Information on EC 6.3.5.5 - Carbamoyl-phosphate synthase (glutamine-hydrolysing)

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY
6.3.5.5
-
RECOMMENDED NAME
GeneOntology No.
Carbamoyl-phosphate synthase (glutamine-hydrolysing)
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
2 ATP + HCO3- + NH3 = 2 ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
-
2 ATP + L-glutamine + HCO3- + H2O + H+ = 2 ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
-
-
-
-
2 ATP + L-glutamine + HCO3- + H2O + H+ = 2 ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
carbamate, the product of the reaction involving ATP, bicarbonate, and ammonia, must be delivered from the site of formation to the site of utilization by traveling nearly 40 A within the enzyme. The tunnel is composed of three continuous water pockets and two narrow connecting parts, near residues A23 and G575. The two narrow parts render two free energy barriers of 6.7 and 8.4 kcal/mol, respectively. Three water pockets are filled with about 21, 9, and 9 waters, respectively, and the corresponding relative free energies of carbamate residing in these free energy minima are 5.8, 0, and 1.6 kcal/mol, respectively. The release of phosphate into solution at the site for the formation of carbamate allows the side chain of R306 to rotate toward E25, E383, and E604. This rotation is virtually prohibited by a barrier of at least 23 kcal/mol when phosphate remains bound. This conformational change not only opens the entrance of the tunnel but also shields the charge-charge repulsion from the three glutamate residues when carbamate passes through the tunnel
P00968
2 ATP + L-glutamine + HCO3- + H2O = 2 ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
-
-
-
-
2 ATP + L-glutamine + HCO3- + H2O = 2 ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
mechanism, formation of enzyme-bound carboxy phosphate
-
2 ATP + L-glutamine + HCO3- + H2O = 2 ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
partially random sequential mechanism in which the ordered addition of MgATP2- , HCO3-, and Gln is followed by the ordered release of Glu and phosphate. The formation of carbamate from MgATP2-, HCO3-, and Gln proceeds via a stepwise, not concerted mechanism, involving at least one kinetically competent covalent intermediate, such as carboxyphosphate
-
2 ATP + L-glutamine + HCO3- + H2O = 2 ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
mechanism involves at least three steps, the first of which is an ATP-dependent formation of enzyme-bound activated carbon dioxide
-
2 ATP + L-glutamine + HCO3- + H2O = 2 ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
reaction pathway of the enzyme small subunit proceeds through the formation of the glutamyl thioester intermediate
-
2 ATP + L-glutamine + HCO3- + H2O = 2 ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
steps of reaction pathway for glutamine hydrolysis, the Michalis complex, the tetrahedral intermediate and glutamyl-thioester intermediate models, stereochemistry of the overall glutaminase reaction
-
2 ATP + L-glutamine + HCO3- + H2O = 2 ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
four partial reaction occurs at three active sites connected by a molecular tunnel of 100 Angstrom, reaction mechanism
-
2 ATP + L-glutamine + HCO3- + H2O = 2 ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
An ordered uni bi mechanism for glutamine hydrolysis that is consistent with the isotope effects and with the catalytic properties of the enzyme is proposed
-
2 ATP + L-glutamine + HCO3- + H2O = 2 ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
catalytic mechanism
-
2 ATP + L-glutamine + HCO3- + H2O = 2 ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
the chemical mechanism of the bicarbonate-dependent ATPase reaction of enzyme involves carboxy phosphate, but not CO2, as an reactive intermediate
-
2 ATP + L-glutamine + HCO3- + H2O = 2 ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
pathway, relationship between mechanism and structure
-
2 ATP + L-glutamine + HCO3- + H2O = 2 ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
pathway
-
2 ATP + L-glutamine + HCO3- + H2O = 2 ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
