Application | Comment | Organism |
---|---|---|
drug development | the enzyme is a potential target for antineoplastic intervention, design of IMPCH inhibitors, overview | Gallus gallus |
Crystallization (Comment) | Organism |
---|---|
enzyme in complex with inhibitors, sitting drop vapor diffusion method, 22°C, 10 mg/ml protein, mixing of equal volumes of protein and reservoir solutions, the latter containing 20% w/v PEG 8000, 0.2 M imidazole, pH 7.2, 5 mM dithiothreitol, X-ray diffraction structure determination and analysis at 2.0-2.7 A resolution | Gallus gallus |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
2,2-dioxo-1,5-dihydroimidazo[4,5-c][1,2,6]thiadiazin-4(3H)-one | construction of 1,5-dihydroimidazo[4,5-c][1,2,6]thiadiazin-4(3H)-one 2,2-dioxide, the corresponding nucleoside, and the nucleoside monophosphate, as mimics of the tetrahedral intermediate in the cyclization reaction. All compounds are competitive inhibitors against IMPCH, but the simpler heterocycle has a completely different IMPCH binding mode, compared to the nucleosides, and is relocated to the phosphate binding pocket, the aromatic imidazole ring interacts with a helix dipole, inhibitor synthesis, binding structure, and mechanism of inhibition, overview | Gallus gallus | |
7-(3,4-dihydroxy-5-hydroxymethyltetrahydrofuran-2-yl)-2,2-dioxo-1,5-dihydroimidazo[4,5-c][1,2,6]thiadiazin-4(3H)-one | construction of 1,5-dihydroimidazo[4,5-c][1,2,6]thiadiazin-4(3H)-one 2,2-dioxide, the corresponding nucleoside, and the nucleoside monophosphate, as mimics of the tetrahedral intermediate in the cyclization reaction. All compounds are competitive inhibitors against IMPCH, but the simpler heterocycle has a completely different IMPCH binding mode, compared to the nucleosides, and is relocated to the phosphate binding pocket, the aromatic imidazole ring interacts with a helix dipole, inhibitor synthesis, binding structure, and mechanism of inhibition, overview | Gallus gallus | |
phosphoric acid mono-[3,4-dihydroxy-5-(2,2,4-trioxo-1,5-dihydroimidazo[4,5-c][1,2,6]thiadiazin-7-yl)tetrahydrofuran-2-yl]methyl ester | construction of 1,5-dihydroimidazo[4,5-c][1,2,6]thiadiazin-4(3H)-one 2,2-dioxide, the corresponding nucleoside, and the nucleoside monophosphate, as mimics of the tetrahedral intermediate in the cyclization reaction. All compounds are competitive inhibitors against IMPCH, but the simpler heterocycle has a completely different IMPCH binding mode, compared to the nucleosides, and is relocated to the phosphate binding pocket, the aromatic imidazole ring interacts with a helix dipole, inhibitor synthesis, binding structure, and mechanism of inhibition, overview | Gallus gallus |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
additional information | Gallus gallus | bifunctional enzyme aminoimidazole-comprising the 4-carboxamide ribonucleotide transformylase, AICAR or Tfase, residues 200-593 and the IMPCH, ATIC, activities and catalyzes the final step in the de novo purine biosynthesis pathway that produces IMP, overview | ? | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Gallus gallus | P31335 | bifunctional protein, including EC 3.5.4.10 and EC 2.1.2.3 | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
additional information | bifunctional enzyme aminoimidazole-comprising the 4-carboxamide ribonucleotide transformylase, AICAR or Tfase, residues 200-593 and the IMPCH, ATIC, activities and catalyzes the final step in the de novo purine biosynthesis pathway that produces IMP, overview | Gallus gallus | ? | - |
? |
Synonyms | Comment | Organism |
---|---|---|
IMPCH | - |
Gallus gallus |
inosine monophosphate cyclohydrolase | - |
Gallus gallus |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7.4 | - |
assay at | Gallus gallus |
Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
---|---|---|---|---|---|
0.13 | - |
1,5-dihydroimidazo[4,5-c][1,2,6]thiadiazin-4(3H)-one 2,2-dioxide | pH 7.4 | Gallus gallus | |
0.15 | - |
phosphoric acid mono-[3,4-dihydroxy-5-(2,2,4-trioxo-1,5-dihydroimidazo[4,5-c][1,2,6]thiadiazin-7-yl)tetrahydrofuran-2-yl]methyl ester | about, pH 7.4 | Gallus gallus | |
0.23 | - |
7-(3,4-dihydroxy-5-hydroxymethyltetrahydrofuran-2-yl)-2,2-dioxo-1,5-dihydroimidazo[4,5-c][1,2,6]thiadiazin-4(3H)-one | about, pH 7.4 | Gallus gallus |