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Literature summary for 2.1.3.2 extracted from

  • Lipscomb, W.N.; Kantrowitz, E.R.
    Structure and mechanisms of Escherichia coli aspartate transcarbamoylase (2012), Acc. Chem. Res., 45, 444-453.
    View publication on PubMedView publication on EuropePMC

Activating Compound

Activating Compound Comment Organism Structure
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 Escherichia coli

Crystallization (Commentary)

Crystallization (Comment) Organism
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 Escherichia coli

Protein Variants

Protein Variants Comment Organism
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 Escherichia coli

Inhibitors

Inhibitors Comment Organism Structure
CTP ATCase is feedback inhibited by CTP and synergistically by the combination of CTP plus UTP Escherichia coli
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 Escherichia coli

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
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 Escherichia coli

Metals/Ions

Metals/Ions Comment Organism Structure
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 Escherichia coli

Molecular Weight [Da]

Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
30000
-
x * 96000 + x * 30000 Escherichia coli
96000
-
x * 96000 + x * 30000 Escherichia coli
310000
-
-
Escherichia coli

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
L-aspartate + carbamoyl phosphate Escherichia coli
-
phosphate + N-carbamoyl-L-aspartate
-
?

Organism

Organism UniProt Comment Textmining
Escherichia coli
-
-
-

Reaction

Reaction Comment Organism Reaction ID
carbamoyl phosphate + L-aspartate = phosphate + N-carbamoyl-L-aspartate 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 Escherichia coli

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
L-aspartate + carbamoyl phosphate
-
Escherichia coli phosphate + N-carbamoyl-L-aspartate
-
?

Subunits

Subunits Comment Organism
heterooligomer x * 96000 + x * 30000 Escherichia coli
More 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 Escherichia coli

Synonyms

Synonyms Comment Organism
aspartate transcarbamoylase
-
Escherichia coli
ATCase
-
Escherichia coli

General Information

General Information Comment Organism
metabolism ATCase regulates the pyrimidine nucleotide biosynthesis by feedback control and by the cooperative binding of the substrate L-aspartate Escherichia coli
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 Escherichia coli