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
2.1.3.2
-
RECOMMENDED NAME
GeneOntology No.
aspartate carbamoyltransferase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
carbamoyl phosphate + L-aspartate = phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
enzyme exhibits homotropic cooperativity for aspartate, is heterotropically activated by ATP and is heterotropically inhibited by CTP and UTP; reaction mechanism
-
carbamoyl phosphate + L-aspartate = phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
reaction proceeds via a nucleophilic attack by the free amino group of L-aspartate on the carbon of carbamoylphosphate
-
carbamoyl phosphate + L-aspartate = phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
reaction mechanism
-
carbamoyl phosphate + L-aspartate = phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
reaction mechanism
-
carbamoyl phosphate + L-aspartate = phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
reaction mechanism
-
carbamoyl phosphate + L-aspartate = phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
kinetic data suggest an ordered bi bi mechanism; reaction mechanism
-
carbamoyl phosphate + L-aspartate = phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
enzyme exhibits homotropic cooperativity for aspartate, is heterotropically activated by ATP and is heterotropically inhibited by CTP and UTP
-
carbamoyl phosphate + L-aspartate = phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
significant role of protein-solvent interactions in regulatory conformational changes
-
carbamoyl phosphate + L-aspartate = phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
cooperative mechanism of substrate binding
-
carbamoyl phosphate + L-aspartate = phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
allosteric enzyme, in absence of effectors, two-state, concerted transition model
-
carbamoyl phosphate + L-aspartate = phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
ordered substrate binding with induced fit
-
carbamoyl phosphate + L-aspartate = phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
catalytic and regulatory mechanisms, overview. The enzyme undergoes as it shifts between its low-activity, low-affinity form, T state, to its high-activity, high-affinity form, R state, and allosteric effectors modulate the activity. The ATCase-catalyzed reaction is regulated by nucleotide binding some 60 A from the active site, inducing structural alterations that modulate catalytic activity. The catalytic mechanism is ordered, carbamoyl phosphate binds before aspartate, and carbamoyl aspartate leaves before phosphate. Cooperativity is induced by aspartate binding
-
carbamoyl phosphate + L-aspartate = phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
ATCase follows an ordered Bi Bi reaction mechanism in which carbamoyl phosphate must bind before L-aspartate and the product N-carbamoyl-L-aspartate leaves the active site before inorganic phosphate
-
carbamoyl phosphate + L-aspartate = phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
the catalytic cycle of ATCase leads from the ordered binding of the substrates to the formation and decomposition of the tetrahedral intermediate and to the ordered release of the products from the active site, ordered-binding mechanism, detailed overview
-, P05654
carbamoyl phosphate + L-aspartate = phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
carbamoyl group transfer
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
UMP biosynthesis
-
Pyrimidine metabolism
-
Alanine, aspartate and glutamate metabolism
-
Metabolic pathways
-
SYSTEMATIC NAME
IUBMB Comments
carbamoyl-phosphate:L-aspartate carbamoyltransferase
-
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
(S)-2-methyl-3-oxopropanoyl-CoA:pyruvate carboxyltransferase
-
-
-
-
aspartate carbamyltransferase
-
-
-
-
aspartate transcarbamoylase
-
-
-
-
aspartate transcarbamoylase
O66726
-
aspartate transcarbamoylase
-
-
aspartate transcarbamoylase
P05654
-
aspartate transcarbamoylase
P0A786
-
aspartate transcarbamoylase
-
-
aspartate transcarbamoylase
Q58801
-
aspartate transcarbamoylase
Q58976
-
aspartate transcarbamoylase
Q58976
-
-
aspartate transcarbamoylase
-
-
aspartate transcarbamylase
-
-
-
-
aspartate transcarbamylase
-
-
aspartate transcarbamylase
-
-
aspartic acid transcarbamoylase
-
-
-
-
aspartic carbamyltransferase
-
-
-
-
aspartic transcarbamylase
-
-
-
-
ATC domain of CAD
-
-
-
-
ATCase
-
-
-
-
ATCase
P05654
-
ATCase
P0A786
-
ATCase
-
-
ATCase
P77918
-
ATCase
Pyrococcus furiosus GE5
-
-
-
carbamoylaspartotranskinase
-
-
-
-
carbamoyltransferase, aspartate
-
-
-
-
carbamylaspartotranskinase
-
-
-
-
L-aspartate transcarbamoylase
-
-
-
-
L-aspartate transcarbamylase
-
-
-
-
MJ1581
Q58976
locus name
CAS REGISTRY NUMBER
COMMENTARY
9012-49-1
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
; in noncovalent association with dihydroorotase, possible model for the mammalian polypeptide chain CPSase/ATCase/DHOase during pyrimidine biosynthesis
UniProt
Manually annotated by BRENDA team
expression in Escherichia coli
-
-
Manually annotated by BRENDA team
overexpression of enzyme
-
-
Manually annotated by BRENDA team
catalytic subunit trimer
Uniprot
Manually annotated by BRENDA team
regulatory subunit
Q58801
UniProt
Manually annotated by BRENDA team
Swiss albino
-
-
Manually annotated by BRENDA team
mussel
-
-
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
recombinant protein
-
-
Manually annotated by BRENDA team
Pyrococcus furiosus GE5
-
-
-
Manually annotated by BRENDA team
catalytic subunit PyrB
SwissProt
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 ACCESSION NO.
COMMENTARY
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
-, P05654
analysis of the conformational changes shows that there is a lack of cooperativity in trimeric ATCases that do not possess regulatory subunits
metabolism
-
the aspartate amino-N can be the source of nitrogen for glutamine synthesis by a substrate-channelled pathway which delivers glutamine to carbamoyl phosphate synthetase
metabolism
-
the binding of carbamoyl phosphate to the enzymes aspartate and ornithine transcarbamoylase reduces the rate of thermal decomposition of carbamoyl phosphate by a factor of >5000. Both of these transcarbamoylases use an ordered-binding mechanism in which carbamoyl phosphate binds first, allowing the formation of an enzyme-carbamoyl phosphate complex. The critical step in the thermal decomposition of carbamoyl phosphate in aqueous solution, in the absence of enzyme, involves the breaking of the C-O bond facilitated by intramolecular proton transfer from the amine to the phosphate. The binding of carbamoyl phosphate to the active sites of the enzymes significantly inhibits this process by restricting the accessible conformations of the bound ligand to those disfavoring the reactive geometry
metabolism
-
ATCase regulates the pyrimidine nucleotide biosynthesis by feedback control and by the cooperative binding of the substrate L-aspartate
metabolism
-
aspartate transcarbamoylase allosterically regulates pyrimidine nucleotide biosynthesis
metabolism
-
ATCase is an allosteric enzyme that catalyzes the committed step of pyrimidine nucleotide biosynthesis
metabolism
-, P05654
ATCase catalyzes one of the first reactions in pyrimidine nucleotide biosynthesis
physiological function
-
ATCase catalyzes the committed step, the condensation of carbamoyl phosphate and aspartate to form carbamoyl aspartate and inorganic phosphate and regulates the pyrimidine nucleotide biosynthesis by feedback control and by the cooperative binding of the substrate L-aspartate, catalytic and regulatory mechanisms, overview. Each regulatory chain is also composed of two folding domains: the Zn domain, primarily involved in the binding of the zinc cofactor, and and the Al domain, primarily involved in the binding of allosteric effectors
physiological function
-
the enzyme controls the rate of pyrimidine nucleotide biosynthesis by feedback inhibition, and helps to balance the pyrimidine and purine pools by competitive allosteric activation by ATP
physiological function
-
mechanisms of allosteric regulation in aspartate transcarbamoylase, overview
physiological function
-
aspartate transcarbamoylase allosterically regulates pyrimidine nucleotide biosynthesis
physiological function
-
allosteric transition of ATCase, R-state stabilization by disulfide linkages, overview. Wild-type ATCase displays homotropic cooperativity with respect to the second substrate Asp due a shift from the low-activity, low-affinity T state to the high-activity, high-affinity R state
physiological function
-
physically interacting with each other, carbamate kinase and ornithine carbamoyltransferase prevent thermodenaturation of carbamoyl phosphate (a precursor of pyrimidines and arginine, which is an extremely labile and potentially toxic intermediate) in the aqueous cytoplasmic environment. The carbamoyl phosphate channelling complex involves carbamate kinase, ornithine carbamoyltransferase and aspartate carbamoyltransferase
physiological function
-
the enzyme catalyzes the first step in the pyrimidine biosynthetic pathway
physiological function
-
the enzyme catalyzes the first step in the pyrimidine biosynthetic pathway
-
physiological function
Pyrococcus furiosus GE5
-
physically interacting with each other, carbamate kinase and ornithine carbamoyltransferase prevent thermodenaturation of carbamoyl phosphate (a precursor of pyrimidines and arginine, which is an extremely labile and potentially toxic intermediate) in the aqueous cytoplasmic environment. The carbamoyl phosphate channelling complex involves carbamate kinase, ornithine carbamoyltransferase and aspartate carbamoyltransferase
-
metabolism
Deinococcus radiophilus NCIMB 10648
-
the aspartate amino-N can be the source of nitrogen for glutamine synthesis by a substrate-channelled pathway which delivers glutamine to carbamoyl phosphate synthetase
-
additional information
-
importance of intradomain and intrachain interactions for the different comformational states, T and R states, active site and allosteric site structure, overview. Important for the stability of the T state are the Glu239c1 interaction with both Lys164c4 and Tyr165c4, the Asp236c1 interaction with Lys143r4, and the Ser238c1 interaction with Asn111r4. In the R state, Glu239c1 forms new interchain interactions with Lys164c1 and Tyr165c1, while Asn111r4 forms a new interaction with Glu109c4
