Information on EC 6.3.4.5 - Argininosuccinate synthase

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea

EC NUMBER
COMMENTARY hide
6.3.4.5
-
RECOMMENDED NAME
GeneOntology No.
Argininosuccinate synthase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + L-citrulline + L-aspartate = AMP + diphosphate + 2-(Nomega-L-arginino)succinate
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
amination
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Alanine, aspartate and glutamate metabolism
-
-
Arginine biosynthesis
-
-
Biosynthesis of antibiotics
-
-
Biosynthesis of secondary metabolites
-
-
canavanine biosynthesis
-
-
L-arginine biosynthesis I (via L-ornithine)
-
-
L-arginine biosynthesis II (acetyl cycle)
-
-
L-arginine biosynthesis III (via N-acetyl-L-citrulline)
-
-
L-arginine biosynthesis IV (archaebacteria)
-
-
L-citrulline-nitric oxide cycle
-
-
Metabolic pathways
-
-
urea cycle
SYSTEMATIC NAME
IUBMB Comments
L-Citrulline:L-aspartate ligase (AMP-forming)
-
CAS REGISTRY NUMBER
COMMENTARY hide
9023-58-9
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
UniProt
Manually annotated by BRENDA team
antimonial-sensitive and antimonial-resistant strains
UniProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
strain 1278b, mutant MG409
-
-
Manually annotated by BRENDA team
strain 1278b, mutant MG409
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + citrulline + aspartate
AMP + diphosphate + 2-(Nomega-L-arginino)succinate
show the reaction diagram
ATP + L-citrulline + 3-nitro-2-aminopropanoate
?
show the reaction diagram
-
60% of the maximal activity with Asp
-
-
-
ATP + L-citrulline + L-Asp
?
show the reaction diagram
ATP + L-citrulline + L-Asp
AMP + diphosphate + L-argininosuccinate
show the reaction diagram
ATP + L-citrulline + L-aspartate
AMP + diphosphate + 2-(Nomega-L-arginino)succinate
show the reaction diagram
ATP + L-citrulline + L-aspartate
AMP + diphosphate + L-argininosuccinate
show the reaction diagram
ATP + L-citrulline + threo-beta-hydroxy-DL-Asp
?
show the reaction diagram
-
-
-
-
-
ATP + L-citrulline + threo-beta-methyl-L-Asp
?
show the reaction diagram
-
-
-
-
-
dATP + L-citrulline + L-Asp
dAMP + diphosphate + L-argininosuccinate
show the reaction diagram
-
2.6% as active as ATP
-
-
-
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + L-citrulline + L-Asp
?
show the reaction diagram
ATP + L-citrulline + L-Asp
AMP + diphosphate + L-argininosuccinate
show the reaction diagram
ATP + L-citrulline + L-aspartate
AMP + diphosphate + 2-(Nomega-L-arginino)succinate
show the reaction diagram
ATP + L-citrulline + L-aspartate
AMP + diphosphate + L-argininosuccinate
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,2-Cyclohexanedione
-
magnesiumdiphosphate and analogues protect
2,3-Butanedione
-
magnesiumdiphosphate and analogues protect
2-aminopentanoic acid
-
competitive to L-citrulline
5,5'-dithiobis(2-nitrobenzoate)
-
-
ADP
-
-
alpha-methyl-D,L-aspartate
-
-
CTP
-
slight
D-Asp
-
-
dGTP
-
slight
diphosphate
-
-
diphosphoryl lipid A (DPL)
-
DPL from Escherichia coli, inhibits argininosuccinate synthetase in a dose-dependent manner, concentration for half inhibition of argininosuccinate synthetase enzyme activity: 0.039 mg/ml
-
dTTP
-
slight
erythro-3-Hydroxy-3-methylaspartate
-
-
Glyoxal
-
magnesiumdiphosphate and analogues protect
GTP
-
slight
IL-1beta
-
a long-term 24 h exposure of ASS to IL-1beta in Caco-2 cells inhibits its activity. The inhibiting effect of IL-1beta is linked to the production of nitric oxide (NO) induced by IL-1beta. The inhibiting effect is totally blocked in the presence of N-methyl-L-arginine an inhibitor of the inducible nitric oxide synthase or by culturing the cells in an arginine-deprived medium
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L-argininosuccinate
L-Ile
-
competitive to L-citrulline
L-norvaline
L-Val
-
competitive to L-citrulline
methyl-DL-aspartic acid
at 1 mM methyl-DL-aspartic acid the enzyme activity is reduced by about 60%, while at 5 mM the catalytic activity is completely abolished
-
Methylaspartate
-
-
monophosphoryl lipid A (MPL)
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MPL from Escherichia coli, inhibits argininosuccinate synthetase in a dose-dependent manner, concentration for half inhibition of argininosuccinate synthetase enzyme activity: 0.270 mg/ml
