Information on EC 2.1.3.2 - aspartate carbamoyltransferase

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

EC NUMBER
COMMENTARY hide
2.1.3.2
-
RECOMMENDED NAME
GeneOntology No.
aspartate carbamoyltransferase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
carbamoyl phosphate + L-aspartate = phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
carbamoyl group transfer
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Alanine, aspartate and glutamate metabolism
-
-
Metabolic pathways
-
-
pyrimidine metabolism
-
-
Pyrimidine metabolism
-
-
UMP biosynthesis
-
-
SYSTEMATIC NAME
IUBMB Comments
carbamoyl-phosphate:L-aspartate carbamoyltransferase
-
CAS REGISTRY NUMBER
COMMENTARY hide
9012-49-1
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
mussel
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
Pigeon
-
-
-
Manually annotated by BRENDA team
biovar B
-
-
Manually annotated by BRENDA team
Pseudomonas vulgaris
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
strain 2693 isolated from the deep atlantic
-
-
Manually annotated by BRENDA team
strain 2693 isolated from the deep atlantic
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
-
2 types of the enzyme occur: a CPSII-DHO-ATC fusion enzyme (CAD) found in animals, fungi, and amoebozoa, where the enzymes carbamoylphosphate synthetase II (CPSII), aspartate transcarbamoylase (ATC), and dihydroorotase (DHO), catalyzing the first three reaction steps of the de novo pyrimidine biosynthetic pathway, form a complex, and (2) stand-alone enzymes found in plants and the protist groups
malfunction
analysis of the conformational changes shows that there is a lack of cooperativity in trimeric ATCases that do not possess regulatory subunits
metabolism
physiological function
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
carbamoyl phosphate + L-asparagine
phosphate + N-carbamoyl-L-asparagine
show the reaction diagram
-
the enzyme catalyzes the carbamoylation of L-Asn with a Km of 122 mM and a maximal velocity 10fold lower than observed with the natural substrate, L-Asp. As opposed to L-Asp, no cooperativity is observed with respect to L-Asn
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
L-aspartate + carbamoyl phosphate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
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
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
L-aspartate + carbamoyl phosphate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
dATP
-
stimulates
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Mg2+
-
required for synergistic inhibition of the enzyme by CTP and UTP, metal binding site in the allosteric regulatory site of ATCase, overview
additional information
-
no requirement for any metal ion
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(2S)-2-(([hydroxy(hydroxymethyl)phosphoryl]acetyl)amino)butanedioic acid
-
competitive
(2S)-2-(([hydroxy(oxido)-lambda5-phosphanyl]acetyl)amino)butanedioic acid
-
competitive
2,2-dimethylsuccinate
-
-
2-(4-hydroxy-2,4-dioxo-4lamdba5-[1,4]azaphosphinan-1-yl)-succinic acid
-
competitive
2-methylquinazolin-4(3H)-one
-
-
2-phenyl-1,3-4(H)benzothiazin-4-thione
-
noncompetitive inhibitor towards both aspartate and carbamoyl phosphate
2-ThioUMP
-
-
3-amino-6,8-dibromo-2-methyl-4(3H)-quinazolinone
-
-
3-amino-6,8-dibromo-2-phenyl-4-(3H)-quinazolinone
-
noncompetitive
4,5-dicarboxy-2-ketopentylphosphonate
-
-
5'-UMP
-
2'-UMP and 3'-UMP have no effect
acetate
-
-
acetyl phosphate
aspartate
carbamoyl aspartate
Carbamoylaspartate
-
-
Carbonyldiphosphonate
-
-
Cu2+
-
