06928215-enzyme complex, X-ray diffraction structure determination and analysis at 1.8 A resolution, molecular replacement using structure PDB ID 4LEV as a search model | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
(1R,2S)-2-(7-oxo-5-phenyl-4,7-dihydropyrazolo[1,5-a]pyrimidine-3-carboxamido)cyclohexane-1-carboxylic acid | PF-06928215, a commercial inhibitor, enzyme binding structure analysis, the pyrazolopyrimidine of PF-06928215 is sandwiched between the guanidinium group of R376 and the aromatic ring of Y436, mimicking the nucleobase. The benzene is anchored in a hydrophobic subpocket lined by the side chains of F488 and L490, molecular dynamics simulations, overview | Homo sapiens | |
(3R)-1-(pyrrolo[1,2-a]quinoxalin-4-yl)piperidine-3-carboxylic acid | 16.8% inhibition at 0.1 mM | Homo sapiens | |
1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinoline-6,7-dicarboxylic acid | 39.9% inhibition at 0.1 mM | Homo sapiens | |
1-[9-(6-aminopyridin-3-yl)-6,7-dichloro-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl]-2-hydroxyethan-1-one | - |
Homo sapiens | |
3-[1-(6,7-dichloro-1H-benzimidazol-2-yl)-5-hydroxy-3-methyl-pyrazol-4-yl]-3H-isobenzofuran-1-one | RU-521 or RU.521 | Homo sapiens | |
3-[5-(carboxymethyl)-3-oxo-3,5-dihydro[1,2,4]triazino[2,3-a]benzimidazol-2-yl]propanoic acid | 29.9% inhibition at 0.1 mM | Homo sapiens | |
4-[2-(2-methyl[1,2,4]triazolo[1,5-c]quinazolin-5-yl)hydrazinyl]-4-oxobutanoic acid | 21.8% inhibition at 0.1 mM | Homo sapiens | |
7-methoxy-N9-methyl-N9-[3-[methyl(pyridin-4-yl)amino]propyl]acridine-3,9-diamine | - |
Homo sapiens | |
additional information | in silico screening-based discovery of inhibitors of human cyclic GMP-AMP synthase, cross-validation study of molecular docking and experimental testing, usage of catalytic domain of human cGAS (h-cGASCD) for virtual screening, overview | Homo sapiens | |
suramin | - |
Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + GTP | Homo sapiens | overall reaction | 2 diphosphate + cyclic Gp(2'-5')Ap(3'-5') | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | Q8N884 | - |
- |
Purification (Comment) | Organism |
---|---|
recombinant His-tagged catalytic domain of h-cGAS from Escherichia coli strain Rosetta 2(DE3) by nickel affinity chromatography, dialysis, heparin ion exchange chromatography, and gel filtration | Homo sapiens |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + GTP | overall reaction | Homo sapiens | 2 diphosphate + cyclic Gp(2'-5')Ap(3'-5') | - |
? | |
additional information | a diphosphatase-coupled cGAS activity assay is performed | Homo sapiens | ? | - |
- |
Synonyms | Comment | Organism |
---|---|---|
cGAS | - |
Homo sapiens |
h-cGAS | - |
Homo sapiens |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
22 | - |
assay at room temperature | Homo sapiens |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7.5 | - |
assay at | Homo sapiens |
General Information | Comment | Organism |
---|---|---|
additional information | molecular dynamics simulations and structure modeling, overview | Homo sapiens |