additional information
-
allosteric and kinetic structures, overview
additional information
-
allosteric transition between the T and R enzyme states
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
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
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
P0A786
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
Pigeon
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
Q55338, -
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-, Q58976
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
Pseudomonas vulgaris
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
P77918
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
Q55338, -
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
specific for L-aspartate
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
the enzyme catalyzes the first committed step in pyrimidine biosynthesis, substrate binding causes significant conformational changes
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
Arg229, which interacts with the beta-carboxylate of L-Asp, plays a critical role in the orientation of L-Asp in the active site and demonstrates the requirement of the beta-carboxylate of L-Asp in the mechanism of domain closure and the allosteric transition in Escherichia coli ATCase
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
upon substrate binding, allosteric Escherichia coli aspartate transcarbamoylase adopts alternate quaternary structures, stabilized by a set of interdomain and intersubunit interactions, which are readily differentiated by their solution x-ray scattering curves. The cooperative binding of aspartate in aspartate transcarbamoylase appears to result from the combination of the preexisting quaternary structure equilibrium with local changes induced by binding of carbamoyl phosphate
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
there is no preferential partitioning of carbamoyl phosphate between the arginine and pyrimidine biosynthetic pathways. Channeling must occur during the dynamic association of coupled enzymes pairs. The interaction of carbamoyl-phosphate synthetase/aspartate transcarbamoylase is demonstrated by the unexpectedly weak inhibition of the coupled reaction by the bisubstrate analog, N-(phosphonacetyl)-L-aspartate. In the coupled reaction, the effective concentration of carbamoyl phosphate in the vicinity of the aspartate transcarbamoylase active site is 96fold higher than the concentration in the bulk phase. Channeling probably plays an essential role in protecting this very unstable intermediate of metabolic pathways performing at extreme temperatures
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
the enzyme catalyzes the first step in the pyrimidine biosynthetic pathway
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
Q58976
-, the enzyme catalyzes the first step in the pyrimidine biosynthetic pathway
-
-
?
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
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
P0A786
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
Pigeon
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
Q55338, -
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-, Q58976
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
Pseudomonas vulgaris
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
P77918
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
catalyzes the formation of carbamoyl-L-aspartate, the first compound unique to the biosynthetic pathway for pyrimidine nucleotides
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
catalyzes the formation of carbamoyl-L-aspartate, the first compound unique to the biosynthetic pathway for pyrimidine nucleotides
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
second enzyme of pyrimidine synthesis
-
?
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
-
-
-
-
?
L-aspartate + carbamoyl phosphate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
Q58801, Q58976
-
-
-
?
L-aspartate + carbamoyl phosphate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-, P05654
-
-
-
?
L-aspartate + carbamoyl phosphate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
i.e. ureidosuccinic acid
-
?
L-aspartate + carbamoyl phosphate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
ATCase displays ordered substrate binding and product release, remaining in the R state until substrates are exhausted. Wild-type ATCase is in a T-state structure with bound product phosphate
-
-
?
L-aspartate + carbamoyl phosphate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-, P05654
carbamoyl phosphate binding structure, in silico docking and electrostatic calculations, overview
-
-
?
additional information
?
-
-
link between enzyme activity and gametogenesis
-
-
-
additional information
?
-
-
the allosteric enzyme shows homotropic cooperative interactions between the catalytic sites for the binding of aspartate due to a quarternary structure transition between high aspartate affinity T state and R state
-
-
-
additional information
?
-
-
ACT-DHOD gene is transcribed to ACT-DHOD mRNA, translated to the single protein, ACT-DHOD, and finally converted to mature independent DHOD and ACT
-
-
-
additional information
?
-
-
concerted transition between structural and functional states of either low affinity, low activity or high affinity, high activity for aspartate. Addition of ATP along with the substrates increases the rate of the transition from the T to the R state and also decreases the duration of the R-state steady-state phase. Addition of CTP or the combination of CTP/UTP to the substrates significantly decreases the rate of the T-R transition and causes a shift in the enzyme population towards the T state even at saturating substrate concentrations
-
-
-
additional information
?
-
-
direct intermolecular interactions between the enzymes catalyzing the first three reaction steps of the de novo pyrimidine biosynthetic pathway, carbamoylphosphate synthetase II (CPSII), aspartate transcarbamoylase (ATC), and dihydroorotase (DHO), of the parasitic protist Trypanosoma cruzi, interaction analysis, overview
-
-
-
additional information
?
-
-
conformational changes due to nucleotide binding, overview
-
-
-
additional information
?
-
-
in the structure of the enzyme trapped in the R state with specific disulfide bonds, two phosphate molecules are bound per active site. The position of the first phosphate corresponds to the position of the phosphate of carbamoyl phosphate and the position of the phosphonate of inhibitor N-phosphonacetyl-L-aspartate. However, the second, more weakly bound phosphate is bound in a positively charged pocket that is more accessible to the surface than the other phosphate. The second phosphate appears to be on the path that phosphate would have to take to exit the active site
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
the enzyme catalyzes the first committed step in pyrimidine biosynthesis
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
there is no preferential partitioning of carbamoyl phosphate between the arginine and pyrimidine biosynthetic pathways. Channeling must occur during the dynamic association of coupled enzymes pairs. The interaction of carbamoyl-phosphate synthetase/aspartate transcarbamoylase is demonstrated by the unexpectedly weak inhibition of the coupled reaction by the bisubstrate analog, N-(phosphonacetyl)-L-aspartate. In the coupled reaction, the effective concentration of carbamoyl phosphate in the vicinity of the aspartate transcarbamoylase active site is 96fold higher than the concentration in the bulk phase. Channeling probably plays an essential role in protecting this very unstable intermediate of metabolic pathways performing at extreme temperatures
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
the enzyme catalyzes the first step in the pyrimidine biosynthetic pathway
-
-
?
carbamoyl phosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
Q58976
the enzyme catalyzes the first step in the pyrimidine biosynthetic pathway
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
P0A786
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
Pigeon
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
Q55338, -
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-, Q58976
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
Pseudomonas vulgaris
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
P77918
-
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
catalyzes the formation of carbamoyl-L-aspartate, the first compound unique to the biosynthetic pathway for pyrimidine nucleotides
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
catalyzes the formation of carbamoyl-L-aspartate, the first compound unique to the biosynthetic pathway for pyrimidine nucleotides
-
?
carbamoylphosphate + L-aspartate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
second enzyme of pyrimidine synthesis
-
?
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
-
-
-
-
?
L-aspartate + carbamoyl phosphate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
Q58801, Q58976
-
-
-
?
L-aspartate + carbamoyl phosphate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-, P05654
-
-
-
?
L-aspartate + carbamoyl phosphate
phosphate + N-carbamoyl-L-aspartate
show the reaction diagram
-
-
i.e. ureidosuccinic acid
-
?
additional information
?
-
-
link between enzyme activity and gametogenesis
-
-
-
additional information
?
-
-
ACT-DHOD gene is transcribed to ACT-DHOD mRNA, translated to the single protein, ACT-DHOD, and finally converted to mature independent DHOD and ACT
-
-
-
additional information
?
-
-
direct intermolecular interactions between the enzymes catalyzing the first three reaction steps of the de novo pyrimidine biosynthetic pathway, carbamoylphosphate synthetase II (CPSII), aspartate transcarbamoylase (ATC), and dihydroorotase (DHO), of the parasitic protist Trypanosoma cruzi, interaction analysis, overview
-
-
-
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
ATP
-
no effect
dATP
-
stimulates
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Zn2+
-
regulatory subunit contains 6 Zn2+ per 300000 Da protein, Zn2+ may be replaced by Hg2+ or Cd2+
Zn2+
-
the Zn domain, primarily involved in the binding of the zinc cofactor, of the regulatory chain is classified as rubredoxin-like with a metal (zinc or iron) bound that contains usually two CX(n)C motifs
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 ACCESSION NO.
