4.1.1.17: ornithine decarboxylase
This is an abbreviated version!
For detailed information about ornithine decarboxylase, go to the full flat file.
Word Map on EC 4.1.1.17
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4.1.1.17
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polyamine
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spermidine
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alpha-difluoromethylornithine
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carcinogenesis
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antizyme
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chemopreventive
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12-o-tetradecanoylphorbol-13-acetate
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phorbol
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mucosa
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difluoromethylornithine
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diamine
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decarboxylases
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n1-acetyltransferase
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hyperplasia
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arginase
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c-myc
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antiproliferative
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tpa-induced
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prostaglandin
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testosterone
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3hthymidine
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tumorigenesis
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mitogen
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cycloheximide
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c-fos
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methylglyoxal
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tpa-treated
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1,2-dimethylhydrazine
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isoproterenol
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hairless
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degrons
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12-o-tetradecanoyl
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hepatectomy
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cadaverine
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s-adenosyl-l-methionine
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drug development
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azoxymethane
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protooncogene
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papilloma
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7,12-dimethylbenzaanthracene
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agmatine
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phorbol-13-acetate
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medicine
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tumor-promoting
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food industry
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diagnostics
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nitrilotriacetate
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pharmacology
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prolactin
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crypt
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trypanothione
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12-o-tetradecanoylphorbol
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ester-induced
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actinomycin
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mezerein
- 4.1.1.17
- polyamine
- spermidine
- alpha-difluoromethylornithine
- carcinogenesis
- antizyme
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chemopreventive
- 12-o-tetradecanoylphorbol-13-acetate
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phorbol
- mucosa
- difluoromethylornithine
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diamine
- decarboxylases
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n1-acetyltransferase
- hyperplasia
- arginase
- c-myc
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antiproliferative
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tpa-induced
- prostaglandin
- testosterone
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3hthymidine
- tumorigenesis
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mitogen
- cycloheximide
- c-fos
- methylglyoxal
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tpa-treated
- 1,2-dimethylhydrazine
- isoproterenol
- hairless
- degrons
-
12-o-tetradecanoyl
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hepatectomy
- cadaverine
- s-adenosyl-l-methionine
- drug development
- azoxymethane
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protooncogene
- papilloma
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7,12-dimethylbenzaanthracene
- agmatine
- phorbol-13-acetate
- medicine
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tumor-promoting
- food industry
- diagnostics
- nitrilotriacetate
- pharmacology
- prolactin
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crypt
- trypanothione
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12-o-tetradecanoylphorbol
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ester-induced
- actinomycin
- mezerein
Reaction
Synonyms
AdoMetDC/ODC, BN36_1212510, bODC, DDB_G0281109, DdODC, Decarboxylase, ornithine, dODC, LDC/ODC, LdODC, lysine/ornithine decarboxylase, ODC, ODC-paralogue, ODC1, ornithine decarboxylase, PfAdoMetDC-ODC, PfODC/AdoMetDC, S-adenosylmethionine decarboxylase/ornithine decarboxylase, SpeC, XODC1, XODC2, YODC
ECTree
4.1.1.17 ornithine decarboxylaseAdvanced search results
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results (Inhibitors
Inhibitors on EC 4.1.1.17 - ornithine decarboxylase
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INHIBITOR 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
IMAGE
(-)-epigallocatechin-3-gallate
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polyphenolic compound of green tea with putative anti-cancer activity
(DL)-difluoromethylornithine
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irreversible inactivation, 50% inhibition at 0.0075 mM D-difluoromethylornithine
1,4-Dimethylputrescine
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none of the three isomers, meso, +, and - inhibits in vitro, but strongly inhibits in vivo in rats or in H-35 hepatoma cells
1-diethyl-2-hydroxy-2-nitroso-hydrazine
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nitric oxide donor, inhibition via S-nitrosylation of Cys360 in the active site of ODC
2-(difluoromethyl)-L-ornithine
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ODC suicide inhibitor, 5 mM alpha-difluromethylornithine reduces ODC activity by 45fold
2-difluoromethylornithine
DFMO, is used in therapy combined with MQT 1426, a polyamine transport inhibitor, for treatment of squamous cell carcinoma in a mouse model, K6/ODC
antizyme 1
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ODC is regulated by specific inhibitors, antizymes which in turn are inhibited by antizyme inhibitors. ODC alone is not degraded in reticulocyte lysate, whereas in the presence of antizyme 1, the degradation occurs rapidly. When antizyme inhibitor or ODC paralogue is added to the mixture, the antizyme 1-induced degradation of ODC is prevented.
