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Information on EC 2.6.1.13 - ornithine aminotransferase and Organism(s) Homo sapiens and UniProt Accession P04181
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2.6.1.13 ornithine aminotransferaseIUBMB Comments
A pyridoxal-phosphate protein.
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Word Map
- 2.6.1.13
- atrophy
-
gyrate
- arginase
- retina
- choroid
- pyridoxal
- polyamines
-
chorioretinal
-
hyperornithinemia
- citrulline
- putrescine
-
transamination
- aminotransferases
- delta1-pyrroline-5-carboxylate
- 1-pyrroline-5-carboxylate
- argininosuccinate
- gabaculine
-
hyperammonemias
- carbamoylphosphate
- biotechnology
- medicine
-
plp-dependent
- analysis
- drug development
- diagnostics
- agriculture
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Reaction Schemes
Synonyms
ornithine aminotransferase, ornithine-delta-aminotransferase, ornithine transaminase, ornithine delta-aminotransferase, psoat, delta-oat, ornithine amino transferase, l-ornithine:2-oxoacid aminotransferase, taoat, ornithine delta-transaminase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
aminotransferase, ornithine-keto acid
-
-
-
-
L-ornithine 5-aminotransferase
-
-
-
-
L-ornithine aminotransferase
-
-
-
-
L-ornithine:alpha-ketoglutarate delta-aminotransferase
-
-
-
-
OAT
ornithine 5-aminotransferase
-
-
-
-
ornithine aminotransferase
ornithine delta-transaminase
-
-
-
-
ornithine transaminase
-
-
-
-
ornithine-2-oxoacid aminotransferase
-
-
-
-
ornithine-alpha-ketoglutarate aminotransferase
-
-
-
-
ornithine-keto acid aminotransferase
-
-
-
-
ornithine-keto acid transaminase
-
-
-
-
ornithine-ketoglutarate aminotransferase
-
-
-
-
ornithine-oxo acid aminotransferase
-
-
-
-
ornithine-oxo-acid transaminase
-
-
-
-
ornithine:alpha-oxoglutarate transaminase
-
-
-
-
OAT
-
-
-
-
ornithine aminotransferase
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
L-ornithine + a 2-oxo carboxylate = L-glutamate 5-semialdehyde + an L-amino acid
mechanism
-
L-ornithine + a 2-oxo carboxylate = L-glutamate 5-semialdehyde + an L-amino acid
mechanism of the L-ornithine transamination catalysed by ornithine aminotransferase (OAT) and reaction intermediate forms, detailed overview. Like every PLP-dependent transaminases, OAT operates via a ping-pong mechanism, in which two half-reactions complete a full transamination cycle. In the first half-transamination reaction, L-ornithine reacts with the PLP form of the enzyme (OAT-PLP) to yield L-glutamate 5-semialdehyde and the pyridoxamine 5'-phosphate form of the enzyme (OAT-PMP). In the second half transamination, 2-oxoglutarate reacts with OAT-PMP to reform OAT-PLP and L-glutamate
L-ornithine + a 2-oxo carboxylate = L-glutamate 5-semialdehyde + an L-amino acid
the enzyme performs a OAT-like PLP-dependent transaminase ping-pong mechanism, two half-reactions completing a full transamination cycle. Like other transaminases, ornithine delta-aminotransferase (OAT) in the absence of substrates forms an internal aldimine with the PLP cofactor covalently bound on a lysine residue through a Schiff base. In the first half-reaction, ornithine forms an external aldimine with PLP, no longer covalently bound to the enzyme, but retained in the active site through non-covalent interactions. Enzyme OAT thus acts as an omega-transaminase in the first half-reaction, and as an alpha-transaminase in the second half-reaction: although the alpha-amino group is more reactive then the distal one, in the first half-reaction OAT transaminates the distal OAT amino group
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
amino group transfer
amino group transfer
-
-
-
-
PATHWAY SOURCE
PATHWAYS
BRENDA
-
-, -, -, -, -, -, -
SYSTEMATIC NAME
IUBMB Comments
L-ornithine:2-oxo-acid aminotransferase
A pyridoxal-phosphate protein.