COMMENTARY
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
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
acetyl phosphate
-
3 mM, 50% inhibition
ADP
-
5 mM, 19% residual activity
ADP
-
5 mM, 8% residual activity
aspartate
-
at high concentrations
ATP
-
1 mM, 40% inhibition
ATP
Q55338
inhibitory effect on the catalytic subunits encoded by the sole pyrB gene. The complete ATCase purified from recombinant Escherichia coli is strongly activated
ATP
-
excess MgCl2 abolishes inhibition
ATP
-
5 mM, 8% residual activity
ATP
-
dual regulatory pattern, activating the enzyme at low concentrations and inhibiting it in the mM range
carbamoyl aspartate
-
noncompetitive vs. carbamoyl phosphate and aspartate
carbamoyl aspartate
-
-
carbamoyl aspartate
-
-
Carbamoylaspartate
-
-
Carbonyldiphosphonate
-
-
CDP
-
10 mM, 61% inhibition
CDP
-
5 mM, 23% residual activity
CTP
-
800-1000 mM urea lower or eliminate CTP inhibition
CTP
-
competitive vs. carbamoyl phosphate
CTP
-
synergistic inhibition by CTP and UTP
CTP
-
10 mM, 79% inhibition
CTP
Q55338
inhibitory effect on the catalytic subunits encoded by the sole pyrB gene. The complete ATCase purified from recombinant Escherichia coli is strongly activated
CTP
-
allosteric inhibitor
CTP
-
5 mM, 4% residual activity
CTP
-
5 mM, 37% residual activity
CTP
-
CTP inhibits ATCase activity. Experimentally driven, statistical modeling approach (high-dimensional model representation, RS-HDMR) to investigate regulation of ATCase in response to varying concentrations of its nucleotide regulators ATP, CTP, GTP, and UTP (at fixed substrate concentrations)
CTP
-
addition of CTP or the combination of CTP/UTP to the substrates significantly decreases the rate of the low activity-high activity T-R transition and causes a shift in the enzymepopulation towards the T state even at saturating substrate concentrations
CTP
-
ATCase is feedback inhibited by CTP and synergistically by the combination of CTP plus UTP
CTP
-
aspartate transcarbamoylase is feedback inhibited by CTP in the presence of CTP. CTP and UTP do not bind competitively, CTP binding structure, overview
CTP
-
demetaled CTP, synergistic inhibition with UTP, while UTP alone has little or no influence on the enzyme activity, mechanism, overview. Binding of UTP can enhance the binding of CTP and presence of a metal ion such as Mg2+ is required for synergistic inhibition. Structure of the ATCase-CTP-UTP-Mg2+ complex
Cu2+
-
strong inhibition
dichlormethylenediphosphonate
-
-
diphosphate
-
5 mM, 6% residual activity
diphosphate
-
5 mM, 10% residual activity
Diphosphate analogues
-
-
-
GDP
-
5 mM, 39% residual activity
GDP
-
5 mM, 38% residual activity
GTP
-
1 mM, 20% inhibition
GTP
Q55338
inhibitory effect on the catalytic subunits encoded by the sole pyrB gene. The complete ATCase purified from recombinant Escherichia coli is strongly activated
GTP
-
5 mM, 11% residual activity
GTP
-
GTP inhibits ATCase activity. Experimentally driven, statistical modeling approach (high-dimensional model representation, RS-HDMR) to investigate regulation of ATCase in response to varying concentrations of its nucleotide regulators ATP, CTP, GTP, and UTP (at fixed substrate concentrations)
Guanidine-HCl
-
800 mM, almost complete inhibition
HgCl2
-
0.001 mM, 50% inhibition
hypophosphate
-
-
imidodiphosphonate
-
-
ITP
-
weak inhibition
L-aspartate
-
-
Maleate
-
15 mM, 50% inhibition
Mersalyl
-
0.01 mM, 50% inhibition
mesotartrate
-
-
Methylenediphosphonate
-
-
N-(2-hydroxy-acetyl)-L-aspartic acid-phosphate
-
competitive
N-(phosphonacetyl)-L-aspartate
-
-
N-(phosphonacetyl)-L-aspartate
-
treatment of seedling with 1 mM, results in delayed germination, inhibition of cotyledon expansion, leaf development and root growth. 2fold increase in enzyme activity and protein level
N-(phosphonacetyl)-L-aspartate
-
-
N-(phosphonacetyl)-L-aspartate
-
there is no preferential partitioning of carbamoyl phosphate between the arginine and pyrimidine biosynthetic pathways. Channeling must occur during the dynamic association of coupled enzymes pairs. The interaction of carbamoyl-phosphate synthetase/aspartate transcarbamoylase is demonstrated by the unexpectedly weak inhibition of the coupled reaction by the bisubstrate analog, N-(phosphonacetyl)-L-aspartate
N-(Phosphonoacetyl)-L-aspartate
-
-
N-(Phosphonoacetyl)-L-aspartate
-
-
N-(Phosphonoacetyl)-L-aspartate
-
-
N-(Phosphonoacetyl)-L-aspartate
-
competitive vs. carbamoyl phosphate, noncompetitive vs. aspartate
N-(Phosphonoacetyl)-L-aspartate
-
-
N-(Phosphonoacetyl)-L-aspartate
-
0.011 mM, 50% inhibition, low concentrations activate
N-(Phosphonoacetyl)-L-aspartate
-
0.0001 mM, 50% inhibition
N-(Phosphonoacetyl)-L-aspartate
-
0.002 mM, 50% inhibition of catalytic subunit
N-(phosphonoacetyl)-L-aspartic acid
-
-
N-Diphosphoryl-L-aspartate
-
-
N-methyl phosphonoacetamide
-
-
N-phosphonacetyl-L-asparagine
-
potent inhibitor of ATCase
N-phosphonacetyl-L-aspartate
-
PALA, a bisubstrate transition state analogue, and shows also ability of PALA to enhance the activity of ATCase at low concentrations of aspartate, in the presence of a saturating concentration of carbamoyl phosphat. Interactions between the side chain of Gln137 and the backbone carbonyl oxygen of Pro266 to the amino group on the tetrahedral carbon and the side chain of Arg54 with the ester oxygen between the phosphorus and the tetrahedral carbone
N-phosphonacetyl-L-aspartate
-
i.e. PALA, a bisubstrate analogue, the binding of PALA is able to stabilize the enzyme in the high-activity, high-affinity R state because its structure mimics the reaction's transition state structure. The concerted transition to the R state allows a majority of active sites free to react with substrates and release products while a minority of active sites bound with PALA are inactive but stabilize the enzyme in the R state. Therefore, at low concentrations of PALA the activity increases; however, as the concentration of PALA is increased more and more of the active sites are filled by the non-hydrolyzable bisubstrate analog and the activity drops. At high concentrations of Asp and a saturating concentration of carbamoyl phosphate, no PALA activation is observed. In the absence of allosteric effectors the average KD of PALA is 110 nM, decreasing to 65 nM in the presence of ATP and increasing to 266 nM in the presence of CTP
N-phosphonacetyl-L-aspartate
-
-
N-phosphonacetyl-L-aspartate
-, P05654
a bisubstrate/transition state analogue, binding structure, in silico docking and electrostatic calculations, overview
N-phosphonoacetyl-L-aspartate
-
competitive
N-phosphonoacetyl-L-aspartate
-
after addition of N-phosphonacetyl-L-aspartate to the enzyme, the transition rate is more than 1 order of magnitude slower than with the natural substrates
N-phosphoryl-L-aspartate
-
-
N-pyrophosphoryl-L-aspartate
-
-
O-phosphonoacetyl-oxosuccinate
-
-
p-chloromercuribenzoate
-
-
p-chloromercuribenzoate
-
6 mM, almost complete inhibition
p-hydroxymercuribenzoate
-
strong inhibition
p-hydroxymercuribenzoate
-
-
p-mercuribenzoate
-
0.01 mM, 50% inhibition
Phenylglyoxal
-
-
phosphate
-
competitive vs. carbamoyl phosphate, noncompetitive vs. aspartate
phosphonoacetamide
-
-
Phosphonoacetate
-
-
phosphonoacetic acid arsenate
-
-
-
phosphonoacetic acid arsenate
-
1 mM, 50% inhibition
-
Phosphonoformate
-
-
phosphonopropionate
-
-
S-diphosphoryl-mercaptosuccinate
-
-
S-phosphonoacetyl-mercaptosuccinate
-
-
succinate
-
activator at low concentrations of both succinate and aspartate, inhibitor at high succinate concentrations and at high aspartate concentrations
succinate
-
10 mM, 50% inhibition
succinate
-
-
UDP
-
1 mM, 45% inhibition
UDP
-
5 mM, 11% residual activity
UDP
-
5 mM, 7% residual activity
UMP
-
0.1 mM, 25% inhibition, inhibition increases to 80% and 90% in the presence of 0.2 mM and 0.6 mM deoxycholate respectively
UMP
-
0.8 mM, 85% inhibition
UMP
-
1 mM, 75% inhibition
UMP
-
fatty acids with chains of C8 or longer, dodecylsulfate and decylsulfonate potentiate inhibition
UMP
-
5 mM, 6% residual activity
UMP
-
5 mM, 21% residual activity
Urea
-
2.5 M, almost complete inhibition
UTP
-
weak inhibition
UTP
-
synergistic inhibition by CTP and UTP, no inhibition unless CTP is present
UTP
-
1 mM, 40% inhibition
UTP
Q55338
inhibitory effect on the catalytic subunits encoded by the sole pyrB gene. The complete ATCase purified from recombinant Escherichia coli is strongly activated
UTP
-
allosteric inhibitor
UTP
-
UTP inhibits ATCase activity. Experimentally driven, statistical modeling approach (high-dimensional model representation, RS-HDMR) to investigate regulation of ATCase in response to varying concentrations of its nucleotide regulators ATP, CTP, GTP, and UTP (at fixed substrate concentrations)
UTP
-