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NO
-
mediates reversible S-nitrosylation and inactivation of argininosuccinate synthetase in vitro and in lipopolysaccharide-treated cells and mice. S-nitrosylation of Cys132 is noth necessary and sufficient for the inhibition of argininosuccinate synthase by NO donors
p-chloromercuribenzoate
-
-
Phenylglyoxal
phosphate
-
competitive with respect to citrulline and Asp
R-lipopolysaccharide (LPS)
-
rough-type LPS from Escherichia coli, inhibits argininosuccinate synthetase in a dose-dependent manner, concentration for half inhibition of argininosuccinate synthetase enzyme activity: 0.230 mg/ml
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recombinant mycoplasma arginine deiminase
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36% decrease in AS activity after rADI treatment
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S-lipopolysaccharide (LPS)
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smooth-type-LPS from Escherichia coli, inhibits argininosuccinate synthetase in a dose-dependent manner, concentration for half inhibition of argininosuccinate synthetase enzyme activity: 0.024 mg/ml
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sodium 2-deoxy-2-(3S-(9-phenyl-nonanoyl-oxy) tetradecanoyl) amino-3-O-(9-phenyl-nonanoyl)-D-glucopyranose 4-sulfate
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synthesized lipid A analog, inhibits argininosuccinate synthetase in a dose-dependent manner, concentration for half inhibition of argininosuccinate synthetase enzyme activity: 0.0065 mg/ml
threo-3-Hydroxy-3-methylaspartate
-
-
UTP
-
slight
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
IL-1beta
-
ASS is rapidly induced by a short time exposure of IL-1beta to Caco-2 cells. By contrast, a long-term 24 h exposure to IL-1beta inhibited the ASS activity despite an increase in both specific mRNA-level and protein amount, demonstrating a post-translational effect
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lipopolysaccharide
recombinant mycoplasma arginine deiminase
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350% increase in AS activity in HeLa cells after rADI treatment, no activity change in umbilical vein endothelial cells
-
additional information
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.022
AMP
0.12
argininosuccinate
-
-
0.017 - 4.3
Asp
0.12 - 0.18
aspartate
0.041 - 0.66
ATP
0.02 - 190
citrulline
0.016
diphosphate
0.025 - 0.038
L-Asp
0.026 - 0.03
L-citrulline
4.5
threo-beta-hydroxy-L-Asp
-
-
0.88
threo-beta-methyl-L-Asp
-
-
additional information
additional information
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.25
L-arginine
-
pH 8.7, 70C
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
additional information
Mus musculus
-
substrate: diphosphoryl lipid A, IC50: 0.039 mg/ml; substrate: monophosphoryl lipid A, IC50: 0.270 mg/ml; substrate: R-lipopolysaccharide, IC50: 0.230 mg/ml; substrate: S-lipopolysaccharide, IC50: 0.024 mg/ml; substrate: sodium 2-deoxy-2-(3S-(9-phenyl-nonanoyl-oxy) tetradecanoyl) amino-3-O-(p-phenyl-nonanoyl)-D-glucopyranose 4-sulfate (ONO-4007), IC50: 0.0065 mg/ml
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.000001
-
37C, cell homogenate
0.000006
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37C, A-549 cell homogenate
0.000013
-
37C, LNCaP cell homogenate
0.000019
-
37C, MCF-7 cell homogenate
0.000048
-
37C, HeLa cell homogenate
0.000174
-
37C, cell homogenate
0.0002
-
pH 8.7, 70C, activity in cell culture in growth medium 0.5% peptone and 0.1% yeast extract
0.00045
-
pH 8.7, 70C, activity in cell culture in growth medium with 0.2% yeast extract
0.0007
-
pH 8.7, 70C, activity in cell culture in minimal growth medium with 20 mM glucose and 5 mM NH4+
0.002
-
in the presence of 5 mM (NH4)2SO4 and after addition of 20 mM L-norvaline in root-free compartments
0.0028
-
in the presence of 5 mM (NH4)2SO4 and after addition of 20 mM L-norvaline in the root-free compartments
0.0071
-
in the presence of 5 mM (NH4)2SO4 and after addition of 0.5 mM phenyl phosphorodiamidate in root-free compartments
0.0085
-
in the presence of 5 mM (NH4)2SO4 in root-free compartments