CAS REGISTRY NUMBER
COMMENTARY
9030-42-6
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
L-ornithine + 2-oxoglutarate
DELTA1-pyrroline-5-carboxylate + glutamate
-
-
-
?
L-ornithine + 2-oxoglutarate
DELTA1-pyrroline-5-carboxylate + L-glutamate
-
-
-
r
L-ornithine + 2-oxoglutarate
glutamate + DELTA1-pyrroline-5-carboxylate
-
-
-
-
?
L-ornithine + 2-oxoglutarate
L-glutamate 5-semialdehyde + L-glutamate
-
-
-
r
L-ornithine + 2-oxoglutarate
L-glutamate 5-semialdehyde + L-glutamate
-
-
-
r
L-ornithine + 2-oxoglutarate
L-glutamate 5-semialdehyde + L-glutamate
the forward reaction is favoured
-
-
r
L-ornithine + 2-oxoglutarate
DELTA1-pyrroline-5-carboxylate + L-glutamate
-
-
-
-
?
L-ornithine + 2-oxoglutarate
DELTA1-pyrroline-5-carboxylate + L-glutamate
-
-
glutamate-gamma semialdehyde spontaneously cyclizes to form DELTA1-pyrroline-5-carboxylate
?
L-ornithine + 2-oxoglutarate
DELTA1-pyrroline-5-carboxylate + L-glutamate
-
urea cycle
-
-
?
additional information
?
-
glutamic-gamma-semialdehyde (GSA) product of this reaction undergoes spontaneous cyclization forming DELTA1-pyrroline-5-carboxylate (P5C). NMR analysis of P5C and of 1-pyrroline-2-carboxylate (P2C), generated by alpha-transamination of L-ornithine. Substrate molecular docking study and interaction analysis, NMR analysis, overview
-
-
-
additional information
?
-
spontaneous cyclization of glutamate 5-semialdehyde (GSA) to form (S)-DELTA1-pyrroline-5-carboxylate (P5C), the aldehyde can spontaneously react to give a hydrated form of GSA, making the reaction almost irreversible in vitro
-
-
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
L-ornithine + 2-oxoglutarate
L-glutamate 5-semialdehyde + L-glutamate
-
-
-
r
L-ornithine + 2-oxoglutarate
L-glutamate 5-semialdehyde + L-glutamate
-
-
-
r
L-ornithine + 2-oxoglutarate
DELTA1-pyrroline-5-carboxylate + L-glutamate
-
-
-
-
?
L-ornithine + 2-oxoglutarate
DELTA1-pyrroline-5-carboxylate + L-glutamate
-
urea cycle
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
pyridoxal 5'-phosphate
PLP, dependent on, purified hOAT bind about 2 moles of PLP/mol of enzyme dimer
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(1R,3S,4S)-3-amino-4-fluorocyclopentane-1-carboxylic acid
a nonselective aminotransferase inactivator
(1S,3S)-3-amino-4-(1,1,1,3,3,3-hexafluoropropan-2-ylidene)cyclopentane-1-carboxylic acid
-
(2S,5S)-5-fluoromethylornithine
-
it blocks the enzyme by a suicide reaction (mechanism-based inhibition) leading to a covalent adduct with the cofactor
additional information
design, synthesis, and evaluation of a series of fluorine-substituted cyclohexene analogues, as selective hOAT inhibitors, overview. Molecular dynamics simulations and electrostatic potential charge calculations are conducted to elucidated the significant influence of the one-fluorine difference on the corresponding intermediates, leading to two totally different inactivation pathways. Binding analysis of inhibitors 8 and 9 using the structure of hOAT (PDB ID 1OAT)
-
additional information
-
design, synthesis, and evaluation of a series of fluorine-substituted cyclohexene analogues, as selective hOAT inhibitors, overview. Molecular dynamics simulations and electrostatic potential charge calculations are conducted to elucidated the significant influence of the one-fluorine difference on the corresponding intermediates, leading to two totally different inactivation pathways. Binding analysis of inhibitors 8 and 9 using the structure of hOAT (PDB ID 1OAT)
-
additional information
inactivation mechanism, detailed overview. The compound shows enhanced potency, along with excellent selectivity over other aminotransferases. Enzyme binding structure analysis
-
additional information
-
inactivation mechanism, detailed overview. The compound shows enhanced potency, along with excellent selectivity over other aminotransferases. Enzyme binding structure analysis
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
retinoic acid
-