effects of pressure on the partial reactions, study of the function of monomers of enzyme domains under conditions of pressure-induced dissociation
-
2 ATP + L-glutamine + HCO3- + H2O = 2 ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
the mammalian enzyme is part of carbamoyl-phosphate synthase-aspartate carbamoyltransferase-dihydroorotase, CAD, the carbamoyl phosphate synthesis requires the concerted action of the glutaminase and carbamoyl-phosphate synthetase domains of CAD
-
2 ATP + L-glutamine + HCO3- + H2O = 2 ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
mechanism
-
2 ATP + L-glutamine + HCO3- + H2O = 2 ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
in glutamine utilizing enzymes, the hydrolysis of glutamine to yield ammonia is catalyzed at a triad-type glutamine amidotransferase domain
-
2 ATP + L-glutamine + HCO3- + H2O = 2 ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
two residues, Ser948 and Thr1042, appear crucial for allosteric regulation of enzyme
-
2 ATP + L-glutamine + HCO3- + H2O = 2 ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
reaction mechanism, the ammonium is channeled as ammonia through a channel formed by the small subunit by forming and breaking hydrogen bonds to Gly292, Ser35, Pro358, Gly293, and Thr37 in a stepwise fashion as it travels through the hydrophilic passage toward the subunit interface
-
2 ATP + L-glutamine + HCO3- + H2O = 2 ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
mechanism for the generation of ammonia within the L-glutamine amidotransferase domain of CPS, detailed overview
-
2 ATP + L-glutamine + HCO3- + H2O = 2 ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
reaction mechanism with four separate reactions and three discrete, reactive, and unstable intermediates involved, overview. The small subunit contains the active site for the hydrolysis of glutamine, which is hydrolyzed to glutamate and ammonia via a thioester intermediate. The ammonia derived from this reaction travels 45 A to the active site for the synthesis of the carboxy phosphate intermediate, located in the N-terminal half of the large subunit. The carbamate intermediate, formed by the reaction of ammonia with carboxy phosphate, is subsequently channeled 45 A to the active site, located at the C-terminus of the large subunit, for the synthesis of carbamoyl phosphate, which is phosphorylated by the second molecule of MgATP to form the ultimate product carbamoyl phosphate. Molecular dynamics simulations, kinetic and dynamic of the mechanism for ammonia migration at the atomic level, free-energy profile for the remainder of the ammonia tunnel within CPS using the umbrella sampling technique, overview
-
L-glutamine + H2O = L-glutamate + NH3
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
amide group transfer
-
-
-
-
amination
-
-
-
-
Phosphorylation
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
Alanine, aspartate and glutamate metabolism
-
arginine biosynthesis I (via L-ornithine)
-
arginine biosynthesis II (acetyl cycle)
-
arginine biosynthesis III (via N-acetyl-L-citrulline)
-
arginine biosynthesis IV (archaebacteria)
-
Metabolic pathways
-
Pyrimidine metabolism
-
UMP biosynthesis
-
SYSTEMATIC NAME
IUBMB Comments
hydrogen-carbonate:L-glutamine amido-ligase (ADP-forming, carbamate-phosphorylating)
The product carbamoyl phosphate is an intermediate in the biosynthesis of arginine and the pyrimidine nucleotides [4]. The enzyme from Escherichia coli has three separate active sites, which are connected by a molecular tunnel that is almost 100 A in length [8]. The amidotransferase domain within the small subunit of the enzyme hydrolyses glutamine to ammonia via a thioester intermediate. The ammonia migrates through the interior of the protein, where it reacts with carboxy phosphate to produce the carbamate intermediate. The carboxy-phosphate intermediate is formed by the phosphorylation of bicarbonate by ATP at a site contained within the N-terminal half of the large subunit. The carbamate intermediate is transported through the interior of the protein to a second site within the C-terminal half of the large subunit, where it is phosphorylated by another ATP to yield the final product, carbamoyl phosphate [6].