strong inhibition
cytidine
-
-
dichlormethylenediphosphonate
-
-
diphosphate
Diphosphate analogues
-
-
-
fumarate
-
-
Guanidine-HCl
-
800 mM, almost complete inhibition
HgCl2
-
0.001 mM, 50% inhibition
hypophosphate
-
-
imidodiphosphonate
-
-
Inosine
-
-
iodoacetate
ITP
-
weak inhibition
L-aspartate
-
-
L-Malate
-
-
Maleate
Mersalyl
-
0.01 mM, 50% inhibition
mesotartrate
-
-
Methylenediphosphonate
-
-
N-(2-hydroxy-acetyl)-L-aspartic acid-phosphate
-
competitive
N-(phosphonacetyl)-L-aspartate
N-(Phosphonoacetyl)-L-aspartate
N-(phosphonoacetyl)-L-aspartic acid
-
-
N-Diphosphoryl-L-aspartate
-
-
N-methyl phosphonoacetamide
-
-
N-phosphonacetyl-L-asparagine
-
potent inhibitor of ATCase
N-phosphonacetyl-L-aspartate
N-phosphonoacetyl-L-aspartate
N-phosphoryl-L-aspartate
-
-
N-pyrophosphoryl-L-aspartate
-
-
nucleotides
O-phosphonoacetyl-oxosuccinate
-
-
p-chloromercuribenzoate
p-hydroxymercuribenzoate
p-mercuribenzoate
-
0.01 mM, 50% inhibition
Phenylglyoxal
-
-
phosphate
phosphonoacetamide
-
-
Phosphonoacetate
-
-
phosphonoacetic acid arsenate
Phosphonoformate
-
-
phosphonopropionate
-
-
S-diphosphoryl-mercaptosuccinate
-
-
S-phosphonoacetyl-mercaptosuccinate
-
-
succinate
Urea
-
2.5 M, almost complete inhibition
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
4-aminobutyrate
acetate
-
25 mM, 2.3fold activation
adenosine
-
very weak activation
Aminoethanol
-
activates
beta-Alanine
-
600% activation
Butyrate
Carbamoyl-beta-alanine
D-Aspartate
-
5700% activation
dimethyl sulfoxide
-
strong stimulation
dimethylformamide
-
-
dimethylsulfamide
-
-
formate
GTP
holoenzyme, catalytic subunits alone are inhibited
Hydroxylamine-HCl
-
30 mM, 2120% activation
Imidazole-HCl
-
30 mM, 2710% activation
Isobutyrate
L-2-aminobutyrate
L-alanine
-
800% activation
L-Malate
-
activation in presence of excess carbamoyl phosphate and limiting L-aspartate
mesotartrate
-
activation in presence of excess carbamoyl phosphate and limiting L-aspartate
N,N-dimethylmethanamide
-
strong stimulation
N-(Phosphonoacetyl)-L-aspartate
N-phosphonacetyl-L-aspartate
NaCl
-
30 mM, 1730% activation
NH4Cl
-
30 mM, 2710% activation
Propionate
succinate
Triethanolamine-HCl
-
30 mM, 1950% activation
Tris-HCl
-
30 mM, 2620% activation
additional information
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
7
aspartate
-
-
0.004 - 88
Carbamoyl phosphate
162
Carbamoylphosphate
-
at 37C
122
L-asparagine
-
-
0.009 - 44.7
L-aspartate
additional information
additional information
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
79.7
aspartate
Mesocricetus auratus
-
aspartate transcarbamoylase activity domain of the multienzyme complex
35.9 - 47.2
Carbamoyl phosphate
57.4
Carbamoylphosphate
Mesocricetus auratus
-
multienzyme complex
5.6 - 417
L-aspartate
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000193
(2S)-2-(([hydroxy(hydroxymethyl)phosphoryl]acetyl)amino)butanedioic acid
-
-
0.000417
(2S)-2-(([hydroxy(oxido)-lambda5-phosphanyl]acetyl)amino)butanedioic acid
-
-
2.2
2,2-dimethylsuccinate
-
inhibition of catalytic subunits, C3
0.001
2-(4-hydroxy-2,4-dioxo-4lamdba5-[1,4]azaphosphinan-1-yl)-succinic acid
-
catalytic subunit of aspartate transcarbamoylase
7.5
3-phosphonopropanoic acid
-
-
0.00001
4,5-dicarboxy-2-ketopentylphosphonate
-
-
80
aspartate
-
substrate inhibition, complex of catalytic subunits, C3
0.0085
ATP
7 - 15
carbamoyl aspartate
13
Carbamoylaspartate
-
noncompetitive vs. carbamoyl phosphate
0.0035
Carbonyldiphosphonate
-
-
0.1
CDP
1.1
chloride
-
inhibition of catalytic subunits, C3
0.007 - 0.037
CTP
0.032
dichlormethylenediphosphonate