treatment of cells induces increase in ornithine aminotransferase expression and activity which results in decreased intracellular concentrations of ornithine and polyamines putrescine, spermidine and spermine. Changes occur concomitantly with a decrease in the total number of cells, and the increase in ornithine aminotransferase activity is due to increased mRNA expression. In cells treated with 1 microM retinoic acid, addition of 10 microM putrescine to culture medium restores both cellular levels of polyamines and cell numbers to the values for the control group
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2.75
2-oxoglutarate
pH and temperature not specified in the publication, eye iris enzyme
3.9
2-oxoglutarate
pH 8.0, 25°C, recombinant wild-type enzyme, 60 nM enzyme
4
2-oxoglutarate
pH 8.0, 15°C, recombinant wild-ype enzyme, 0.001 mM enzyme
4.4
2-oxoglutarate
pH 8.0, 15°C, recombinant mutant R217A, 0.001 mM enzyme
3.7
L-ornithine
pH and temperature not specified in the publication, eye retina enzyme
7
L-ornithine
pH 8.0, 15°C, recombinant wild-type enzyme, 0.001 mM enzyme
10.5
L-ornithine
assay based on reduction of DELTA1-pyrroline-5-carboxylate, pH 8.0, 37°C
additional information
additional information
Michaelis-Menten steady-state kinetics
-
additional information
additional information
-
Michaelis-Menten steady-state kinetics
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
20
2-oxoglutarate
pH 8.0, 15°C, recombinant wild-ype enzyme, 0.001 mM enzyme
20.7
2-oxoglutarate
pH 8.0, 15°C, recombinant mutant R217A, 0.001 mM enzyme
35.7
2-oxoglutarate
pH 8.0, 25°C, recombinant wild-ype enzyme, 60 nM enzyme
22.6
L-ornithine
pH 8.0, 15°C, recombinant wild-type enzyme, 0.001 mM enzyme
34.9
L-ornithine
pH 8.0, 25°C, recombinant wild-type enzyme, 60 nM enzyme
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
4.7
2-oxoglutarate
pH 8.0, 15°C, recombinant mutant R217A, 0.001 mM enzyme
5
2-oxoglutarate
pH 8.0, 15°C, recombinant wild-ype enzyme, 0.001 mM enzyme
3.2
L-ornithine
pH 8.0, 15°C, recombinant wild-type enzyme, 0.001 mM enzyme
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1.4
(1R,3S,4S)-3-amino-4-fluorocyclopentane-1-carboxylic acid
Homo sapiens
pH 8.0, temperature not specified in the publication
0.065
(1S,3S)-3-amino-4-(1,1,1,3,3,3-hexafluoropropan-2-ylidene)cyclopentane-1-carboxylic acid
Homo sapiens
pH 8.0, temperature not specified in the publication
0.0023
(3S)-3-amino-4,4-difluorocyclohex-1-ene-1-carboxylic acid
Homo sapiens
pH 8.0, temperature not specified in the publication
0.031
(3S,4S)-3-amino-4-fluorocyclohex-1-ene-1-carboxylic acid
Homo sapiens
pH 8.0, temperature not specified in the publication
4.38
(4S,5S)-5-amino-4-fluorocyclohex-1-ene-1-carboxylic acid
Homo sapiens
pH 8.0, temperature not specified in the publication
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.00275
pH and temperature not specified in the publication, eye iris enzyme
5.22
assay based on reduction of DELTA1-pyrroline-5-carboxylate, pH 8.0, 37°C
0.00024
0.00133
-
DELTA1-pyrroline-5-carboxylate is formed per mg enzyme per minute in lysates from white blood cells, with 0.05 mM pyridoxal 5'-phosphate, in 50 mM Tris-HCl, pH 8.0
0.00228
-
DELTA1-pyrroline-5-carboxylate is formed per mg enzyme per minute in lysates from platelets, with 0.05 mM pyridoxal 5'-phosphate, in 50 mM Tris-HCl, pH 8.0
0.00024
-
DELTA1-pyrroline-5-carboxylate is formed per mg enzyme per minute in lysates from platelets, without cofactor pyridoxal 5'-phosphate, in 50 mM Tris-HCl, pH 8.0
0.00024
-
DELTA1-pyrroline-5-carboxylate is formed per mg enzyme per minute in lysates from white blood cells, without cofactor pyridoxal 5'-phosphate, in 50 mM Tris-HCl, pH 8.0
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7 - 9
-
pH 7.0: about 50% of activity maximum, pH 9.0: about 60% of activity maximum
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
NSCLC cell. Upregulation of OAT in NSCLC tissues
additional information
tissue expression profile, overview. OAT can be found in almost all tissues, but its activity predominates in the liver, kidney, intestine, and retina
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