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
CAD carbamoyl-phosphate synthetase
-
-
CAD protein
-
-
Carbamoyl phosphate synthase (glutamine)
-
-
-
-
carbamoyl phosphate synthetase
-
-
carbamoyl phosphate synthetase
Deinococcus radiophilus NCIMB 10648
-
-
-
carbamoyl phosphate synthetase
-
-
carbamoyl phosphate synthetase
-
-
carbamoyl phosphate synthetase
Sulfolobus acidocaldarius DG6
-
-
-
Carbamoyl phosphate synthetase (glutamine-hydrolyzing)
-
-
-
-
carbamoyl phosphate synthetase 1
-
-
carbamoyl phosphate synthetase II
-
-
carbamoyl phosphate synthetase III
-
-
carbamoyl-phosphate synthetase
-
-
carbamoyl-phosphate synthetase
-
-
Carbamoyl-phosphate synthetase (glutamine-hydrolysing)
-
-
-
-
carbamoyl-phosphate synthetase 2
-
-
Carbamoylphosphate synthase
-
-
-
-
Carbamoylphosphate synthase
-
-
Carbamoylphosphate synthetase
-
-
-
-
Carbamoylphosphate synthetase
-
-
Carbamoylphosphate synthetase
-, B9V284
-
Carbamoylphosphate synthetase II
-
-
-
-
Carbamoylphosphate synthetase II
-
-
Carbamyl phosphate synthetase (glutamine)
-
-
-
-
Carbamyl phosphate sythetase II
-
-
-
-
carbamylphosphate synthetase - aspartate transcarbamylase
-
multifunctional protein
CPS
-
-
-
-
CPS
Sulfolobus acidocaldarius DG6
-
-
-
CPS II (glutamine-dependent)
-
-
CPS III (glutamine- and N-acetyl-L-glutamine-dependent)
-
-
CPSase
-
-
-
-
CPSase
Deinococcus radiophilus NCIMB 10648
-
-
-
CPSase type II
-
-
CPSase-A
-
-
-
-
CPSase-P
-
-
-
-
EC 2.7.2.9
-
-
formerly
-
Glutamine-dependent carbamyl phosphate synthetase
-
-
-
-
MtCPSs1
B9V284
-
Synthase, carbamoylphosphate (glutamine)
-
-
-
-
Synthetase, carbamoylphosphate (glutamine-hydrolyzing)
-
-
-
-
glutamine-hydrolyzing CPSase
-
-
additional information
-
carbamoyl phosphate synthetase is a member of the amidotransferase family of enzymes
CAS REGISTRY NUMBER
COMMENTARY
37233-48-0
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
genes carA and carB encoding the small and large subunit of the CPSase
-
-
Manually annotated by BRENDA team
Deinococcus radiophilus NCIMB 10648
NCIMB 10648
-
-
Manually annotated by BRENDA team
supressor of black mutation
Uniprot
Manually annotated by BRENDA team
and construction of a chimeric enzyme, in which the C-terminal 136 residues of Escherichia coli enzyme are replaced by the corresponding residues of Saccharomyces cerevisiae enzyme
-
-
Manually annotated by BRENDA team
large subunit
UniProt
Manually annotated by BRENDA team
strain B
-
-
Manually annotated by BRENDA team
wild type and mutant enzymes
-
-
Manually annotated by BRENDA team
Escherichia coli L814
L814
-
-
Manually annotated by BRENDA team
possess 2 carbamoyl-phosphate synthases, one belonging to the arginine pathway, CPSase-A, and another belonging to the pyrimidine pathway, CPSase-P
-
-
Manually annotated by BRENDA team
Fresh-water teleost
-
-
-
Manually annotated by BRENDA team
Blackmous catshark
-
-
Manually annotated by BRENDA team
2 carbamoyl-phosphate synthases, one specific for pyrimidine biosynthesis and the other for arginine biosynthesis
-
-
Manually annotated by BRENDA team
wild-type and mutant strain
Q8RSS4 and Q8RSS3
UniProt
Manually annotated by BRENDA team
HCV, gene CAD
-
-
Manually annotated by BRENDA team
atlantic halibut, yolk-sac larvae and adult, two enzymes: CPS II and CPS III
-
-
Manually annotated by BRENDA team
multifunctional protein, catalyzing the first three steps in de novo pyrimidine biosynthesis