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Antizyme1
AZ1, molecular basis for the inactivation of ODC by AZ1, analysis of the interactions between ODC and AZ1, overview. The ODC-cAZ1 complex forms a heterodimer, which consists of one ODC monomer and one AZ1 molecule, AZ1 is embedded into a concave surface formed between the N- and C-domains of ODC. Binding of the truncated cAZ1 to ODC occludes the binding of a second molecule of ODC to form the active homodimer, thus the substrate binding site is disrupted and ODC is inactivated. The binding of cAZ1 to ODC causes a global conformational change of ODC and renders its C-terminal region flexible, therefore exposing this region for degradation by the 26S proteasome. AZ1 inhibits ODC activity, exhibits anti-tumor activities, and may be considered a tumor suppressor
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CGP54619A
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3-amino-oxy-1-propanamine analog, 0.000025 mM, 50% inhibition of recombinant Pf-Hinge-ODC
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methyl N-[[3-hydroxy-5-(hydroxymethyl)-2-methylpyridin-4-yl]methyl]-1-methylhistidinate
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methyl N-[[3-hydroxy-5-(hydroxymethyl)-2-methylpyridin-4-yl]methyl]histidinate
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methyl N5-(tert-butoxycarbonyl)-N2-{[3-hydroxy-5-(hydroxymethyl)-2-methylpyridin-4-yl]methyl}-L-ornithinate
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N-acetylcysteine
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decreases enzyme activity in lung carcinoma NCI-H82 cells and reduces the cell viability, overview
peroxynitrite
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0.1 mM, 50% inhibition, almost complete inhibition above 1 mM, nitration of tyrosine residues
testosterone
29% decrease in activity in female mice, more important chnage in female compared to male mice, overview
testosterone propionate
decreases ODC activity by 56% in adrenal gland of castrated male mice, not in female mice
vitamin C
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decreases enzyme activity in lung carcinoma NCI-H82 cells and reduces the cell viability, overview
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
1-amino-oxy-3-aminopropane
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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
5,5'-dithiobis(2-nitrobenzoic acid)
0.001 mM, approx. 80% inhibition of ODC activity after 8 min
alpha-difluoromethylornithine
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5-10 mM, 25% inhibition in pellet, approx. 15% inhibition in supernatant, 20 mM, 40% inhibition in both pellet ans supernatant
alpha-difluoromethylornithine
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2 mM, 98% inhibition of ODC activity
alpha-difluoromethylornithine
DFMO, a suicide inhibitor, at 5 mM for 72 h, it inhibits membrane-associated ODC activity. Following exposure to alpha-DFMO, the putrescine content in the cells declineds, while the norspermidine content increases over 2fold. Partial inhibition of putrescine synthesis by alpha-DFMO results in increased norspermidine production in the cells suggesting that the suicide inhibitor may also act as an abiotic stress agent
alpha-difluoromethylornithine
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i.e. DFMO, irreversible inactivator, physiologic effects, e.g. causes arrest in G1 phase in neuroblastoma cells, the cytostatic effect is reversible by putrescine, overview, acts synergistically with SAM486A, MDL-73811, cisplatin, and 5-fluorouracil
alpha-difluoromethylornithine
irreversible inhibitor, a curative agent of West African sleeping sickness
alpha-difluoromethylornithine
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inhibition of ODC by alpha-difluoromethylornithine increases resistance to trichostatin A-induced cell death in HCT116 cells
alpha-difluoromethylornithine
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i.e. DFMO, ODC inhibition by alpha-difluoromethylornithine activates opposing signaling pathways via phosphorylation of both Akt/protein kinase B and p27Kip1 in neuroblastoma, inhibition of ODC by DFMO promotes cell survival by inducing the phosphorylation of Akt/PKB at residue Ser473 and glycogen synthase kinase-3B at Ser9, DFMO also induces the phosphorylation of p27Kip1 at residues Ser10, involved in nuclear export, and Thr198, involved in protein stabilization, but not Thr187, involved in proteasomal degradation,inhibition mechanism, overview
alpha-difluoromethylornithine
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DFMO, a Odc suicide inhibitor, selective anticancer effects of DFMO on mouse and human MYCN-amplified neuroblastoma, overview
alpha-difluoromethylornithine
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an irreversible inhibitor of ODC, cannot recover MMP-9 activation following NF-kappaB inhibitor treatment in parental cells
alpha-difluoromethylornithine
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an enzyme-activated irreversible inhibitor, effective sue to the slow turnover of the trypanosomatid enzyme
alpha-difluoromethylornithine
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a suicide inhibitor of ODC, inhibits growth of wild-type Leishmania donovani amastigotes and effectively cures macrophages of parasites, thereby preventing host cell destruction
alpha-difluoromethylornithine
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an enzyme-activated irreversible inhibitor, effective sue to the slow turnover of the trypanosomatid enzyme
alpha-difluoromethylornithine
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i.e. DFMO, irreversible inactivator, antitumor action of ODC inhibition using DFMO, chemopreventive effects, DFMO provides significant protection against N-butyl-N(4-hydroxybutyl)-nitrosamine-induced bladder cancer, overview
alpha-difluoromethylornithine
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the enzyme is inhibited in the combination therapy with 2-difluoromethylornithine and a polyamine transport inhibitor MQT 1426, i.e. D-Lys-spermine, against squamous cell carcinoma, the apoptotic index of the cells is transiently increased by combination therapy but not by DFMO alone, a K6/ODC mouse model, overview