0.0166
0.049
-
in the presence of 5 mM (NH4)2SO4 and after addition of 0.5 mM phenyl phosphorodiamidate in the root-free compartments; in the presence of 5 mM (NH4)2SO4 in the root-free compartments
0.14
-
purification step: liver homogenate supernatant
0.27
-
purification step: 45-55% saturated ammonium sulfate precipitate
0.95
-
-
0.99
-
purification step: DE-52 fraction
1
-
specific activity of ASS in Caco-2 cells after long time exposure (24h) to 1 ng/ml IL-1beta
1.27
-
specific activity of ASS in Caco-2 cells after the addition of 0.5 mM S-nitroso-acetylpenicillamine for 24h, an NO donor. This clearly demonstrates that NO induces an inhibition of the ASS activity in Caco-2 cells.
1.3
-
-
1.39
-
purification step: S-300 fraction
2.5
-
specific activity of ASS in Caco-2 cells after short time exposure (4h) to 1 ng/ml IL-1beta
3.8
-
-
3.83
-
-
4.2
-
-
5.16
-
purification step: UNO S-1 fraction
12.8
-
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6
-
reaction of AMP + diphosphate + L-argininosuccinate
6 - 6.5
-
reaction of AMP + diphosphate + L-argininosuccinate
6.2 - 6.3
-
reaction of AMP + diphosphate + L-argininosuccinate
7.5 - 7.8
-
reaction of ATP + citrulline + L-argininosuccinate
8.4 - 8.8
-
-
8.4
-
reaction of ATP + citrulline + L-Asp
8.6
-
reaction of ATP + citrulline + L-Asp, enzyme forms ASSI and ASSII
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.5 - 7
-
about 60% of maximal activity at pH 5.5 and 7
6.5 - 8.5
-
6.5: about 55% of maximal activity, 8.5: about 70% of maximal activity, reaction of ATP + citrulline + L-argininosuccinate
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.8
calculated from amino acid sequence
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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human adenocarcinoma cell line Caco-2/TC7
Manually annotated by BRENDA team
more abundantly expressed in amastigotes than in promastigotes
Manually annotated by BRENDA team
-
pancreatic cancer cell line, low ASS expression level
Manually annotated by BRENDA team
Northern analyses of ass during fruiting body formation and post-harvest development reveals that expression is significantly up-regulated from developmental stage 3 on for all the tissues studied (gills, stip and cap). The expression reaches a maximum at the later stages of fruiting body growth, stages 6 and 7
Manually annotated by BRENDA team
-
pancreatic cancer cell line, low ASS expression level
Manually annotated by BRENDA team
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in a rat ischemia model the striatum is examined at 24, 72 and 144 h after reperfusion and compared with rats in normal conditions. At 24 h after reperfusion, the number of the nitric oxide synthase-positive neurons and the percentage of those co-expressing argininosuccinate synthetase and argininsuccinate lyase and nitric oxide synthase are significantly increased in the animals with a longer survival
Manually annotated by BRENDA team
-
expression analysis is performed in bovine aortic endothelial cells (BAEC)
Manually annotated by BRENDA team
Northern analyses of ass during fruiting body formation and post-harvest development reveals that expression is significantly up-regulated from developmental stage 3 on for all the tissues studied (gills, stip and cap). The expression reaches a maximum at the later stages of fruiting body growth, stages 6 and 7
Manually annotated by BRENDA team
-
pancreatic cancer cell line, low ASS expression level
Manually annotated by BRENDA team
-
pancreatic cancer cell line, low ASS expression level
Manually annotated by BRENDA team
-
a human hepatoma cell line
Manually annotated by BRENDA team
-
parental cell line MGL8B2 and canavanine-resistant cell line MGL8D1
Manually annotated by BRENDA team
-
pancreatic cancer cell line, very low ASS expression level
Manually annotated by BRENDA team
-
extraradical myecelium
Manually annotated by BRENDA team
-
increased co-expression of AS and TNF-a mRNA is observed in non-small cell lung and stomach cancer, compared with normal corresponding tissues
Manually annotated by BRENDA team
-