-
-
Manually annotated by BRENDA team
multifunctional protein, catalyzing the first three steps in de novo pyrimidine biosynthesis
-
-
Manually annotated by BRENDA team
Syrian hamster
-
-
Manually annotated by BRENDA team
derepressed strain
-
-
Manually annotated by BRENDA team
carbamoyl-phosphate-synthase/aspartate transcarbamoylase complex
-
-
Manually annotated by BRENDA team
construction of a chimeric enzyme, in which the C-terminal 136 residues of Escherichia coli enzyme are replaced by the corresponding residues of Saccharomyces cerevisae enzyme
-
-
Manually annotated by BRENDA team
carB; DSM20617, gene carB
UniProt
Manually annotated by BRENDA team
Streptomyces lividans MTCC1
MTCC1
-
-
Manually annotated by BRENDA team
Sulfolobus acidocaldarius DG6
-
-
-
Manually annotated by BRENDA team
strains cps1-1 and RH
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
metabolism
-
the enzyme is organized as CAD, i.e. carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase, a tripartite enzyme that catalyzes the first three steps of pyrimidine biosynthesis
physiological function
-
carbamoylphosphate synthetase plays a specific physiological role in ammonium assimilation in the mesophyll and phloem for the synthesis and transport of glutamine, glutamate, and derived amino acids, overview
physiological function
B2G3Q3
carbamoylphosphate synthetase activity is essential for the optimal growth and acidification of Streptococcus thermophilus in cow milk
physiological function
-
the enzyme is essential for HCV infection and replication in human liver cells
physiological function
-
a single carbamoyl phosphate synthetase supplies both the pyrimidine and arginine pathways of this organism
physiological function
Sulfolobus acidocaldarius DG6
-
a single carbamoyl phosphate synthetase supplies both the pyrimidine and arginine pathways of this organism
-
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2 ATP + L-Gln + HCO3- + H+ + H2O
2 ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
P00968
-
-
-
?
2 ATP + L-Gln + HCO3- + H+ + H2O
2 ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
-
the product carbamoyl phosphate is utilized in the pyrimidine and arginine biosynthetic pathways
-
?
2 ATP + L-glutamine + HCO3- + H2O
2 ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
-
-
-
-
?
2 ATP + L-glutamine + HCO3- + H2O
2 ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
-
-
-
-
?
2 ATP + L-glutamine + HCO3- + H2O
2 ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
B2G3Q3
-
-
-
?
2 ATP + L-glutamine + HCO3- + H2O
2 ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
-
-
carbamoyl phosphate is utilized in the biosynthesis of arginine and pyrimidine nucleotides
-
?
2 ATP + L-glutamine + HCO3- + H2O + H+
2 ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
-
-, a single carbamoyl phosphate synthetase supplies both the pyrimidine and arginine pathways of this organism
-
-
?
2 ATP + L-glutamine + HCO3- + H2O + H+
2 ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
Sulfolobus acidocaldarius DG6
-
-, a single carbamoyl phosphate synthetase supplies both the pyrimidine and arginine pathways of this organism
-
-
?
ATP + gamma-glutamyl hydrazide + HCO3-
?
show the reaction diagram
-
-
-
?
ATP + gamma-glutamyl hydroxamate + HCO3-
?
show the reaction diagram
-
-
-
?