alpha-difluoromethylornithine
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i.e. DFMO, irreversible inactivator, antitumor action of ODC inhibition using DFMO, chemopreventive effects, DFMO provides significant protection against 7,12-dimethylbenz[a]-anthracene-induced mammary carcinogenesis, overview
alpha-difluoromethylornithine
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specific and irreversible ODC inhibitor, complete inhibition at 0.1 mM
alpha-difluoromethylornithine
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an enzyme-activated irreversible inhibitor, effective sue to the slow turnover of the trypanosomatid enzyme
alpha-difluoromethylornithine
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an enzyme-activated irreversible inhibitor, effective sue to the slow turnover of the trypanosomatid enzyme
alpha-difluoromethylornithine
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a highly specific suicide inhibitor of ODC causing complete, irreversible inhibition
alpha-DL-difluoromethylornithine
a medically used, irreversible inhibitor of ODC
alpha-DL-difluoromethylornithine
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irreversibel; mechanism of irreversible inactivation
alpha-DL-difluoromethylornithine
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experimental interruption of pregnancy in the mouse
alpha-DL-difluoromethylornithine
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the nuclear enzyme is slightly more sensitive than the cytosolic
antizyme
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non-competitive protein inhibitor of ODC. Binding of antizyme to an ODC monomer subunit results in enzymatic inhibition, rapid ubiquitin-independent degradation of ODC by the 26S proteasome and recycling of antizyme
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antizyme
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non-competitive inhibitor protein isolated from Thermus thermophilus or Escherichia coli, almost complete inhibition at higer concentrations
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antizyme
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an important endogenous regulator of ODC and polyamine homeostasis, overview, the wild type form of ODC has an extremely short half life of 20-30 min, and its degradation is mediated by antizyme, which binds to the monomeric form of ODC, preventing formation of the enzymatically active homodimer, and then targets ODC for degradation
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antizyme
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the ornithine decarboxylase paralogue antizyme inhibitor ODCp acts as a regulator of ODC activity and inhibits its proteasomal degradation. ODCp binds antizymes, AZs, with higher affinity than does ODC and releases active ODC from catalytically inactive ODC-AZ complexes, overview
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antizyme
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antizymes are small polyamine-induced proteins that function as feedback regulators of cellular polyamine homeostasis. They bind to transient ODC monomeric subunits, resulting in inhibition of ODC activity and targeting ODC to ubiquitin-independent proteasomal degradation, unlike antizyme 1 and antizyme 2, which efficiently inhibit ODC activity and stimulate its proteasomal degradation, antizyme 3 poorly inhibits ODC activity and fails to promote ODC degradation. Furthermore, Az3 actually stabilizes ODC, probably by protecting it from the effect of Az1, overview. Interaction with antizyme stimulates ODC degradation due to a conformational change resulting in the exposure of it C-terminal proteasome recognition signal, overview. Az2 and Az3 are cloned by RT-PCR using RNA isolated from mouse liver and testis respectively, and expressed in HEK-293 cells
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antizyme
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an important endogenous regulator of ODC and polyamine homeostasis, overview, the wild type form of ODC has an extremely short half life of 20-30 min, and its degradation is mediated by antizyme, which binds to the monomeric form of ODC, preventing formation of the enzymatically active homodimer, and then targets ODC for degradation
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antizyme
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there are multiple antizyme genes with at least four members, all members, which are localized in different compartments or tissue, inhibit ODC activity, overview, the antizyme inhibitor blocks the effects of antizyme on the enzyme, overview
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antizyme
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role of ornithine decarboxylase antizyme inhibitor in vivo, ODC antizyme inhibitor, AZI, regulates ODC activity in cell cultures
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antizyme
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an important endogenous regulator of ODC and polyamine homeostasis, overview, the wild type form of ODC has an extremely short half life of 20-30 min, and its degradation is mediated by antizyme, which binds to the monomeric form of ODC, preventing formation of the enzymatically active homodimer, and then targets ODC for degradation
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antizyme
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yeast, determination of sequences that are important for inhibiting ODC activity and promoting ODC degradation, the yeast ODC is not affected by mammalian antizyme
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antizyme
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non-competitive inhibitor protein isolated from Thermus thermophilus
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antizyme
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ODC antizyme, a polyamine-induced protein, binds ODC, serving to inhibit ODC activity and to promote proteasome-mediated ODC degradation
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CGP52622A
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3-amino-oxy-1-propanamine analog, 0.00006 mM, 50% inhibition of recombinant Pf-Hinge-ODC
DL-alpha-difluoromethylornithine