addition of CTP or the combination of CTP/UTP to the substrates significantly decreases the rate of the low activity-high activity T-R transition and causes a shift in the enzymepopulation towards the T state even at saturating substrate concentrations
UTP
-
aspartate transcarbamoylase is feedback inhibited by UTP in the presence of CTP. UTP binds to a unique site on each regulatory chain of the enzyme that is near but not overlapping with the known CTP site. CTP and UTP do not bind competitively, UTP binds to the r6 regulatory chain of ATCase, UTP binding structure, overview
UTP
-
inhibition with CTP, while UTP alone has little or no influence on the enzyme activity, mechanism, overview. UTP, in the presence of dCTP or CTP, binds at a site on a regulatory side chain that does not overlap the CTP/dCTP site, and the triphosphates of the two nucleotides are parallel to each other with a metal ion, in this case Mg2+, coordinated between the beta- and gamma-phosphates of the two nucleotides. UTP binds more tightly in the presence of CTP. Structure of the ATCase-CTP-UTP-Mg2+ complex
additional information
-
not inhibited by CTP
-
additional information
-
50% inhibition at 80 MPa; not inhibited by phosphonoacetate, diphosphate or phosphate
-
additional information
-
kinetic analysis of properties of allosteric effectors alone and in combination with each other
-
additional information
-
conformational changes due to nucleotide binding, overview
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
4-aminobutyrate
-
400% activation
4-aminobutyrate
-
-
acetate
-
25 mM, 2.3fold activation
adenosine
-
very weak activation
Aminoethanol
-
activates
ATP
Q55338
holoenzyme, catalytic subunits alone are inhibited
ATP
-
allosteric activator, up to 35% increase in Vmax
ATP
-
allosteric effector, increases the apparent rate of unliganded T-state to substrate-bound R-state
ATP
-
ATP enhances ATCase activity. Experimentally driven, statistical modeling approach (high-dimensional model representation, RS-HDMR) to investigate regulation of ATCase in response to varying concentrations of its nucleotide regulators ATP, CTP, GTP, and UTP (at fixed substrate concentrations)
ATP
-
dual regulatory pattern, activating the enzyme at low concentrations and inhibiting it in the mM range
ATP
-
addition of ATP along with the substrates increases the rate of the transition from the low activity T to the high activity R state and also decreases the duration of the R-state steady-state phase
ATP
-
the effects of binding of nucleotides are monitored in a series of 1H-13C methyl TROSY spectroscopy spectra recorded on the 300 kDa aspartate transcarbamoylase holoenzyme in both the absence and the presence of saturating amounts of ATP or CTP. No changes in shifts of methyl probes of the catalytic chains that include the active sites are observed, consistent with a lack of structural changes. Results indicate that the mechanism of action of ATP and CTP can be explained fully by the Monod-Wyman-Changeux model
beta-Alanine
-
600% activation
Butyrate
-
5700% activation
Carbamoyl-beta-alanine
-
5000% activation
Carbamoyl-beta-alanine
-
-
CTP
Q55338
holoenzyme, catalytic subunits alone are inhibited
CTP
-
allosteric effector, slightly shifts the dynamical equilibrium during steady state toward unliganded T-state
CTP
-
the effects of binding of nucleotides are monitored in a series of 1H-13C methyl TROSY spectroscopy spectra recorded on the 300 kDa aspartate transcarbamoylase holoenzyme in both the absence and the presence of saturating amounts of ATP or CTP. No changes in shifts of methyl probes of the catalytic chains that include the active sites are observed, consistent with a lack of structural changes. Results indicate that the mechanism of action of ATP and CTP can be explained fully by the Monod-Wyman-Changeux model
D-Aspartate
-
5700% activation
dimethyl sulfoxide
-
strong stimulation
Dimethylformamid
-
strong stimulation
Dimethylformamide
-
-
dimethylsulfamide
-
-
formate
-
activates
GTP
Q55338
holoenzyme, catalytic subunits alone are inhibited
Hydroxylamine-HCl
-
30 mM, 2120% activation
Imidazole-HCl
-
30 mM, 2710% activation
Isobutyrate
-
5800% activation
L-2-aminobutyrate
-
1400% activation
L-2-aminobutyrate
-
-
L-alanine
-
800% activation
L-Malate
-
activation in presence of excess carbamoyl phosphate and limiting L-aspartate
N-(Phosphonoacetyl)-L-aspartate
-
at concentrations below 0.001 mM
N-(Phosphonoacetyl)-L-aspartate
-
at concentrations below 0.000002 mM, inhibition above
N-phosphonacetyl-L-aspartate
-
PALA, a bisubstrate transition state analogue, and shows also ability of PALA to enhance the activity of ATCase at low concentrations of aspartate, in the presence of a saturating concentration of carbamoyl phosphate. Interactions between the side chain of Gln137 and the backbone carbonyl oxygen of Pro266 to the amino group on the tetrahedral carbon and the side chain of Arg54 with the ester oxygen between the phosphorus and the tetrahedral carbon
N-phosphonacetyl-L-aspartate
-
i.e. PALA, a bisubstrate analogue, the binding of PALA is able to stabilize the enzyme in the high-activity, high-affinity R state because its structure mimics the reaction's transition state structure. The concerted transition to the R state allows a majority of active sites free to react with substrates and release products while a minority of active sites bound with PALA are inactive but stabilize the enzyme in the R state. Therefore, at low concentrations of PALA the activity increases; however, as the concentration of PALA is increased more and more of the active sites are filled by the non-hydrolyzable bisubstrate analog and the activity drops. At high concentrations of Asp and a saturating concentration of carbamoyl phosphate, no PALA activation is observed
NaCl
-
30 mM, 1730% activation
NH4Cl
-
30 mM, 2710% activation
Propionate
-
5600% activation
succinate
-
activation in presence of excess carbamoyl phosphate and limiting L-aspartate
succinate
-
low concentrations, 35% activation in the presence of 2 mM aspartate
Triethanolamine-HCl
-
30 mM, 1950% activation
Tris-HCl
-
30 mM, 2620% activation
UTP
Q55338
holoenzyme, catalytic subunits alone are inhibited
UTP
-
allosteric effector, makes steady state vanishingly short
mesotartrate
-
activation in presence of excess carbamoyl phosphate and limiting L-aspartate
additional information
-
not activated by ATP
-
additional information
-
every type of anion tested, including ATP and CTP can stimulate the reaction to a certain extent
-
additional information
-
at high aspartate levels addition of an activator has no effect
-
additional information
-
activity is not regulated by nucleotide triphosphates
-
additional information
-
kinetic analysis of properties of allosteric effectors alone and in combination with each other
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
7
-
aspartate
-
-
0.004
-
Carbamoyl phosphate
-
in crude extracts of fibroblasts
0.005
-
Carbamoyl phosphate
-
37C
0.0077
-
Carbamoyl phosphate
-
-
0.014
-
Carbamoyl phosphate
-
-
0.02
-
Carbamoyl phosphate
-
multienzyme complex and aspartate transcarbamoylase activity domain of the multienzyme complex alone
0.0207
-
Carbamoyl phosphate
-
-
0.023
-
Carbamoyl phosphate
-
in the absence of UMP
0.028
-
Carbamoyl phosphate
-
-
0.038
-
Carbamoyl phosphate
-
recombinant catalytic subunit, at 37C
0.091
-
Carbamoyl phosphate
-
-
0.11
-
Carbamoyl phosphate
-
-
0.2
-
Carbamoyl phosphate
-
at high salt concentrations
0.2
-
Carbamoyl phosphate
Q55338
holoenzyme
0.3
-
Carbamoyl phosphate
-
-
0.34
-
Carbamoyl phosphate
-
30C
0.49
-
Carbamoyl phosphate
-
-
0.55
-
Carbamoyl phosphate
-
pH 8.0, 37C
0.6
-
Carbamoyl phosphate
Q55338
catalytic subunits
0.61
-
Carbamoyl phosphate
-
in cell extracts
1.26
-
Carbamoyl phosphate
-
pH 8.0, 75C
3.2
-
Carbamoyl phosphate
-
pH 8.23, 37C
3.93
-
Carbamoyl phosphate
-
pH 9.4, 37C
7
-
Carbamoyl phosphate
-
-
88
-
Carbamoyl phosphate
-
at 25C
162
-
Carbamoylphosphate
-
at 37C
122
-
L-asparagine
-
-
0.009
-
L-aspartate
-
multienzyme complex
0.021
-
L-aspartate
-
aspartate transcarbamoylase activity domain of the multienzyme complex alone
0.02134
-
L-aspartate
-
-
0.16
-
L-aspartate
-
-
1
-
L-aspartate
-
pH 8.0, 37C
1.12
-
L-aspartate
-
pH 8.0, 75C
2.3
-
L-aspartate
-
C47A/A241C mutant enzyme
2.6
-
L-aspartate
-
-
2.75
-
L-aspartate
-
-
2.96
-
L-aspartate
-
30C
4
-
L-aspartate
-
mutant K244N, pH 8.3, 25C
6.25
-
L-aspartate
-
pH 8.23, 37C
7
-
L-aspartate
-
-
7.35
-
L-aspartate
-
pH 9.4, 37C
7.9
-
L-aspartate
-
complex of catalytic and regulatory subunits, C3R6
8.4
-
L-aspartate
-
mutant K244A, pH 8.3, 25C
10
-
L-aspartate
-
-
10.9
-
L-aspartate
-
at 55C
11.6
-
L-aspartate
-
in cell extracts
12
-
L-aspartate
-
-
12.3
-
L-aspartate
-
recombinant catalytic subunit, at 30C