the mitochondrial localization may control the reaction kinetics, OAT activity being apparently limited by the rate of ornithine entry into the mitochondrion
additional information
OAT is synthesized as a 49 kDa precursor in the cytosol and it is then imported into mitochondria where it reaches the functional conformation upon removal of an N-terminal mitochondrial targeting sequence (residues 1-25) producing a about 45 kDa mature protein
-
additional information
-
OAT is synthesized as a 49 kDa precursor in the cytosol and it is then imported into mitochondria where it reaches the functional conformation upon removal of an N-terminal mitochondrial targeting sequence (residues 1-25) producing a about 45 kDa mature protein
-
additional information
the human enzyme is synthesized on cytoplasmic free ribosomes as a 45 kDa precursor and is processed into a mature protein after mitochondrial entry
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
the ornithine delta-transaminase, OAT, stands at the crossroads of several metabolic pathways. The role of enzyme OAT in ornithine fluxes, overview
physiological function
malfunction
-
the influence of OAT activity in a model of septic shock induced by intraperitoneal injection of lipopolysaccharide in wild-type and transgenic mice overexpressing OAT in the liver, kidney and intestine is analysed. OAT overexpression has only limited metabolic consequences, most probably because of compensatory mechanisms ensuring amino acid homeostasis. OAT overexpression brings a metabolic advantage in the response to stress. Results show an inhibition of OAT activity and expression in the liver following LPS treatment
malfunction
a deficit in ornithine aminotransferase (OAT) is associated with gyrate atrophy, a rare autosomal recessive disorder causing progressive blindness and chorioretinal degeneration
malfunction
overexpression of OAT promotes the growth and metastasis of A-549 lung cancer cells, and overexpression of OAT also promotes the epithelial-mesenchymal transition (EMT) of OAT-overexpressing A549 cells. Knockdown of OAT inhibits the proliferation and metastasis of H-1299 cells
malfunction
selective inhibition of hOAT has been shown to effectively suppress hepatocellular carcinoma (HCC) tumor growth in vivo
malfunction
the R180T variant of delta-ornithine aminotransferase is associated with gyrate atrophy. Ornithine delta-aminotransferase deficiency is responsible for gyrate atrophy (GA), an autosomal recessive disorder causing a progressive degeneration of the choroid and retina epithelium leading to blindness in young adults
malfunction
toxic effect of elevated intraocular concentrations of ornithine and its metabolites in excess, such as spermine, on the retinal pigment epithelial cells, together with Pro deficiency in the choroid and retina
physiological function
human ornithine aminotransferase (hOAT), a pyridoxal 5'-phosphate-dependent enzyme, plays a critical role in the progression of hepatocellular carcinoma (HCC) and in the metabolic reprograming of HCC via proline and glutamine metabolic pathways
physiological function
ornithine aminotransferase (OAT) promotes the proliferation, invasion, and migration, inhibits the apoptosis, and alters cell cycle of non-small cell lung cancer cells (NSCLC cells). Also the involvement of OAT-miR-21-glycogen synthase kinase-3beta signaling in the functional role of OAT in NSCLC is revealed. Glycogen synthase kinase-3beta (GSK-3beta) is a direct target of miR-21 in NSCLC
physiological function
ornithine delta-aminotransferase (OAT) is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that catalyzes the delta-transamination of L-ornithine and 2-oxoglutarate to glutamic-gamma-semialdehyde (GSA) and L-glutamate in the mitochondrial matrix. GSA then spontaneously cyclizes forming pirroline-5-carboxylate (P5C), a proline precursor
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). OAT_HUMAN
439
0
48535
Swiss-Prot
Mitochondrion (Reliability: 1)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
182000 - 183000
recombinant tetrameric wild-type enzyme, gel filtration and analytical ultracentrifugation sedimentation analysis