ATP + hydrazine + HCO3-
ATP + phosphate + N-amino carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + hydroxylamine + HCO3-
ATP + phosphate + N-hydroxy carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
-
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
P05990
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
-
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
-
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
-
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
-
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
-
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
-
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
-
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
-
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
-
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
-
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
-
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
-
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
-
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
-
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
-
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
-
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
-
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
-
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
-
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
-
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
-
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
ir
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
ir
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
ir
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
-
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
-
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
-
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
-
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
-
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
-
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
-
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
-
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
-
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
-
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
-
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
-
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
-
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
-
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
-
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
-
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
-
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
Q8RSS4 and Q8RSS3
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
O15830
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
O15829
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
O50302
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
overall reaction is irreversible
-
-
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
enzyme catalyses the first step of urea cycle in fish
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
enzyme is a key enzyme in the pyrimidine nucleotide and arginine biosynthetic pathways
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
enzyme is a key enzyme in the pyrimidine nucleotide and arginine biosynthetic pathways
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
enzyme is a key enzyme in the pyrimidine nucleotide and arginine biosynthetic pathways
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
enzyme is a key enzyme in the pyrimidine nucleotide and arginine biosynthetic pathways
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
Q8RSS4 and Q8RSS3
enzyme is a key enzyme in the pyrimidine nucleotide and arginine biosynthetic pathways, possible role in the pathway for the synthesis of exopolysaccharides
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
the enzyme catalyses the entry and rate-limiting step of the urea cycle
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
O50302
the enzyme catalyses the first step in the arginine and pyrimidine biosynthesis
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
the enzyme catalyses the first step in the synthesis of arginine and pyrimidine
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
the product carbamoyl phosphate is an essential precursor of arginine and pyrimidine biosynthesis
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
the product carbamoyl phosphate is an essential precursor of arginine and pyrimidine biosynthesis
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
the product carbamoyl phosphate is an essential precursor of arginine and pyrimidine biosynthesis
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
the product carbamoyl phosphate is the initial intermediate in the biosynthesis of both pyrimidine and arginine
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
the product carbamoyl phosphate is utilized for the arginine biosynthesis
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
the product carbamoyl phosphate is utilized for the arginine biosynthesis
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
the product carbamoyl phosphate is utilized for the arginine biosynthesis
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
the product carbamoyl phosphate plays a critical role in both arginine and pyrimidine biosynthesis
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
the product carbamoyl phosphate plays a critical role in both arginine and pyrimidine biosynthesis
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
the product carbamoylphosphate is utilized in the synthesis of arginine and pyrimidine nucleotides and in the urea cycle
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
carbamoyl phosphate synthetase contains an internal molecular tunnel, which has been proposed to facilitate the translocation of reaction intermediates from one active site to another. Ammonia, the product from the hydrolysis of glutamine in the small subunit, is apparently transported to the next active site in the large subunit of CPS over a distance of about 45 . The ammonia tunnel that connects these two active sites provides a direct path for the guided diffusion of ammonia and protection from protonation
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
cross-talk between domain N and C is required for product release from subunit C
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
Escherichia coli L814
-
-, enzyme is a key enzyme in the pyrimidine nucleotide and arginine biosynthetic pathways
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
Streptomyces lividans MTCC1
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
Saccharomyces cerevisiae LPL26
-
-, the product carbamoyl phosphate is utilized for the arginine biosynthesis
-
?
ATP + L-Gln + HCO3-
?
show the reaction diagram
-
functions in the synthesis of urea used in osmoregulation
-
-
-
ATP + L-Gln + HCO3-
?
show the reaction diagram
-
important role of insulin in regulation of liver carbamoyl-phosphate synthase II and lack of responsiveness of the hepatoma enzyme to insulin concentration
-
-
-
ATP + L-Gln + HCO3-
?
show the reaction diagram
-
catalyzes the first step of de novo pyrimidine biosynthesis
-
-
-
ATP + L-Gln + HCO3-
?
show the reaction diagram
-
catalyzes the first step of de novo pyrimidine biosynthesis
-
-
-
ATP + L-Gln + HCO3-
?
show the reaction diagram
-
catalyzes the first step of de novo pyrimidine biosynthesis
-
-
-
ATP + L-Gln + HCO3-
?
show the reaction diagram
-
catalyzes the synthesis of all carbamoyl phosphate which serves two metabolic functions: it is an intermediate in synthesis of arginine and in the synthesis of pyrimidines
-
-
-
ATP + L-glutamine + HCO3- + H2O
ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
-
-
-
-
?
ATP + L-glutamine + HCO3- + H2O
ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
-
-
-
-
?
ATP + L-glutamine + HCO3- + H2O
ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
-
-, allosteric regulation and CPSII regulatory domains, overview
-
-
?
ATP + L-glutamine + HCO3- + H2O
ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
-
CPS1 plays a critical role in the biosynthesis of pyrimidine nucleotides and the detoxification of ammonia
-
-
?