12.4
-
L-aspartate
-
wild-type, pH 8.3, 25C
14.1
-
L-aspartate
-
recombinant catalytic subunit, at 45C
15.5
-
L-aspartate
-
recombinant catalytic subunit, at 37C
18
-
L-aspartate
-
-
18.2
-
L-aspartate
-
at 37C
19.7
-
L-aspartate
-
recombinant catalytic subunit, at 55C
34.6
-
L-aspartate
-
at 25C
40.4
-
L-aspartate
-
at 15C
44.7
-
L-aspartate
-
complex of catalytic subunits, C3
additional information
-
additional information
-
sigmoidal saturation curve for carbamoylphosphate and aspartate
-
additional information
-
additional information
-
enzyme exhibits Michaelis-Menten kinetics for both of its substrates
-
additional information
-
additional information
-
-
-
additional information
-
additional information
Q55338
sigmoidal saturation curve for aspartate
-
additional information
-
additional information
-
sigmoidal saturation curve for aspartate
-
additional information
-
additional information
-
study of enzyme kinetics under high pressure, in presence of low concentration of L-aspartate, pressure promotes the transition to R-state
-
additional information
-
additional information
-
the allosteric enzyme shows homotropic cooperative interactions between the catalytic sites for the binding of aspartate, neuron scattering, protein dynamics, overview
-
additional information
-
additional information
-
the saturation curve is cooperative exhibiting a pH dependent Hill coefficient, cooperative kinetics, modeling with the enzyme being in a dynamic equilibrium between a low-activity, low-affinity T state and a high-activity, high-affinity R state
-
additional information
-
additional information
-
aspartate transcarbamoylase is an allosteric enzyme, quaternary structural changes during the allosteric transition, and kinetics of the allosteric transition, overview
-
additional information
-
additional information
-
allosteric mechanism with metal ion involvement, overview
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
79.7
-
aspartate
-
aspartate transcarbamoylase activity domain of the multienzyme complex
35.9
-
Carbamoyl phosphate
-
aspartate transcarbamoylase activity domain of the multienzyme complex
47.2
-
Carbamoyl phosphate
-
-
57.4
-
Carbamoylphosphate
-
multienzyme complex
5.6
-
L-aspartate
-
pH 8.0, 37C
41.7
-
L-aspartate
-
pH 8.0, 75C
156
-
L-aspartate
-
multienzyme complex
417
-
L-aspartate
-
-
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
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
-
when carbamoyl phosphate is limiting
7
-
carbamoyl aspartate
-
competitive vs. carbamoyl phosphate
15
-
carbamoyl aspartate
-
competitive vs. L-aspartate
13
-
Carbamoylaspartate
-
noncompetitive vs. carbamoyl phosphate
0.0035
-
Carbonyldiphosphonate
-
-
0.1
-
CDP
-
when carbamoyl phosphate is limiting
1.1
-
chloride
-
inhibition of catalytic subunits, C3
0.007
-
CTP
-
when carbamoyl phosphate is limiting
0.037
-
CTP
-
-
0.032
-
dichlormethylenediphosphonate
-
-
0.0004
-
diphosphate
-
when carbamoyl phosphate is limiting
0.0004
-
diphosphate
-
-
0.051
-
diphosphate
-
-
0.09
-
diphosphate
-
-
0.9
-
diphosphate
-
competitive vs. carbamoyl phosphate
2
-
ethylamidocarbonylphosphonate
-
-
-
5.3
-
fumarate
-
inhibition of catalytic subunits, C3
0.02
-
hypophosphate
-
-
0.071
-
imidodiphosphonate
-
-
4.59
-
L-aspartate
-
aspartate transcarbamoylase activity domain of the multienzyme complex
7.9
-
L-aspartate
-
substrate inhibition, complex of catalytic and regulatory subunits, C3R6
13.56
-
L-aspartate
-
multienzyme complex
0.17
-
Maleate
-
inhibition of catalytic subunits, C3
1
-
Maleate
-
competitive vs. L-aspartate
0.7
-
mesotartrate
-
inhibition of catalytic subunits, C3
0.00021
-
N-(2-hydroxy-acetyl)-L-aspartic acid-phosphate
-
catalytic subunit of aspartate transcarbamoylase
0.000001
-
N-(phosphonacetyl)-L-aspartate
-
-
0.000022
-
N-(phosphonacetyl)-L-aspartate
-
-
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
-
phosphate
-
when carbamoyl phosphate is limiting
5
-
phosphate
-
competitive vs. carbamoyl phosphate
14
-
phosphate
-
competitive vs. L-aspartate
0.66
-
phosphonoacetamide
-
-
0.15
-
Phosphonoacetate
-
-
0.022
-
Phosphonoformate
-
-
1.5
-
ribose-5-P
-
when carbamoyl phosphate is limiting
1.5
-
ribose-5-P
-
-
0.017
-
S-diphosphoryl-mercaptosuccinate
-
-
0.0055
-
S-phosphonoacetyl-mercaptosuccinate
-
-
3.5
-
succinate
-
inhibition of catalytic subunits, C3
0.00049
-
UMP
-
-
0.0085
-
UTP
-
when carbamoyl phosphate is limiting
0.037
-
Methylenediphosphonate
-
-
additional information
-
additional information
-
Ki-values at varying concentrations of Asp and carbamoyl phosphate
-
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.2
-
2-methylquinazolin-4(3H)-one
-
-
0.15
-
2-phenyl-1,3-4(H)benzothiazin-4-thione
-
-
0.35
-
3-amino-6,8-dibromo-2-methyl-4(3H)-quinazolinone
-
-
0.18
-
3-amino-6,8-dibromo-2-phenyl-4-(3H)-quinazolinone
-
-
0.000055
-
N-(phosphonoacetyl)-L-aspartic acid
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
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
29.95
-
Q55338
at 55C
32.8
-
-
30C, presence of 5 mM CMP
35.3
-
-
30C
116.7
-
-
-
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
-
-
specific activity of the catalytic subunit alone is about 50% higher than that of the holoenzyme
additional information
-
-
highest activity in Tris-HCl buffer, followed by Tris-acetate EDTA, glycine sodium and cacodylate buffer
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7
-
-
presence of low concentration of L-aspartate
7
-
-
assay at
7.5
-
-
assay at
8
-
-
maxima at pH 8.0 and pH 10.2
8
-
-
sharp decline in activity below and above
8.2
-
-
presence of high concentration of L-aspartate
8.5
-
-
maxima at pH 8.5 and pH 10.2
9
10
-
-
9.2
-
-
-
10.2
-
-
maxima at pH 8.5 and pH 10.2
10.2
-
-
maxima at pH 8.0 and pH 10.2
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7
8.5
-
steep increase in activity until pH 8.5, decrase above
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
25
-
-
assay at
37
-
-
assay at
37
-
-
-
37
-
-
assay at
TEMPERATURE RANGE
TEMPERATURE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
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 ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
fibroblast cell line MA-134
Manually annotated by BRENDA team
-
simian virus 40 transformed syrian hamster cell line
Manually annotated by BRENDA team
-
high acitivity at development and ripe stage, low in indifferent, spawning or spent stage
Manually annotated by BRENDA team
Pigeon
-
-
Manually annotated by BRENDA team
-
markedly increased expression of PYRB in root tissues during the first 5 days after germination
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Bacillus subtilis (strain 168)
Bacillus subtilis (strain 168)
Bacillus subtilis (strain 168)
Bacillus subtilis (strain 168)
Escherichia coli (strain ATCC 55124 / KO11)
Escherichia coli (strain ATCC 55124 / KO11)
Escherichia coli (strain ATCC 55124 / KO11)
Escherichia coli (strain ATCC 55124 / KO11)
Escherichia coli (strain ATCC 55124 / KO11)
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)
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)
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)
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)
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)
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 O139:H28 (strain E24377A / ETEC)
Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440)
Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440)
Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440)
Pyrococcus abyssi (strain GE5 / Orsay)
Sulfolobus acidocaldarius (strain ATCC 33909 / DSM 639 / JCM 8929 / NBRC 15157 / NCIMB 11770)
Sulfolobus acidocaldarius (strain ATCC 33909 / DSM 639 / JCM 8929 / NBRC 15157 / NCIMB 11770)
Trypanosoma cruzi (strain CL Brener)
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
32000
-
-
regulatory subunit, gel filtration
83000
-
-
gel filtration
93000
-
-
250000 Da and 93000 Da isoforms
93000
-
-
glycerol gradient
100000
-
Pseudomonas vulgaris
-
100000 Da and 300000 Da isofomrms
102000
-
-
sedimentation velocity and sedimentation equilibrium analysis
112800
-
-
gel filtration
120000
140000
-
-
125000
-
-
sucrose density gradient centrifugation
128000
-
-
sedimentation equilibrium
128000
-
-
gel filtration, sedimentation data
129000
-
-
catalytic subunit, gelfiltration
220000
-
-
analytical ultracentrifugation
246000
-
-
gel filtration
250000
-
-
250000 Da and 93000 Da isoforms
300000
-
-
-
301000
-
-
gel filtration
310000
-
-
sedimentation equilibrium
310000
-
-
-
320000
-
-
gel filtration
340000
-
Q55338
gel filtration; holoenzyme, gel filtration
360000
-
-
sedimentation equilibrium
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 17000 + x * 34000, SDS-PAGE
?