DFMO, an irreversible suicide inhibitor. DFMO inhibits growth of endometrial cancer cells in vitro and DFMO treatment significantly reduces endometrial tumor growth in vivo
DL-alpha-difluoromethylornithine
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1.5 mM DL-alpha-difluoromethylornithine is an effective inhibitor of ODC. In the absence of phenanthrene, treatment reduces ODC activity by 52%.
L-arginine
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L-arginine reduces cell proliferation and ornithine decarboxylase activity in patients with colorectal adenoma and adenocarcinoma, overview
Ornithine decarboxylase antizyme
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ornithine decarboxylase antizymes are proteins which negatively regulate cellular polyamine levels via their affects on polyamine synthesis and cellular uptake, development of a computer tool, OAF or ODC antizyme finder, for identifying antizyme encoding sequences in spliced or intronless nucleic acid sequenes, overview
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Ornithine decarboxylase antizyme
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noncompetitive with respect to Orn, plays a role in the regulation of ornithine decarboxylase in mammary gland under physiological conditions
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spermidine
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1 mM, 61% inhibition of recombinant-Hinge-ODC and 63% inhibition of recombinant PfODC
additional information
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Arabidopsis S15 ribosomal protein does not inhibit the enzymatic activity of the plant ODC
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additional information
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ODC activity decreases by 30-50% after incubation of cells with 1 mM putrescine, 0.1 mM spermidine or 0.1 mM spermine
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additional information
alpha-difluoromethylarginine, DFMA, a suicide inhibitor, does not inhibit the enzyme
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additional information
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alpha-difluoromethylarginine, DFMA, a suicide inhibitor, does not inhibit the enzyme
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additional information
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treatment of protozoan diseases by inhibitors of ornithine decarboxylase
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additional information
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not inhibited by alpha-difluoromethylornithine
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additional information
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12-15% inhibition at 4-8 mg/ml by an ethanolic extract from the stem bark of Bursera fagaroides, collected during January 2004 in the region of Capula, Michoacan, Mexico, on ODC activity in vitro and on the growth of Entamoeba histolytica, overview
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additional information
no inhibition of the Entamoeba histolytica enzyme by specific irreversible ODC inhibitor alpha-difluoromethylornithine, DFMO, the recombinant enzyme shows altered amino acid sequence and three-dimensional structure, Entamoeba histolytica putative ODC has a putative binding site for DFMO with substituted disrupted amino acids D332, D361, and Y323 by H296, F305, and N334, through which this inhibitor interacts with the protein
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additional information
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no inhibition of the Entamoeba histolytica enzyme by specific irreversible ODC inhibitor alpha-difluoromethylornithine, DFMO, the recombinant enzyme shows altered amino acid sequence and three-dimensional structure, Entamoeba histolytica putative ODC has a putative binding site for DFMO with substituted disrupted amino acids D332, D361, and Y323 by H296, F305, and N334, through which this inhibitor interacts with the protein
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additional information
enzyme from Entamoeba histolytica is resistant to the irreversible inhibitor of ornithine decarboxylases, a-difluoromethylornithine. crystallographic data
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additional information
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enzyme from Entamoeba histolytica is resistant to the irreversible inhibitor of ornithine decarboxylases, a-difluoromethylornithine. crystallographic data
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additional information
stilbamine isethionate, up to 0.1 mM, shows no inhibition
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additional information
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stilbamine isethionate, up to 0.1 mM, shows no inhibition
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additional information
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enzyme activity decreases upon addition of L-arginine or L-methionine to growth medium, but L-arginine or L-methionine are not inhibitory to enzyme
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additional information
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some chemotherapeutic agents aim at reducing ODC expression and show inhibitory effects on cancer cell growth, overview
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additional information
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the enzyme is induced by phorbol esters, rapamycin, which blocks phosphorylation of 4E-BP1, inhibits the induction of ODC in response to serum
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additional information
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Bcl-2 has no effect on the activity and expression of ODC
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additional information
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serum deprivation reduces enzyme activity by 87.6% in SH-SY5Y cells, overview, enzyme activity is not affected in secondary cell lines exposed to 872 MHz RF radiation, overview
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additional information
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ODC is degraded in an ubiquitin-independent manner mediated by antizyme 1