88000
recombinant dimeric mutant R217A, gel filtration and analytical ultracentrifugation sedimentation analysis
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
tetramer
4 * 45000, mature enzyme, SDS-PAGE, 4 * 49000, pro-enzyme, SDS-PAGE, dimer of dimers
homodimer
-
the crystal structure of the human enzyme is determined, the functional unit of the protein consists of a dimer built from 2 identical subunits, each monomer contains 12 alpha-helices and 14 beta-strands and can be structurally divided into 3 domains: a large 249 residue domain (PLP-binding domain), a small C-terminal domain of 95 residues and an N-terminal segment of 42 residues
additional information
additional information
apo and holo-hOAT enzymes (a) show a similar tertiary structure, even if apo displays a more pronounced exposure of hydrophobic patches, and (b) exhibit a tetrameric structure with a tetramer-dimer equilibrium dissociation constant about fivefold higher for the apoform with respect to the holoform. The catalytic unit of hOAT is the dimer. Enzyme residue Arg217 is an important hot-spot at the dimer-dimer interface of hOAT. The catalytic unit of hOAT is the dimer. The far-UV CD spectrum of the enzyme gives a secondary structure composition of 37% alpha-helix, 18% beta-sheet and 45% random coil, values identical to those calculated from the solved crystal structure, quaternary structure analysis, overview
additional information
-
apo and holo-hOAT enzymes (a) show a similar tertiary structure, even if apo displays a more pronounced exposure of hydrophobic patches, and (b) exhibit a tetrameric structure with a tetramer-dimer equilibrium dissociation constant about fivefold higher for the apoform with respect to the holoform. The catalytic unit of hOAT is the dimer. Enzyme residue Arg217 is an important hot-spot at the dimer-dimer interface of hOAT. The catalytic unit of hOAT is the dimer. The far-UV CD spectrum of the enzyme gives a secondary structure composition of 37% alpha-helix, 18% beta-sheet and 45% random coil, values identical to those calculated from the solved crystal structure, quaternary structure analysis, overview
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
the human enzyme is synthesized on cytoplasmic free ribosomes as a 45 kDa precursor and is processed into a mature protein after mitochondrial entry
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
complexed with 5-fluoromethylornithine, hanging drop vapor diffusion method
human OAT is crystallized as a recombinant protein obtained by expression of the entire gene in Escherichia coli, the packing of the dimers in the crystal yields a hexameric quaternary structure in which 3 dimers are arranged to form about one turn of a right-handed superhelix, OAT is also crystallized in the presence of L-canaline and gabaculine, co-crystallization of OAT with (2S, 5S)-5-fluoromethylornithine
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
E235A
mutant retains its regiospecificity for the gamma-amino group of ornithine, but the glutamate reaction is enhanced 650fold, whereas only a 5fold enhancement of the ketoglutarate reaction rate results
E235S
mutation leads to a lowering of the apparent rate and an increase of the dissociation constant
R180T
naturally occuring, gyrate atrophy-causing mutation of ornithine delta-aminotransferase (OAT), the R180T mutation involves an active site residue located at the dimer interface, which in the crystal structure of OAT complexed with 5-fluoromethylornithine engages a salt bridge with the alpha-carboxylate of the substrate analogue. the R180T mutant exhibits a remarkable loss of catalytic activity and is endowed with the ability to catalyse not only the delta-transamination but also, albeit to a lesser extent, the alpha-transamination of L-ornithine. The slight structural changes caused by the R180T mutation, preventing a proper collocation of L-ornithine at the active site of OAT, are responsible for the notable reduction of the catalytic efficiency. Enzyme mutant structure modelling, overview
R217A