ATP + L-glutamine + HCO3- + H2O
ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
-
evolutionarily conserved triad glutamine amidotransferase, GAT, domains catalyze the cleavage of L-glutamine to yield ammonia and sequester the ammonia in a tunnel until delivery to a variety of acceptor substrates in synthetase domains of variable structure. The Cys269 and His353 catalytic triad residues are essential for L-glutamine hydrolysis, whereas Glu355 is not critical for eCPS activity, Gln351 plays a key role in L-glutamine binding, overview
-
-
?
ATP + L-glutamine + HCO3- + H2O
ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
-
neither residue P909 nor residue G919 is critical for eCPS function due to the absence of vicinal cysteinyl residues in wild-type eCPS
-
-
?
ATP + L-glutamine + HCO3- + H2O
ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
-
substrate-channelling, the enzyme is also active with NH3 as nitrogen source, cf. EC 6.3.4.16
-
-
?
ATP + L-glutamine + HCO3- + H2O
ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
-
the enzyme from Escherichia coli catalyzes the synthesis of carbamoyl phosphate from bicarbonate, glutamine, and two molecules of ATP via a chemical mechanism that involves four separate reactions and three unstable intermediates, e.g. carboxyphosphate and carbamate
-
-
r
ATP + L-glutamine + HCO3- + H2O
ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
Deinococcus radiophilus NCIMB 10648
-
-, substrate-channelling, the enzyme is also active with NH3 as nitrogen source, cf. EC 6.3.4.16
-
-
?
ATP + L-glutamine + HCO3- + H2O
2 ADP + phosphate + L-glutamate + carbamoyl phosphate
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
-
-
?
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
-
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
-
-
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
-
?
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
ir
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
-
-
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
-
-
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
-
-
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
-
-
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
Q8RSS4 and Q8RSS3
-
-
?
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
utilizes NH4+ with 600times lower affinity than Gln
-
-
-
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
CPS III shows low activity in comparison to L-glutamine
-
?
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
-
the enzyme is able to utilize external NH4+ as an alternative nitrogen source when glutamine is absent
-
-
?
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
Escherichia coli L814
-
-
-
?
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
Streptomyces lividans MTCC1
-
-
-
?
ATP + NH4+ + HCO3-
ADP + phosphate + carbamoyl phosphate
show the reaction diagram
Saccharomyces cerevisiae LPL26
-
-
-
?
additional information
?
-
-
hydrolysis of L-Gln in absence of the other substrates, at 5.9% the rate of glutamine hydrolysis in the complete system
-
-
-
additional information
?
-
-
existence of an alternate route to the bicarbonate phosphorylation site when ammonia is provided as an external nitrogen source
-
?
additional information
?
-
-
the gene for carbamoylphosphate synthetase (carAB) is induced by FlhD and FlhC
-
-
-
additional information
?
-
-
CPS uses the hydrolysis of glutamine as a localized source of ammonia for biosynthetic transformations
-
-
-
additional information
?
-
-
assay method development based on the fixation of 14C from the substrate bicarbonate to give radioactive products. In the coupled assay the carbamoyl phosphate product of the enzyme is converted to carbamoyl aspartate in the presence of aspartate and aspartate transcarbamoylase, substrate-channelling between aspartate aminotransferase and CPSase, overview
-
-
-
additional information
?
-
-
the smaller subunit contains the binding site for the hydrolysis of glutamine, whereas the large subunit catalyzes the formation of carbamoyl phosphate. Molecular dynamics simulations and free-energy profile for the transfer of ammonia and ammonium through a tunnel in the small subunit of CPS, by use of the enzyme's crystal structure, resulting in five successful trajectories for ammonia transfer, while ammonium is immobilized in a water pocket inside the small subunit of the heterodimeric protein, the carbamate tunnel connects the two active sites within the large subunit to one another and guides the unstable carbamate intermediate to the site of phosphorylation, mechanism, overview
-
-
-
additional information
?
-
-
the enzyme is organized as CAD, i.e. carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase, a tripartite enzyme that catalyzes the first three steps of pyrimidine biosynthesis
-
-
-
additional information
?