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additional information
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enzyme degradation is enhanced by antizyme, a polyamine-induced protein, this is prevented by ODCp, a brain- and testis-specific ornithine decarboxylase paralogue, overview
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additional information
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hypoxia deminishes ODC expression, ODC inhibition enhances the anti-tumor effect of antiangiogenesis therapy
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additional information
no inhibition by phosphopyridoxyl-pyridine-D-Ala and BOC-protected phosphopyridoxyl-alpha,gamma-diaminobutyric acid, coenzyme derivative inhibitor development, molecular modeling and inhibition mechanism, binding model of the phosphopyridoxyl conjugates in the active site of hODC, overview
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additional information
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no inhibition by phosphopyridoxyl-pyridine-D-Ala and BOC-protected phosphopyridoxyl-alpha,gamma-diaminobutyric acid, coenzyme derivative inhibitor development, molecular modeling and inhibition mechanism, binding model of the phosphopyridoxyl conjugates in the active site of hODC, overview
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additional information
not inhibitory: alpha-difluoromethylornithine
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additional information
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inhibition of ODC activity reverts the transformation of cells in vitro and reduces tumor growth
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additional information
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enzyme activity is not affected in secondary cell lines exposed to 872 MHz RF radiation, overview
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additional information
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enzyme degradation is enhanced by antizyme, a polyamine-induced protein, this is prevented by ODCp, a brain- and testis-specific ornithine decarboxylase paralogue, overview
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additional information
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radiation at 5 W/kg does not affect the enzyme activity or cell proliferation and caspase-3 activity in L-929 cells
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additional information
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hemin reduces the 12-O-tetradecanoylphorobl-13-acetate-induced expression of ODC, and hemin suppresses the 12-O-tetradecanoylphorobl-13-acetate-induced activation of extracellular signal-regulated protein kinase and p38 MAPK
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additional information
MQT 1426 has no inhibitory effect on squamous cell carcinoma ODC activity nor does it enhance the inhibition by 2-difluoromethylornithine, but it reduces the polyamine levels in squamous cell carcinoma cells
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additional information
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protein kinase phosphorylates ornithine decarboxylase, the reaction is dependent on spermine and spermidine, phosphorylation of ornithine decarboxylase inhibits its capacity to catalyze decarboxylation of L-Orn
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additional information
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ODC inhibition decreases putrescine levels, AdoMetDC inhibition decreases the levels of both spermidine and spermine
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additional information
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RR-methyl acetylenic putrescine has no significant effect
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additional information
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RR-methyl acetylenic putrescine has no significant effect
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additional information
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subcutaneous injection of 10 mg of dexamethasone/kg body weight decreases significantly the basal levels of lung ODC activity
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additional information
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inhibition of ODC activity reverts the transformation of cells in vitro and reduces tumor growth
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additional information
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serum deprivation reduces enzyme activity by 97.2% and by 87.0% in C6 cells, overview, enzyme activity is affected in primary astrocytes but not in secondary cell lines exposed to 872 MHz RF radiation, overview
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additional information
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ODC is inhibited by MAPK kinase, PKA, and PI3K inhibitors
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additional information
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treatment of plants exposed to phenanthrene with DL-alpha-difluoromethylarginine does not result in any major changes to the trends in ODC activity observed in plants exposed to phenanthrene; treatment with methylglyoxal-bis(guanylhydrazone) does not significantly influence ODC activity
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additional information
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ornithine decarboxylase and antizyme protein form a complex with 1:1 stoichiometry. Antizyme inhibits ornithine decarboxylase and faclilitates its degradation. The association constant is 6000000 per M. Circular dichroism spectra show a change in the secondary structure of the proteins in the complex
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additional information
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the enzyme is an important target for antitrypanosomal chemotherapy
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additional information
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treatment of protozoan diseases by inhibitors of ornithine decarboxylase
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