site-directed mutagenesis, the artificial dimeric mutant variant exhibits spectroscopic properties, Tm values, and catalytic features similar to those of the tetrameric species. The mutant shows increased activity compared to wild-type
Y85I
mutation greatly affects the ketoglutarate reaction but has no effect on the glutamate reaction
G237D
-
patient with gyrate atrophy of the choroid and retina, mutation of both alleles, no enzymic activity in white blood cells. Son of patient is heterozygous for the mutation and has 45% of normal values for enzyme activity
Y85I
-
mutation of Tyr85 in human OAT to Ile decreases the rate of the reaction of the enzyme with ornithine 1000fold and increases that with 4-aminobutyrate 16fold, indicating that Tyr85 is a major determinant of specificity toward ornithine
additional information
additional information
overexpression of OAT promoting the growth and metastasis of A549 cells. OAT knockdown in H-1299 cells transfected with OAT siRNA results in a lower expression level of OAT mRNA and protein than in the control group. Knockdown of OAT suppresses cell proliferation, decreases the number of colonies, invades cells, and migrates cells
additional information
-
overexpression of OAT promoting the growth and metastasis of A549 cells. OAT knockdown in H-1299 cells transfected with OAT siRNA results in a lower expression level of OAT mRNA and protein than in the control group. Knockdown of OAT suppresses cell proliferation, decreases the number of colonies, invades cells, and migrates cells
additional information
-
transgenic mice that specifically overexpress human ornithine aminotransferase in the liver, kidneys and intestine exhibit higher enzyme activity in the liver than wild-type, but there are no differences in kinetic parameters between wild-type and transgenic animal. Ornithine aminotransferase overexpression decreases plasma and liver ornithine concentrations but does not affect glutamine or arginine homeostasis. There is an inverse relationship between ornithine levels and enzyme activity
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
67
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
unlike holo-hOAT, apo-hOAT is prone to unfolding and aggregation under physiological conditions. Under physiological conditions the apo-tetramer is slightly less prone to unfolding and aggregation than the apo-dimer
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, 50 mM potassium phosphate buffer, pH 8, 5 mM 2-oxoglutarate, 0.02 mM pyridoxal phosphate, 90-100% retention of activity after 1 month
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant enzyme 9.6fold from Escherichia coli strain BL21(DE3)pLysS by anion exchange chromatography, ultrafiltration, and gel filtration, followed by another step of ultrafiltration
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
it is believed that there is only one gene for OAT, pseudo-genes are not transcribed or lead to non-functional proteins, DNA and amino acid sequence comparisons and phylogenetic analysis, genetic organization and localization of OAT genes, overview
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
development of two new continuous, coupled assays for ornithine-delta-aminotransferase (OAT) that are more sensitive than previous methods, measure activity in real time, and can be carried out in multi-well plates for convenience and high throughput. The first assay is based on the reduction of DELTA1-pyrroline-5-carboxylate (P5C), generated from ornithine by OAT, using human pyrroline 5-carboxylate reductase 1, which results in the concomitant oxidation of NADH to NAD+. This procedure is three times more sensitive than previous methods, and is suitable for the study of small molecules as inhibitors or inactivators of OAT or as a method to determine OAT activity in unknown samples. The second method involves the detection of L-glutamate, produced during the regeneration of the cofactor PLP of OAT by an unamplified modification of the commercially available Amplex® Red L-glutamate detection kit (Life Technologies). This assay is recommended for the determination of the substrate activity of small molecules against OAT
