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Literature summary for 3.5.4.10 extracted from

  • Xu, L.; Chong, Y.; Hwang, I.; DOnofrio, A.; Amore, K.; Beardsley, G.P.; Li, C.; Olson, A.J.; Boger, D.L.; Wilson, I.A.
    Structure-based design, synthesis, evaluation, and crystal structures of transition state analogue inhibitors of inosine monophosphate cyclohydrolase (2007), J. Biol. Chem., 282, 13033-13046.
    View publication on PubMed

Application

Application Comment Organism
drug development the enzyme is a potential target for antineoplastic intervention, design of IMPCH inhibitors, overview Gallus gallus

Crystallization (Commentary)

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

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/ Products (Substrates)

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 ?
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?

Organism

Organism UniProt Comment Textmining
Gallus gallus P31335 bifunctional protein, including EC 3.5.4.10 and EC 2.1.2.3
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Substrates and Products (Substrate)

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 ?
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?

Synonyms

Synonyms Comment Organism
IMPCH
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Gallus gallus
inosine monophosphate cyclohydrolase
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Gallus gallus

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.4
-
assay at Gallus gallus

Ki Value [mM]

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