-
x * 37000 + x * 17000, most probably a dodecamer, SDS-PAGE
?
-
x * 35000, SDS-PAGE
dimer
-
2 * 180000, SDS-PAGE
dimer
-
1 * 138000 + 1 * 108000, SDS-PAGE
dodecamer
-
6 * 33000 + 6 * 17000, 2C3/3R2 holoenzyme
dodecamer
Q55338
6 * 36500 + 6 * 18000, SDS-PAGE
dodecamer
-
6 * 45000 + 6 * 36000, SDS-PAGE
dodecamer
-
6 * 35000 + 6 * 17000, 2C3/3R2 holoenzyme, calculated
dodecamer
-
quaternary structural changes during the allosteric transition, overview
heterooligomer
-
x * 96000 + x * 30000
hexamer
-
6 * 20600
tetramer
-
4 * 32500, SDS-PAGE
trimer
-
3 * 33500, SDS-PAGE, sedimemtation equilibrium analysis of protein dissolved in 6 M guanidine hydrochloride
trimer
-
3 * 37000, SDS-PAGE, recombinant enzyme with His-tag, 3 * 33557, calculated
trimer
-
crystallization data
trimer
-
crystals of the catalytic subunit in an orthorhombic crystal form contain four crystallographically independent trimers which associate in pairs to form stable staggered complexes. Each subunit has a sulfate in the central channel. The catalytic subunits in these complexes show flexibility, with the elbow angles of the monomers differing by up to 7.4 between crystal forms. There is also flexibility in the relative orientation of the trimers around their threefold axis in the complexes, with a difference of 4 between crystal forms
hexamer
-, O66726
noncovalent association with dihydroorotase
additional information
-
-
additional information
-
2 distinct kinds of separable subunits, a catalytically active C subunit of 33000 Da and a regulatory R subunit of 17000 Da, native structure: (C3)2(R2)3 i.e. a dimer of C subunits and a trimer of R subunits
additional information
-
-
additional information
-
model for homotrophic cooperativity
additional information
-
characterization of a complex between catalytical and regulatory subunit
additional information
-
crosslinking of subunits with tartryl diazide
additional information
-
hamster aspartate carbamoyltransferase domain is an oligomer consisting of 2 or 3 identical copies of the 40000 Da proteolytic fragment of CAD, 2 or 3 * 40000, SDS-PAGE
additional information
-
-
additional information
-
dodecameric structure, 2C3:3R2 i.e. 2 trimers of the catalytic subunit and 3 dimers of the regulatory subunit
additional information
-
holoenzyme is a dodecamer composed of 2 catalytic trimers and 3 regulatory dimers, the catalytic chain is composed of 2 structural domains, the aspartate domain and the carbamoylphosphate domain which are involved in the binding of aspartate and carbamoylphosphate respectively, the regulatory chain is also composed of 2 domains, the allosteric and the zinc domains, which are involved in the binding of allosteric effectors and zinc
additional information
-
channeling and transient complex formation between enzyme and carbamoyl phosphate synthetase
additional information
-
C1-R2 type interface between subunits
additional information
-
quarternary structure and substrate binding-mediated conformational changes analyzed by inelastic neuron scattering using bisubstrate analogue N-(phosphonacetyl)-L-aspartate binding, protein dynamics, overview
additional information
-
ATCase and dihydroorotase form a non-covalently bonded complex which probably consists of six polypeptide chains of dihydroorotase and six of ATCase. All the ATCase and dihydroorotase activity in Deinococcus radiophilus occurs in the form of this complex
additional information
-
the larger subunit retains catalytic activity while the smaller subunit exhibits no activity but it contains the nucleotide binding regulatory sites, and three-dimensional and quaternary structure of ATCase, and secondary structure of a regulatory chain and a catalytic chain of ATCase, detailed overview
additional information
Deinococcus radiophilus NCIMB 10648
-
ATCase and dihydroorotase form a non-covalently bonded complex which probably consists of six polypeptide chains of dihydroorotase and six of ATCase. All the ATCase and dihydroorotase activity in Deinococcus radiophilus occurs in the form of this complex
-
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
complex of aspartate transcarbamoylase and dihydroorotase; noncovalent hexamer of dihydroorotase and ATCase, to 2.3 A resolution. The structure has citrate, bound to the active sites of both enzymes.Six DHO and six ATC chains form a hollow dodecamer, in which the 12 active sites face an internal reaction chamber that is approximately 60 A in diameter and connected to the cytosol by narrow tunnels. The entrances and the interior of the chamber are both electropositive, which suggests that the architecture of this nanoreactor modifies the kinetics of the bisynthase, not only by steric channeling but also by preferential escape of the product, dihydroorotase
-, O66726
50 mM Tis-HCl, pH 8.1, 70% ammonium sulfate
-
purified recombinant enzyme alone or complex with substrate carbamoyl phosphate or inhibitor N-phosphonacetyl-L-aspartate, hanging drop vapor diffusion method, 12 mg/ml protein is mixed with an equal volume of crystallization buffer containing 1.7 M (NH4)2SO4, 0.1 M Tris-HCl, pH 8.5, and 2.0% PEG 200, and equilibratopn over a reservoir of 0.5 ml of crystallization buffer at 20C, 1 week, for substrate bound enzyme the crystals are soaked in mother liquor containing the ligand at 13.3 mM, for inhibitor bound form, the enzyme is crystallized as described using crystallization buffer containing 0.1 M potassium bromide, 0.1 M N-cyclohexyl-3-aminopropanesulfonic acid, pH 10.0, and 18% PEG 8000, 20C, 1 week, X-ray diffraction structure determination and analysis at 2.1-2.6 A resolution
-, P05654
approx. 30% ammonium sulfate, crystals appear after about 2 weeks at 4C
-
ATCase locked in the R quaternary structure by specific introduction of disulfide bonds bound to the final product molecule phosphate, 10 mg/ml protein solution is dialyzed against a solution of 100 mM potassium dihydrogen phosphate and 3 mM sodium azide, pH 5.9, 1 week, X-ray diffraction structure determination and analysis at 2.85 A resolution, molecular replacement
-
bound to N-phosphonacetyl-L-aspartate, citrate or phosphate, crystalline R-state P212121
-
cocrystallization of catalytic subunit with N-(phosphonoacetyl)-L-aspartate by vapor diffusion, crystals grow from 0.005 ml of 100 mM Tris-HCl, pH 6.8, 20 mM calcium acetate, 5.8% polyethylene glycol 8000 and 0.005 ml of catalytic subunit in 10 mM Tris-HCl, pH 7.5, 1 mM 2-mercaptoethanol and 2 mM N-(phosphonoacetyl)-L-aspartate
-
hanging drop vapor diffusion, X-ray structure of unliganded ATCase at pH 8.5
-
microdialysis method, structure of D236A ATCase in the presence of phosphonoactamide and Asp
-
mutant E50A, in presence of phosphonoacetamide and malonate to trap the enzyme in T-like and R-like structures
-
mutant K244N, loss of numerous local T-state stabilizing interactions
-
purified recombinant ATCase in complex with UTP, CTP, or dCTP, dialysis of 20 mg/ml protein against 40 mM sodium citrate, 1 mM 2-mercaptoethanol, 0.2 mM EDTA, and 1.0 mM CTP, pH 5.7, at 20C, 1 week, transfer of dialysis buttons to 2 mL of crystallization buffer with 5 mM UTP and 5 mM MgCl2 and equilibration for 12 h, and to crystallization buffer containing 5 mM UTP and 5 mM MgCl2 for 12 h, respectively, cryoprotection in 20% 2-methyl-2,4-pentanediol in UTP-Mg2+ crystallization buffer, X-ray diffraction structure determination and analysis at 1.9-2.1 A resolution
-
purified recombinant mutant enzyme K164E/E239K, mixing of 10 mg/ml enzyme in 50 mM Tris-acetate, pH 8.3, with 0.002 ml of crystallization buffer containing 16% w/v PEG 4000, 0.04 M Na2MoO4-2H2O, 0.04 M N-cyclohexyl-3-aminopropanesulfonic acid, and 30 mM Tris-acetate, pH 8.75, and equilibration over a reservoir of crystallization buffer of 1.0 ml, 20C, 2 weeks, X-ray diffraction structure determination and analysis
-
series of X-ray crystal structures of the enzyme in the presence and absence of substrates, products, and analogues, structure analysis, detailed overview. The structure of the enzyme in the presence of citrate, an analogue of N-carbamoyl-L-aspartate plus the product phosphatewas determined after displacement of N-phosphonacetyl-L-aspartate from R-state crystals
