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Literature summary extracted from

  • Kantrowitz, E.R.
    Allostery and cooperativity in Escherichia coli aspartate transcarbamoylase (2012), Arch. Biochem. Biophys., 519, 81-90.
    View publication on PubMedView publication on EuropePMC

Activating Compound

EC Number Activating Compound Comment Organism Structure
2.1.3.2 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 Escherichia coli

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
2.1.3.2 X-ray structures of wild-type Escherichia coli aspartate transcarbamoylase holoenzyme and catalytic subunit crystallized with different ligands, overview Escherichia coli

Protein Variants

EC Number Protein Variants Comment Organism
2.1.3.2 D236A mutation in the catalytic subunit, the mutation substantially destabilize the T state of the enzyme Escherichia coli
2.1.3.2 E239Q mutation in the catalytic subunit, the mutation substantially destabilize the T state of the enzyme Escherichia coli
2.1.3.2 K143A mutation in the regulatory subunit, the mutation substantially destabilize the T state of the enzyme Escherichia coli
2.1.3.2 N111A mutation in the regulatory subunit, the mutation substantially destabilize the T state of the enzyme Escherichia coli

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.1.3.2 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 Escherichia coli

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
2.1.3.2 additional information
-
 additional information aspartate transcarbamoylase is an allosteric enzyme, quaternary structural changes during the allosteric transition, and kinetics of the allosteric transition, overview Escherichia coli

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.1.3.2 L-aspartate + carbamoyl phosphate Escherichia coli
-
 phosphate + N-carbamoyl-L-aspartate i.e. ureidosuccinic acid ?

Organism

EC Number Organism UniProt Comment Textmining
2.1.3.2 Escherichia coli
-
-
-

Reaction

EC Number Reaction Comment Organism Reaction ID
2.1.3.2 carbamoyl phosphate + L-aspartate = phosphate + N-carbamoyl-L-aspartate 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 Escherichia coli
a

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.1.3.2 L-aspartate + carbamoyl phosphate
-
 Escherichia coli phosphate + N-carbamoyl-L-aspartate
-
 ?
2.1.3.2 L-aspartate + carbamoyl phosphate
-
 Escherichia coli phosphate + N-carbamoyl-L-aspartate i.e. ureidosuccinic acid ?

Subunits

EC Number Subunits Comment Organism
2.1.3.2 dodecamer quaternary structural changes during the allosteric transition, overview Escherichia coli

Synonyms

EC Number Synonyms Comment Organism
2.1.3.2 aspartate transcarbamoylase
-
 Escherichia coli
2.1.3.2 ATCase
-
 Escherichia coli

General Information

EC Number General Information Comment Organism
2.1.3.2 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 Escherichia coli
2.1.3.2 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 Escherichia coli