diagnostics
OAT may be a potential biomarker for the diagnosis and therapeutic outcome monitoring of non-small cell lung cancer (NSCLC). Relationship between OAT mRNA expression and clinicopathological features in patients with NSCLC, overview
medicine
drug development
medicine
medicine
inhibition of OAT may represent a therapeutic strategy in treatment of non-small cell lung cancer (NSCLC)
drug development
-
human OAT as a potential target for development of new therapeutic drugs, OAT holds a significant scientific interest because of its association with gyrate atrophy, a recessive hereditary genetic dissorder leading to progressive loss of vision and eventually blindness in humans
drug development
-
human OAT is recognized as a potential target for chemotherapeutic drug development, in a study performed to evaluate the effect of selective blocking of mitosis in human cancer cells, OAT is identified as a protein, which binds the antimitotic drug diazonamide A and it has a role in regulating mitotic cell division
medicine
-
patient with gyrate atrophy of the choroid and retina, mutation G237D, responds to vitamin B6 medication
medicine
-
role in mitotic cell division and target for chemotherapeutic drug development
medicine
-
transgenic mice that specifically overexpress human ornithine aminotransferase in the liver, kidneys and intestine exhibit higher enzyme activity in the liver than wild-type, but there are no differences in kinetic parameters between wild-type and transgenic animal. Ornithine aminotransferase overexpression decreases plasma and liver ornithine concentrations but does not affect glutamine or arginine homeostasis. There is an inverse relationship between ornithine levels and enzyme activity
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Matsuzawa, T.; Sugimoto, N.; Sobue, M.; Ishiguro, I.
Ornithine oxoacid aminotransferase found in AH 130 ascites hepatoma cells
Biochim. Biophys. Acta
714
356-360
1982
Homo sapiens, Rattus norvegicus, Rattus norvegicus Wistar
Ohura, T.; Kominami, E.; Tada, K.; Katunuma, N.
Crystallization and properties of human liver ornithine aminotransferase
J. Biochem.
92
1785-1792
1982
Homo sapiens, Rattus norvegicus
Heinanen, K.; Nanto-Salonen, K.; Leino, L.; Pulkki, K.; Heinonen, O.; Valle, D.; Simell, O.
Gyrate atrophy of the choroid and retina: lymphocyte ornithine-d-aminotransferase activity in different mutations and carriers
Pediatr. Res.
44
381-385
1998
Homo sapiens
Roschinger, W.; Endres, W.; Shin, Y.S.
Characteristics of L-ornithine: 2-oxoacid aminotransferase and potential prenatal diagnosis of gyrate atrophy of the choroid and retina by first trimester chorionic villus sampling
Clin. Chim. Acta
296
91-100
2000
Homo sapiens, Rattus norvegicus
Seiler, N.
Ornithine aminotransferase, a potential target for the treatment of hyperammonemias
Curr. Drug Targets
1
119-153
2000
Homo sapiens, Rattus norvegicus
Shah, S.A.; Shen, B.W.; Brunger, A.T.
Human ornithine aminotransferase complexed with L-canaline and gabaculine: structural basis for substrate recognition
Structure
5
1067-1075
1997
Homo sapiens
Shen, B.W.; Hennig, M.; Hohenester, E.; Jansonius, J.N.; Schirmer, T.
Crystal structure of human recombinant ornithine aminotransferase
J. Mol. Biol.
277
81-102
1998
Homo sapiens
Storici, P.; Capitani, G.; Muller, R.; Schirmer, T.; Jansonius, J.N.
Crystal structure of human ornithine aminotransferase complexed with the highly specific and potent inhibitor 5-fluoromethylornithine
J. Mol. Biol.
285
297-309
1999
Homo sapiens (P04181), Homo sapiens
Ohkubo, Y.; Ueta, A.; Ito, T.; Sumi, S.; Yamada, M.; Ozawa, K.; Togari, H.
Vitamin B6-responsive ornithine aminotransferase deficiency with a novel mutation G237D
Tohoku J. Exp. Med.
205
335-342
2005
Homo sapiens
Markova, M.; Peneff, C.; Hewlins, M.J.; Schirmer, T.; John, R.A.
Determinants of substrate specificity in omega-aminotransferases
J. Biol. Chem.
280
36409-36416
2005
Homo sapiens (P04181)
Wang, G.; Shang, L.; Burgett, A.W.; Harran, P.G.; Wang, X.