AS mRNA increases 2- to 3fold by 24 h in both the IGROV-1 cell line, and a second ovarian cancer cell line OVCAR-3, following treatment with TNF-alpha. In contrast, although the ovarian cancer cell lines, PEO1 and SKOV-3, express AS in abundance, this is not TNF-a-inducible; TNF-alpha induces prolonged expression of AS mRNA and protein in ovarian tumour cells, contrasting with short-lived expression of AS mRNA in the normal ovarian epithelial cells. AS mRNA is higher expressed in ovarian tumor tissue compared to normal ovarian tissue. Moreover, AS protein colocalises with TNF-alpha in ovarian cancer cells, with significantly higher levels of AS in malignant compared with normal ovarian tissue.
Manually annotated by BRENDA team
-
pancreatic cancer cell line, very low ASS expression level
Manually annotated by BRENDA team
-
pancreatic cancer cell line, low ASS expression level
Manually annotated by BRENDA team
-
AM roots
Manually annotated by BRENDA team
-
a human epithelium cell line
Manually annotated by BRENDA team
-
argininosuccinate synthase accumulates in circulation within 1 h after treatment with both lipopolysaccharide alone and hepatotoxic combination of lipopolysaccharide and D-Galactosamine
Manually annotated by BRENDA team
Northern analyses of ass during fruiting body formation and post-harvest development reveals that expression is significantly up-regulated from developmental stage 3 on for all the tissues studied (gills, stip and cap). The expression reaches a maximum at the later stages of fruiting body growth, stages 6 and 7
Manually annotated by BRENDA team
-
increased co-expression of AS and TNF-a mRNA is observed in non-small cell lung and stomach cancer, compared with normal corresponding tissues
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
only a small proportion of the total cellular enzyme is localized in vesicles
Manually annotated by BRENDA team
additional information
-
at the activity level, the colocation of argininosuccinate synthetase is changing during fetal and neonatal developement and is under the control of corticosteroid and pancreatic hormones
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
UNIPROT
Campylobacter jejuni subsp. jejuni serotype O:2 (strain ATCC 700819 / NCTC 11168)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
45000
-
SDS-PAGE
46000
SDS-PAGE
47270
deduced from cDNA
48500
deduced from cDNA
80000
-
gel filtration
158000
-
gel filtration
175000
-
gel filtration
180000
-
gel filtration
183000
-
gel filtration
185000
207000
-
sedimentation equilibrium centrifugation
228000
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
-
2 * 45000, SDS-PAGE under reducing and nonreducing conditions
homotetramer
tetramer
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
nitrosylation
-
exposure of ASS to IL-1beta in Caco-2 cells induces the nitrosylation of the ASS protein
phosphoprotein
-
regulation of argininosuccinate synthase by dynamic phosphorylation through protein kinase A, the enzyme lacks a consensus Akt phosphorylation motif R-X-R-X-X-S/T
additional information
-
it is shown that IL-1beta inhibits the ASS activity through a post-translational mechanism since increase in both specific mRNA-level and protein amount can be detected after long-time exposure of Caco-2 cells to IL-1beta. The inhibiting effect of IL-1beta is linked to the production of nitric oxide (NO) induced by IL-1beta
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
crystal strucures in complex with intact ATP and with ATP and citrulline, hanging drop vapour-diffusion technique, X-ray analysis
-
recombinant EAS, hanging drop vapour-diffusion technique, X-ray analysis
-
purified recombinant ASS1 by hanging-drop method, 0.001 ml of protein solution containing 17 mg/ml protein in 500 mM NaCl, 2 mM TCEP, 30 mM HEPES, pH 7.5, 10 mM aspartate, and 10 mM citrulline, is mixed with 0.001 ml of reservoir solution containing 16% w/v PEG 3350, 0.15 M dl-malic acid pH 7.0, X-ray diffraction structure determination and analysis at 2.4-2.5 A resolution
3-dimensional structure of free enzyme and of complexes with intact ATP, adenylyl imidodiphosphate, arginine or succinate, hanging drop method
-
structures of enzyme complexed with intact ATP and substrates citrulline and aspartate, complexed with AMP and argininosuccinate, and complexed with AMP-PNP, arginine, aspartate and Mg2+, vapor diffusion method, X-ray analysis