-
use of Methyl-TROSY spectra for assignment for approximately 60% of the observed methyl groups in TROSY maps of ATCase by the divide and conquer method. The combination of all approaches leads to assignments for 86% of the methyl groups, providing a large number of probes of structure and dynamics. The derived assignments are used to interpret chemical shift changes of ATCase upon titration with the nucleotide ATP. Large shift changes in the N-terminal tails of the regulatory chain provide the first evidence for structural perturbations in a region playing a critical role on the effect of nucleotide binding on distal catalytic sites of the allosteric enzyme
-
X-ray crystal structure of the N-phosphonacetyl-L-asparagine complexed with ATCase. Analysis of the crystal structure of the enzyme in the presence of N-phosphonacetyl-L-asparagine reveals that the binding of N-phosphonacetyl-L-asparagine is similar to that of the R-state complex of ATCase with N-phosphonaceyl-L-aspartate, another potent inhibitor of the enzyme
-
X-ray structure at 5.5 A resolution
-
X-ray structure of the holoenzyme in the presence of the substrate analog N-phosphonoacetyl-L-aspartate, carbamoylphosphate and succinate
-
X-ray structures of wild-type Escherichia coli aspartate transcarbamoylase holoenzyme and catalytic subunit crystallized with different ligands, overview
-
catalytic chain in the presence of the regulatory chain in the hexagonal space group P6322, with one monomer per asymmetric unit, sitting drop vapor diffusion method, mixing of 0.0013 protein-ligand solution, containing 11 mg/ml protein in 50 mM Tris, pH 8.3, 150 mM NaCl, 2 mM BME, 0.05 mM zinc acetate, with 0.001 ml of reservoir solution containing 2.0 M ammonium sulfate, 0.2 M potassium sodium tartrate tetrahydrate, 0.1 M sodium citrate tribasic dihydrate, pH 5.6, or 2.0 M ammonium sulfate, 0.2 M potassium sodium tartrate tetrahydrate, 0.1 M Tris-HCl, pH 7.5, 22C, X-ray diffraction structure determination and analysis at 2.50 A resolution, molecular replacement; catalytic chain in the presence of the regulatory chain in the hexagonal space group P6322, with one monomer per asymmetric unit, sitting drop vapor diffusion method, mixing of 0.0013 protein-ligand solution, containing 11 mg/ml protein in 50 mM Tris, pH 8.3, 150 mM NaCl, 2 mM BME, 0.05 mM zinc acetate, with 0.001 ml of reservoir solution containing 2.0 M ammonium sulfate, 0.2 M potassium sodium tartrate tetrahydrate, 0.1 M sodium citrate tribasic dihydrate, pH 5.6, or 2.0 M ammonium sulfate, 0.2 M potassium sodium tartrate tetrahydrate, 0.1 M Tris-HCl, pH 7.5, 22C, X-ray diffraction structure determination and analysis at 2.50 A resolution, molecular replacement
Q58801, Q58976
crystals are grown at 295 K by the sitting-drop method from reservoirs containing 2.0 M ammonium sulfate and 5% 2-propanol. The catalytic trimer is crystallized in space group R32, with unit-cell parameters a = b = 265.3, c = 195.5 A and two trimers in the asymmetric unit. Its structure is determined using molecular replacement and Patterson methods
-
crystals of the catalytic subunit in an orthorhombic crystal form contain four crystallographically independent trimers which associate in pairs to form stable staggered complexes. Each subunit has a sulfate in the central channel. The catalytic subunits in these complexes show flexibility, with the elbow angles of the monomers differing by up to 7.4 between crystal forms. There is also flexibility in the relative orientation of the trimers around their threefold axis in the complexes, with a difference of 4 between crystal forms
-
sitting drop method, crystal structure of the catalytic trimer
-
3 catalytic and 3 regulatory subunits per asymmetric unit
-
the crystal structure of the unliganded Moritella profunda ATCase shows resemblance to a more extreme T state reported previously for an Escherichia coli ATCase mutant
-
hanging drop method, equal volumes of 1 mg/ml enzyme in 100 mM Tris-HCl, pH 8.5 is mixed with 100 mM citrate, pH 5, and 10% 6K polyethylene glycol
-
hanging-drop vapour-diffusion, 0.002 ml of enzyme solution, 7 mg/ml, in 20 mM Tris-HCl, pH 8.2, 2 mM 2-mercaptoethanol, 300 mM NaCl, is mixed with 0.002 ml reservoir solution consisting of 1.4 M citrate, pH 6.8, X-ray structure to 1.8 A resolution
-
; hanging drop vapour-diffusion technique at 20C. Tertiary and quaternary structure of the T state ATCase of the enzyme determined by X-ray crystallography to 2.6 A resolution
-
aspartate carbamoyltransferase in complex with its allosteric activator CTP
-
in ligand free form and in complex with carbamoyl phosphate to 2.8 A and to 1.6 A resolution, respectively. Presence of two homotrimers in the asymmetric unit
-
pH STABILITY
pH STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6
-
-
unstable below
6.6
-
-
stable
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0
25
-
quite stable
45
-
-
loss of activity after 10 min, carbamoylphosphate protects
50
-
-
5 min, no loss of activity
55
65
-
4 min, loss of 70% of secondary structure in absence of solutes, Tm is highly enhanced in presence of KCl, NaCl, or alpha and beta isomers of K+-glutamate, NaCl, KCl, glycine, and betaine are not thermoprotective, but trehalose, sucrose, and K+-glutamate are, K+-glutamate raises Tm and maintains enzyme activity, overview
55
-
-
5 min, 20% loss of activity
60
-
-
5 min, 50% loss of activity
60
-
-
loss of approx. 60% activity after 20C
60
-
-
more than 90% inactivation after 15 min, half-life: 4 min
60
-
-
10 min, 50% residual activity
62
-
-
melting temperature, catalytic subunit
65
-
-
melting temperature, catalytic subunit, presence of carbamoyl phosphate; melting temperature, holoenzyme
67
-
-
melting temperature, holoenzyme, presence of carbamoyl phosphate
75
-
-
catalytic subunit looses 50% activity after 1 min
75
-
-
catalytic subunit looses 25% activity after 60 min
80
-
-
stable up to
85
-
Q55338
no loss of activity after 15 min
87
-
-
5 min, 50% inactivation
90
-
-
no loss of activity after 6 h
90
-
Q55338
native and recombinant enzyme, loss of less than 10% activity after 40 min
90
-
-
catalytic subunit, half-life: 80 min, half-life of holenzyme: 240 min
90
-
-
half-life 260 min
94
-
-
half-life 190 min
95
-
-
30 min, stable in solutes, but large loss of secondary structure in absence of solutes, the loss is enhanced in presence of KCl, NaCl, or K+-glutamate, glycine and sucrose are thermoprotective
98
-
-
half-life of the holoenzyme is 2.5 times higher than that of the catalytic subunit
98
-
-
half-life 100 min
100
-
-
30 min, stable in solutes, but loss of 41% of secondary structure in absence of solutes, the loss is enhanced in presence of KCl, NaCl, or K+-glutamate, glycine and sucrose are thermoprotective
additional information
-
-
carboxylic acids e.g. acetic acid, citric acid and high ionic strength, 200 mM KCl, protect against thermal denaturation at 65-70C
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
carbamoyl phosphate protects against proteolysis
-
carboxylic acids, e.g. acetic acid, citric acid and high ionic strength, 200 mM KCl, protect against thermal denaturation at 65-70C
-
unstable in very dilute solutions
-
chemical stabilization of conformational states of enzyme
-
thermal denaturation
-
dimethylsulfoxid and glycerol are required to stabilize the enzyme
-
carbamoyl phosphate protects against thermal denaturation
-
freezing and thawing in 50 mM Tris-HCl buffer, pH 7.4, 1 mM 2-mercaptoethanol has no effect on stability
-
50% glycerol stabilizes
-
cold-labile when highly purified, must be stored at room temperature, complete loss of activity after 24 h at pH 7.0 and 0C
-
phosphate required for maximum stability
-
presence of 20 mM potassium phosphate as well as 10% v/v glycerol is required for maintenance of activity of the purified enzyme
-
purified enzyme is inactivated if stored frozen
-
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-10C -20C, many months, no loss of activity
-
-20C, 0.1-1 mg protein/ml, at least 2 years, no loss of activity 4C, 0.1-1 mg/ml, at least 2 months, no loss of activity
-
