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Literature summary for 4.1.1.17 extracted from

  • Dufe, V.T.; Ingner, D.; Heby, O.; Khomutov, A.R.; Persson, L.; Al-Karadaghi, S.
    A structural insight into the inhibition of human and Leishmania donovani ornithine decarboxylases by 1-amino-oxy-3-aminopropane (2007), Biochem. J., 405, 261-268.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
expression in Escherichia coli strain BLR(DE3) Leishmania donovani
expression of His6-tagged enzyme in Escherichia coli strain BLR(DE3) Homo sapiens

Crystallization (Commentary)

Crystallization (Comment) Organism
purified recombinant His6-tagged enzyme in complex with inhibitor 1-amino-oxy-3-aminopropane or with both inhibitor and cofactor, sitting drop vapour diffusion method, 15C, 6 mg/ml protein in 25 mM HEPES, pH 7.2, 2 mM DTT, 0.5 mM EDTA, 0.02% Brij 35, 1 mM PMSF and 2 mM 1-amino-oxy-3-aminopropane, with or without 0.02 mM pyridoxal 5'-phosphate, mixed with well solution containing 25% v/v PEG 3350, 0.2 M ammonium acetate and 0.1 M Bis-Tris, pH 6.5, 2 days, needle-cluster crystals, single crystals are obtained by using a well solution containing 18% v/v PEG 3350, 0.2 M ammonium acetate, 0.1 M Bis-Tris, pH 6.5, and 3 mg/ml protein concentration, X-ray diffraction structure determination and analysis at 1.9-3.0 A resolution, molecular replacement Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
1-amino-oxy-3-aminopropane i.e. APA, analysis of the mode of the inhibitor binding to the enzyme, no oxime formation between APA and pyridoxal 5'-phosphate, homology modelling, overview Homo sapiens
1-amino-oxy-3-aminopropane i.e. APA, analysis of the mode of the inhibitor binding to the enzyme, no oxime formation between APA and pyridoxal 5'-phosphate, determined from the human enzyme-inhibitor cyrstal structure analysis and homology modelling, overview Leishmania donovani
alpha-difluoromethylornithine irreversible inhibitor, a curative agent of West African sleeping sickness Homo sapiens
alpha-difluoromethylornithine irreversible inhibitor Leishmania donovani

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
L-ornithine Leishmania donovani ODC is the first committed enzyme in the polyamine biosynthesis pathway putrescine + CO2
-
?
L-ornithine Homo sapiens ODC is the first committed enzyme in the polyamine biosynthesis pathway putrescine + CO2
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens P11926
-
-
Leishmania donovani
-
-
-

Purification (Commentary)

Purification (Comment) Organism
recombinant His6-tagged enzyme from Escherichia coli strain BLR(DE3) by nickel affinity chromatography Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
L-ornithine
-
Leishmania donovani putrescine + CO2
-
?
L-ornithine
-
Homo sapiens putrescine + CO2
-
?
L-ornithine ODC is the first committed enzyme in the polyamine biosynthesis pathway Leishmania donovani putrescine + CO2
-
?
L-ornithine ODC is the first committed enzyme in the polyamine biosynthesis pathway Homo sapiens putrescine + CO2
-
?

Synonyms

Synonyms Comment Organism
ODC
-
Leishmania donovani
ODC
-
Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
assay at Leishmania donovani
37
-
assay at Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.5
-
assay at Leishmania donovani
7.5
-
assay at Homo sapiens

Cofactor

Cofactor Comment Organism Structure
pyridoxal 5'-phosphate
-
Leishmania donovani
pyridoxal 5'-phosphate
-
Homo sapiens

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.000001
-
1-amino-oxy-3-aminopropane pH 7.5, 37°C, recombinant enzyme Leishmania donovani
0.000001
-
1-amino-oxy-3-aminopropane pH 7.5, 37°C, recombinant enzyme Homo sapiens