Diazonamide toxins reveal an unexpected function for ornithine delta-amino transferase in mitotic cell division
Proc. Natl. Acad. Sci. USA
104
2068-2073
2007
Homo sapiens, Xenopus sp.
Ventura, G.; De Bandt, J.P.; Segaud, F.; Perret, C.; Robic, D.; Levillain, O.; Le Plenier, S.; Godard, C.; Cynober, L.; Moinard, C.
Overexpression of ornithine aminotransferase: consequences on amino acid homeostasis
Br. J. Nutr.
101
843-851
2009
Homo sapiens, Mus musculus
Dekaney, C.M.; Wu, G.; Yin, Y.L.; Jaeger, L.A.
Regulation of ornithine aminotransferase gene expression and activity by all-transretinoic acid in Caco-2 intestinal epithelial cells
J. Nutr. Biochem.
19
674-681
2008
Homo sapiens
Ravikumar, H.; Devaraju, K.; Shetty, K.
Effect of pH on spectral characteristics of P5C-ninhydrin derivative: Application in the assay of ornithine amino transferase activity from tissue lysate
Indian J. Clin. Biochem.
23
117-122
2008
Homo sapiens
Stranska, J.; Kopecny, D.; Tylichova, M.; Snegaroff, J.; Sebela, M.
Ornithine delta-aminotransferase: An enzyme implicated in salt tolerance in higher plants
Plant Signal. Behav.
3
929-935
2008
Cucurbita pepo, Homo sapiens, Nicotiana plumbaginifolia, Oryza sativa, Pisum sativum (B1A0U3), Vigna aconitifolia (P31893), Arabidopsis thaliana (Q9FNK4)
Ventura, G.; Moinard, C.; Segaud, F.; Le Plenier, S.; Cynober, L.; De Bandt, J.P.
Adaptative response of nitrogen metabolism in early endotoxemia: role of ornithine aminotransferase
Amino Acids
39
1417-1426
2010
Homo sapiens
Juncosa, J.I.; Lee, H.; Silverman, R.B.
Two continuous coupled assays for ornithine-delta-aminotransferase
Anal. Biochem.
440
145-149
2013
Homo sapiens (P04181)
Ginguay, A.; Cynober, L.; Curis, E.; Nicolis, I.
Ornithine aminotransferase, an important glutamate-metabolizing enzyme at the crossroads of multiple metabolic pathways
Biology
6
18
2017
Geukensia demissa, Oryctolagus cuniculus (A0A5F9CII4), Salmo trutta (A0A674DA32), Pisum sativum (B1A0U3), Homo sapiens (P04181), Rattus norvegicus (P04182), Mus musculus (P29758), Vigna aconitifolia (P31893), Bos taurus (Q3ZCF5), Plasmodium falciparum (Q6LFH8)
Montioli, R.; Paiardini, A.; Giardina, G.; Zanzoni, S.; Cutruzzola, F.; Cellini, B.; Borri Voltattorni, C.
R180T variant of delta-ornithine aminotransferase associated with gyrate atrophy biochemical, computational, X-ray and NMR studies provide insight into its catalytic features
FEBS J.
286
2787-2798
2019
Homo sapiens (P04181)
Zhu, W.; Doubleday, P.F.; Catlin, D.S.; Weerawarna, P.M.; Butrin, A.; Shen, S.; Wawrzak, Z.; Kelleher, N.L.; Liu, D.; Silverman, R.B.
A remarkable difference that one fluorine atom confers on the mechanisms of inactivation of human ornithine aminotransferase by two cyclohexene analogues of gamma-aminobutyric Acid
J. Am. Chem. Soc.
142
4892-4903
2020
Homo sapiens (P04181), Homo sapiens
Liu, Y.; Wu, L.; Li, K.; Liu, F.; Wang, L.; Zhang, D.; Zhou, J.; Ma, X.; Wang, S.; Yang, S.
Ornithine aminotransferase promoted the proliferation and metastasis of non-small cell lung cancer via upregulation of miR-21
J. Cell. Physiol.
234
12828-12838
2019
Homo sapiens (P04181), Homo sapiens
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