-
-
0.0004 - 0.9
diphosphate
2
ethylamidocarbonylphosphonate
-
-
-
5.3
fumarate
-
inhibition of catalytic subunits, C3
0.02
hypophosphate
-
-
0.071
imidodiphosphonate
-
-
4.59 - 13.56
L-aspartate
0.17 - 1
Maleate
0.7
mesotartrate
-
inhibition of catalytic subunits, C3
0.037
Methylenediphosphonate
-
-
0.00021
N-(2-hydroxy-acetyl)-L-aspartic acid-phosphate
-
catalytic subunit of aspartate transcarbamoylase
0.000001 - 0.000027
N-(phosphonacetyl)-L-aspartate
0.000006
N-(Phosphonoacetyl)-L-aspartate
-
-
1.54
N-methyl phosphonoacetamide
-
-
0.000016
N-phosphonoacetyl-L-aspartate
-
-
0.05
N-phosphoryl-L-aspartate
-
-
0.00024
N-pyrophosphoryl-L-aspartate
-
-
0.002
O-phosphonoacetyl-oxosuccinate
-
-
0.175
peroxydiphosphonate
-
-
-
0.1 - 14
phosphate
0.66
phosphonoacetamide
-
-
0.15
Phosphonoacetate
-
-
0.022
Phosphonoformate
-
-
1.5
ribose-5-P
0.017
S-diphosphoryl-mercaptosuccinate
-
-
0.0055
S-phosphonoacetyl-mercaptosuccinate
-
-
1.6 - 3.5
succinate
0.00049
UMP
-
-
0.0085
UTP
additional information
additional information
-
Ki-values at varying concentrations of Asp and carbamoyl phosphate
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.2
2-methylquinazolin-4(3H)-one
Mus musculus
-
-
0.15
2-phenyl-1,3-4(H)benzothiazin-4-thione
Mus musculus
-
-
0.35
3-amino-6,8-dibromo-2-methyl-4(3H)-quinazolinone
Mus musculus
-
-
0.18
3-amino-6,8-dibromo-2-phenyl-4-(3H)-quinazolinone
Mus musculus
-
-
0.000055
N-(phosphonoacetyl)-L-aspartic acid
Escherichia coli
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4.5
-
30C, presence of 5 mM ATP
6
-
30C, presence of 5 mM GTP
6.1
-
30C, presence of 5 mM UTP
6.7
-
30C, presence of 5 mM ADP
6.8
-
30C, presence of 5 mM diphosphate
8
-
30C, presence of 5 mM UDP
8.4
-
30C, presence of 5 mM UMP
9
-
30C, presence of 5 mM CTP
11.4
-
30C, presence of 5 mM CDP
11.8
-
30C, presence of 5 mM GDP
22.3
-
30C, presence of 5 mM GMP
22.4
-
30C, presence of 5 mM AMP
25.9
-
30C, presence of 5 mM phosphate
32.8
-
30C, presence of 5 mM CMP
148.3
-
recombinant enzyme
238.3
-
recombinant enzyme, overexpressed in E. coli
333
-
recombinant enzyme, in the presence of 50 mM Tris-acetate
450
-
recombinant enzyme
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5
-
assay at
8.2
-
presence of high concentration of L-aspartate
9 - 10
-
-
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7 - 8.5
-
steep increase in activity until pH 8.5, decrase above
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25
-
assay at
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
2 - 50
-
20% of maximal activity at 2C, 30% at 6C
30 - 75
-
approx. 70% of maximal activity at 30C, approx. 30% of maximal activity at 75C
additional information
-
the wild-type enzyme shows o change in structure by SAXS through the temperature range of 4C to 55C, whereas the D236A ATCase exhibits a large shift toward the T state between 4C and 30C, with a minor shift back toward the R state between 30C and 45C
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
markedly increased expression of PYRB in root tissues during the first 5 days after germination
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
PDB
SCOP
CATH
ORGANISM
UNIPROT
Bacillus subtilis (strain 168)
Bacillus subtilis (strain 168)
Bacillus subtilis (strain 168)
Bacillus subtilis (strain 168)
Escherichia coli (strain ATCC 55124 / KO11FL)
Escherichia coli (strain ATCC 55124 / KO11FL)
Escherichia coli (strain ATCC 55124 / KO11FL)
Escherichia coli (strain ATCC 55124 / KO11FL)
Escherichia coli (strain ATCC 55124 / KO11FL)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)