-
Deinococcus radiophilus NCIMB 10648
-
assay method development based on the fixation of 14C from the substrate bicarbonate to give radioactive products. In the coupled assay the carbamoyl phosphate product of the enzyme is converted to carbamoyl aspartate in the presence of aspartate and aspartate transcarbamoylase, substrate-channelling between aspartate aminotransferase and CPSase, overview
-
-
-
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
2 ATP + L-Gln + HCO3- + H+ + H2O
2 ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
-
the product carbamoyl phosphate is utilized in the pyrimidine and arginine biosynthetic pathways
-
?
2 ATP + L-glutamine + HCO3- + H2O
2 ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
-
-
-
-
?
2 ATP + L-glutamine + HCO3- + H2O
2 ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
B2G3Q3
-
-
-
?
2 ATP + L-glutamine + HCO3- + H2O
2 ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
-
-
carbamoyl phosphate is utilized in the biosynthesis of arginine and pyrimidine nucleotides
-
?
2 ATP + L-glutamine + HCO3- + H2O + H+
2 ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
Sulfolobus acidocaldarius, Sulfolobus acidocaldarius DG6
-
a single carbamoyl phosphate synthetase supplies both the pyrimidine and arginine pathways of this organism
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
ir
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
enzyme catalyses the first step of urea cycle in fish
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
enzyme is a key enzyme in the pyrimidine nucleotide and arginine biosynthetic pathways
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
enzyme is a key enzyme in the pyrimidine nucleotide and arginine biosynthetic pathways
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
enzyme is a key enzyme in the pyrimidine nucleotide and arginine biosynthetic pathways
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
enzyme is a key enzyme in the pyrimidine nucleotide and arginine biosynthetic pathways
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
Q8RSS4 and Q8RSS3
enzyme is a key enzyme in the pyrimidine nucleotide and arginine biosynthetic pathways, possible role in the pathway for the synthesis of exopolysaccharides
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
the enzyme catalyses the entry and rate-limiting step of the urea cycle
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
O50302
the enzyme catalyses the first step in the arginine and pyrimidine biosynthesis
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
the enzyme catalyses the first step in the synthesis of arginine and pyrimidine
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
the product carbamoyl phosphate is an essential precursor of arginine and pyrimidine biosynthesis
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
the product carbamoyl phosphate is an essential precursor of arginine and pyrimidine biosynthesis
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
the product carbamoyl phosphate is an essential precursor of arginine and pyrimidine biosynthesis
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
the product carbamoyl phosphate is the initial intermediate in the biosynthesis of both pyrimidine and arginine
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
the product carbamoyl phosphate is utilized for the arginine biosynthesis
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
the product carbamoyl phosphate is utilized for the arginine biosynthesis
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
the product carbamoyl phosphate is utilized for the arginine biosynthesis
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
the product carbamoyl phosphate plays a critical role in both arginine and pyrimidine biosynthesis
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
the product carbamoyl phosphate plays a critical role in both arginine and pyrimidine biosynthesis
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
-
the product carbamoylphosphate is utilized in the synthesis of arginine and pyrimidine nucleotides and in the urea cycle
-
?
ATP + L-Gln + HCO3-
?
show the reaction diagram
-
functions in the synthesis of urea used in osmoregulation
-
-
-
ATP + L-Gln + HCO3-
?
show the reaction diagram
-
important role of insulin in regulation of liver carbamoyl-phosphate synthase II and lack of responsiveness of the hepatoma enzyme to insulin concentration
-
-
-
ATP + L-Gln + HCO3-
?
show the reaction diagram
-
catalyzes the first step of de novo pyrimidine biosynthesis
-
-
-
ATP + L-Gln + HCO3-
?
show the reaction diagram
-
catalyzes the first step of de novo pyrimidine biosynthesis
-
-
-
ATP + L-Gln + HCO3-
?
show the reaction diagram
-
catalyzes the first step of de novo pyrimidine biosynthesis
-
-
-
ATP + L-Gln + HCO3-
?
show the reaction diagram
-
catalyzes the synthesis of all carbamoyl phosphate which serves two metabolic functions: it is an intermediate in synthesis of arginine and in the synthesis of pyrimidines
-
-
-
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
Escherichia coli L814
-
enzyme is a key enzyme in the pyrimidine nucleotide and arginine biosynthetic pathways
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
Streptomyces lividans MTCC1
-
-
-
?