4C, mercaptoethanol-imidazole buffer, several months
-
-20C, 35 days, loss of 50% activity
-
-80C, 35 days, stable
-
-20C, 2 mM carbamoyl phosphate, 1 mM 2-mercaptoethanol, at least a week, no loss of activity
-
4C, 50 mM Tris-HCl, pH 7.5, 25% glycerol, 3 mM sodium azide, indefinitely, no loss of activity
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
recombinant enzyme
-
protamine sulfate, heat treatment, ammonium sulfate, Sephadex G-150, DEAE-Sephadex, DEAE-cellulose
-
Q-Sepharose, Matrex gel Red A, Matrex Phenyl Cellufine
-
recombinant enzyme from Escherichia coli strain EK114 by anion exchange chromatography, ammonium sulfate fractionation, and hydrophobic interaction chromatography
-, P05654
pH 4.8, hydroxylapatite, ammonium sulfate, DEAE-Sephadex
-
heat, ammonium sulfate, DEAE-cellulose
-
rapid procedure
-
recombinant enzyme from Escherichia coli strain EK114 by anion exchange chromatography, ammonium sulfate fractionation, and hydrophobic interaction chromatography
-
recombinant His6-tagged enzyme
-
recombinant wild-type and mutant enzymes from Escherichia coli strain EK1104 by isoelectric precipitation, anion exchange, and hydrophobic interaction chromatography, and gel filtration
-
aspartate transcarbamoylase activity domain of the multienzyme complex
-
multienzyme complex
-
heat, Q-Sepharose, Phenyl-Sepharose
-
streptomycin sulfate, ammonium sulfate, DE-52 column, Sephadex G-200, aspartate linked CNBr
-
recombinant enzyme, Ni2+-affinity column
-
Streptomycin sulfate, ammonium sulfate, Sephadex G-200, hydroxylapatite, preparative gel electrophoresis
-
ion-exchange, gel filtration
-
multienzyme complex
-
CaCl2, heat, ethanol, 10-carboxydecylamino-Sepharose, DEAE-cellulose
-
ethanol, 10-carboxydecyl-Sepharose, DEAE-cellulose
-
purification steps at room temperatur
-
native and recombinant enzyme
-
ammonium sulfate, aspartate-Sepharose
-
ammonium sulfate, DEAE-cellulose, DEAE-Sephadex, Sephadex G-200, partially purified
-
MnSO4, ammonium sulfate, DEAE-cellulose, Sephadex G-100
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expression in Escherichia coli
-
expression in Escherichia coli strain BL21
-, O66726
ATCase overexpression in Escherichia coli strain strain EK1104
-, P05654
overexpression in Escherichia coli
-
crystallized by the microdialysis method. The structures are determined by X-ray crystallography at 2.15 resolution for His20Ar (histidine 20 of the regulatory (r) chain mutated to alanine) and and 2.75 A resolution for Asp19Ar (asparagine 19 of the regulatory (r) chain mutated to alanine)
-
expression of wild-type and mutant enzymes in Escherichia coli strain EK1104 containing the plasmid pEK695
-
overexpression in Escherichia coli
-
overexpression in Escherichia coli strain EK1104 transformed with plasmid pEK15212 containing the Escherichia coli pyrBI gene
-
expression of the catalytic trimer in Escherichia coli strain EK1911, which has a deletion in the pyrBI region of the chromosome and contains plasmids pEK406 coding for the Methanococcus jannaschii ATCase catalytic chain and pSJS1240; expression of the regulatiry subunit in Escherichia coli ATCase-deficient derivative strain C600 which contains T7 RNA polymerase gene under lacUV5 control as a lambda lysogen
Q58801, Q58976
expression in Escherichia coli
-
expression of catalytic subunit in Escherichia coli
-
; expression in Escherichia coli
Q55338
coexpression of carbamoylphosphate synthetase II, aspartate transcarbamoylase, and dihydroorotase in Escherichia coli
-
expression in Eshcerichia coli
-
expression in Escherichia coli
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
A241C
-
reduced affinity for aspartate, hyperbolic aspartate saturation curve
C47A
-
Hill coefficient 1.3 as compared to 2.4 for wild-type
C47A/A241C
-
non-reducing conditions, reduced affinity for aspartate, hyperbolic aspartate saturation curve
C47A/A241C
-
the mutant holoenzyme with disulfides intact displays a hyperbolic Asp saturation curve confirming the loss of homotropic cooperativity, phosphate binding structure of the mutant, overview
D162A
-
7700fold reduction in specific activity, 2fold decrease in affinity for aspartate, loss of homotropic cooperativity and decreased activation by ATP
D19A
-
loss of the synergistic inhibition of UTP in the presence of CTP
D19A
-
a regulatory mutant, which does not exhibit UTP synergistic inhibition
D236A
-
the small-angle x-ray scattering pattern of unliganded D236A ATCase differs from the scattering pattern of the wild-type enzyme
D236A
-
mutation in the catalytic subunit, the mutation substantially destabilize the T state of the enzyme
D236A
-
site-directed mutagenesis, 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
E239Q
-
mutation in the catalytic subunit, the mutation substantially destabilize the T state of the enzyme
E50A
-
mutant enzyme shows a low activity, low affinity state, only 2fold activation with N-(phosphonoacetyl)-L-aspartate, kinetic mechanism is changed
E50A
-
shift of equilibrium toward unliganded T-state, crystallization analysis
H20A
-
the mutation results in the complete loss of synergistic inhibition by UTP
H20A
-
a regulatory mutant, which does not exhibit UTP synergistic inhibition
K143A
-
mutation in the regulatory subunit, the mutation substantially destabilize the T state of the enzyme
K164E/E239K
-
site-directed mutagenesis, a mutant aspartate transcarbamoylase exists in an intermediate quaternary structure between the canonical T and R structures, crystal structure and quaternary conformation analysis, detailed overview. pH-Dependent structural alteration consistent with either a pH-induced conformational change or a pH-induced alteration in the T to R equilibrium
K244A
-
dramatic reduction in homotropic cooperativity and the ability of heterotropic effectors to modulate activity
K244N
-
dramatic reduction in homotropic cooperativity and the ability of heterotropic effectors to modulate activity
K56A
-
the mutation results in the complete loss of synergistic inhibition by UTP
K56A
-
a regulatory mutant, which does not exhibit UTP synergistic inhibition
K60A
-
a regulatory mutant, which does not exhibit UTP synergistic inhibition
K6A
-
a regulatory mutant, which does not exhibit UTP synergistic inhibition
L151Q
-
strongly reduced stimulation by ATP, synergistic inhibition by UTP is decreased
L151V
-
stimulation by ATP is reduced by 50%
L32A
-
stimulation by ATP is reduced by 25%
L76A
-
synergistic inhibition by UTP is decreased
L7A
-
a regulatory mutant, which does not exhibit UTP synergistic inhibition
N111A
-
mutation in the regulatory subunit, the mutation substantially destabilize the T state of the enzyme
P268A
-
40fold reduction in activity, concentration of N-(phosphonoacetyl)-L-aspartate for maximal activation is increased 233fold as compared to the wild-type, less activation by ATP, stronger inhibition by CTP
Q137A
-
no induction of induced fit by substrates, enzyme is lockd in the low-activity, low affinity T-state
Q137A
-
the concentration of carbamoyl phosphate required to attain one half of the maximal activity increases by 210fold, the corresponding value for aspartate increases by 76fold, extremely reduced affinity for carbamoyl phosphate and near abolition of aspartate binding compared to the wild-type enzyme
Q73E
-
stimulation by ATP is reduced by 80%
V106A
-
synergistic inhibition by UTP is decreased
V106W
-
strongly reduced stimulation by ATP
V106W/Y77F
-
strongly reduced stimulation by ATP
Y165F
-
mutant enzyme shows greatly reduced affinity for aspartate and activity
Y240F
-
mutant enzyme shows higher affinity for aspartate and increased activity
additional information
-, O66726
in noncovalent association with dihydroorotase, possible model for mammalian polypeptide chain CPSase/ATCase/DHOase during pyrimidine biosynthesis
Y77F
-
synergistic inhibition by UTP is decreased
additional information
-
chimeric enzyme consisting of E.coli catalytic subunit and Serratia marcescens regulatory subunit
Renatured/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
4% of original activity is restored
-
dialysis after SDS-denaturation, 1% of original activity is restored
-