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
45
-
enzyme forms ASSI and II are stable, enzyme form ASSIII is very unstable
50
-
7 min, enzyme from normal liver and from patients with citrullinemia, in presence of 10 mM argininosuccinate, about 10% loss of activity; 7 min, enzyme from normal liver, in absence of argininosuccinate, about 65% loss of activity; 7 min, enzyme from patients with citrullinemia, in absence of argininosuccinate, 95% loss of activity
additional information
-
argininosuccinate stabilizes against heat treatment
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
argininosuccinate stabilizes against heat treatment
-
in presence of 5 mM argininosuccinate, the activities of the three forms of the enzyme are resistant to chymotrypsin
-
unstable during purification
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20C, 0.05 M citrulline, 0.05 M Asp, or 0.01 M argininosuccinate, stable for more than 1 year
-
-20C, stable for months
-
-70C, stable for 3 months
-
0-4C, without (NH4)2SO4, stable for about 2 weeks
-
quite stable frozen or as ammonium sulfate precipitate
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
3 enzyme forms ASSI, ASSII, and ASSIII
-
affinity chromatography
analysis by native gel electrophoresis shows that argininosuccinate synthetase can bind bacterial lipopolysaccharide and lipid A; argininosuccinate synthetase is purified from mouse liver. Livers are excised from 20 male mice (C3H/He strain, age 7-8 weeks) and homogenized in 100 mM Tris-HCl (pH 7.5) containing 1 mM citrulline and 1 mM aspartic acid. Homogenate is centrifuged. After salting-out with (NH4)2SO4. The sample is subjected to anion-exchange chromatography on DE-52. Concentrated samples are loaded on a column of Sephacryl S-300 HR. The collected first peak fractions are dialyzed and subjected to anion-exchange chromatography on UNO S-1
-
Ni-NTA agarose column chromatography
recombinant
-
recombinant ASS1 by His affinity chromatography and gel filtration
recombinant EAS
-
recombinant His-tagged enzyme from Escherichia coli by nickel affinty chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cloned in Escherichia coli
expressed as a C-terminal fusion protein with maltose-binding protein in Escherichia coli
-
expressed in Escherichia coli BL21 (DE3) pLysS cells
expression alone or together with FLAG-tagged HSCARG or with HSCARG siRNA in HeLa and HEK-293 cells, expression analysis, overview
-
expression analysis, the AS gene promoter contains a a near consensus PPARgamma response element, PPRE, overview
-
expression in Escherichia coli
expression in Escherichia coli as fusion protein with maltose binding protein
-
expression in Escherichia coli BB101
-
expression in Escherichia coli BL21(DE3)pLysE
expression of ASS1
expression of the His-tagged enzyme in Escherichia coli
-
overexpression in Escherichia coli
-
the gene encoding argininosuccinate synthetase of Porphyra yezoensis is obtained by PCR using an expressed sequence tag clone as a template, and subcloned into the yeast expression vector pYES2. The gene is expressed when the vector harboring PyARG1 is introduced into an ARG1-deficient strain of Saccharomyces cerevisiae, which results in complementation of the mutant phenotype. The transformed cells survive on a selective medium lacking arginine, and transcripts of PyARG1 are detected by RT-PCR. A quantitative comparison shows that the rescued mutant cells grow in the selective liquid medium with a minor reduction in growth rate relative to wild-type cells
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
downregulation of enzyme expression is associated with the development of platinum resistance to platinum-based drugs
-
hepatic argininosuccinate synthase expression is hormonally regulated, expression of endothelial and inflammatory cell argininosuccinate synthase is under control of cytokines
-
increased expression in drug resistant mutant
overexpression of argininosuccinate synthase in primary ovarian, stomach and colorectal cancer cells results in platinum sensitive tumours
-
threefold repression of enzyme formation by arginine
tumoural enzyme downregulation by hepatocellular carcinoma, malignant melanoma, malignant pleural mesothelioma, prostate and renal cancer
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
A192V
-
mutant G280R has no ASS activity, mutants A192V, R272C, and R304W have low ASS activity and abnormal kinetics. A higher Km for citrulline than in wild-type enzyme is obtained with mutants A192V, R272C, and R304W
D296G
-
mutation of the argininosuccinate synthetase gene, found in patients
E191Q
-
mutation of the argininosuccinate synthetase gene, found in patients
G1168A
-
mutation results in citrullinemia type I
G156del
-
mutation of the argininosuccinate synthetase gene, found in patients
G280R
-
mutant G280R has no ASS activity, mutants A192V, R272C, and R304W have low ASS activity and abnormal kinetics. A higher Km for citrulline than in wild-type enzyme is obtained with mutants A192V, R272C, and R304W
G324V
-
mutation of the argininosuccinate synthetase gene, found in patients
G347R
-
mutation of the argininosuccinate synthetase gene, found in patients
K277T
-
mutation of the argininosuccinate synthetase gene, found in patients
L160P
-
mutation of the argininosuccinate synthetase gene, found in patients
L206P
-
mutation of the argininosuccinate synthetase gene, found in patients
N158del
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mutation of the argininosuccinate synthetase gene, found in patients
P96H
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mutation of the argininosuccinate synthetase gene, found in patients
Q311del
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mutation of the argininosuccinate synthetase gene, found in patients
Q401del
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mutation of the argininosuccinate synthetase gene, found in patients
R127Q
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mutation of the argininosuccinate synthetase gene, found in patients
R127W
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mutation of the argininosuccinate synthetase gene, found in patients
R265C
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mutation of the argininosuccinate synthetase gene, found in patients
R272C
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mutant G280R has no ASS activity, mutants A192V, R272C, and R304W have low ASS activity and abnormal kinetics. A higher Km for citrulline than in wild-type enzyme is obtained with mutants A192V, R272C, and R304W
R304W
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mutant G280R has no ASS activity, mutants A192V, R272C, and R304W have low ASS activity and abnormal kinetics. A higher Km for citrulline than in wild-type enzyme is obtained with mutants A192V, R272C, and R304W
R344del
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mutation of the argininosuccinate synthetase gene, found in patients
S341F
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mutation of the argininosuccinate synthetase gene, found in patients
S79P
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mutation of the argininosuccinate synthetase gene, found in patients
T284I
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mutation of the argininosuccinate synthetase gene, found in patients
Y291S
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mutation of the argininosuccinate synthetase gene, found in patients
Y359D
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mutation of the argininosuccinate synthetase gene, found in patients
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
drug development
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high levels of AS expression, which may be required for several arginine-dependent processes in cancer, including the production of nitric oxide, proline, pyrimidines and polyamines, is regulated by TNF-alpha and may provide an important molecular pathway linking inflammation and metabolism to ovarian tumorigenesis
medicine
molecular biology
report in which the function of a Porphyra yezoensis gene has been directly demonstrated by the rescue of a Saccharomyces cerevisiae mutant. This technique may provide new opportunities for further investigations into the functions of various genes in Porphyra yezoensis and other macroalgal species
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