ATP + L-Gln + HCO3-
ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
Saccharomyces cerevisiae LPL26
-
the product carbamoyl phosphate is utilized for the arginine biosynthesis
-
?
ATP + L-glutamine + HCO3- + H2O
ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
-
-
-
-
?
ATP + L-glutamine + HCO3- + H2O
ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
-
-
-
-
?
ATP + L-glutamine + HCO3- + H2O
ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
-
allosteric regulation and CPSII regulatory domains, overview
-
-
?
ATP + L-glutamine + HCO3- + H2O
ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
-
CPS1 plays a critical role in the biosynthesis of pyrimidine nucleotides and the detoxification of ammonia
-
-
?
ATP + L-glutamine + HCO3- + H2O
2 ADP + phosphate + L-glutamate + carbamoyl phosphate
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
-
-
?
ATP + L-glutamine + HCO3- + H2O
ADP + phosphate + L-glutamate + carbamoyl phosphate
show the reaction diagram
Deinococcus radiophilus NCIMB 10648
-
-
-
-
?
additional information
?
-
-
the gene for carbamoylphosphate synthetase (carAB) is induced by FlhD and FlhC
-
-
-
additional information
?
-
-
CPS uses the hydrolysis of glutamine as a localized source of ammonia for biosynthetic transformations
-
-
-
additional information
?
-
-
the enzyme is organized as CAD, i.e. carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase, a tripartite enzyme that catalyzes the first three steps of pyrimidine biosynthesis
-
-
-
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
AMP
-
enhances activity
GDP
-
enhances activity
GMP
-
enhances activity
IDP
-
enhances activity
IMP
-
phosphate decreases activation; stimulates
IMP
-
stimulates
MgUTP2-
-
in presence of high concentrations of dimethyl sulfoxide, MgUTP2- stimulates at low concentrations, while it is inhibitory at higher concentrations
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
K+
-
required for maximal activity
K+
-
optimal concentration: 0.1 M
K+
-
Km: 18 mM; required for maximal activity
Mg2+
-
free Mg2+ is required in addition to MgATP2-
Mg2+
-
requires free Mg2+, optimal concentration: 4-10 mM
Mg2+
-
free Mg2+ is required in addition to MgATP2-; optimal concentration: 5 mM
Mg2+
-
requires high concentrations of MgATP2- for optimal activity, half-maximal velocity at 10 mM MgATP2-
Mg2+
-
MgATP2- or Mg2+ enhances glutaminase activity
Mn2+
-
maximal activity at concentration of Mn2+ approximately equal to the ATP concentration
NH4+
-
can replace K+ in activation
NH4+
-
activates
NH4+
-
positive allosteric effector of Gln-dependent activity, promotes self-association of the enzyme
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
6-Diazo-5-oxonorleucine
-
selective inactivation of Gln-dependent activity
6-Diazo-5-oxonorleucine
-
-
acivicin
-
selective time-dependent inhibition of L-Gln-dependent activity, L-Gln protects the enzyme from inactivation. Stimulation of NH4+-dependent activity
ADP
-
competitive with MgATP2-
Ala
-
inhibits glutamine hydrolysis and Gln-dependent carbamoyl phosphate synthesis
Alkyl hydrazines
-
inhibits Gln-dependent activity, but not NH4+-dependent activity
Arg
-
arginine-specific carbamoyl-phosphate synthase is repressed, pyrimidine-specific enzyme not
arginine
Q8RSS4 and Q8RSS3
-
azaserine
-
selective inactivation of Gln-dependent activity
Carbamoyl phosphate
-
-
Gly
-
10 mM, inhibition of glutaminase activity
guanidine hydrochloride
-
-
H2O2
-
0.2 mM, inhibits Gln-dependent activity. No effect on the activity with NH4+ in carbamoyl-phosphate synthase reaction
hydroxylamine
-
inhibits Gln-dependent activity, but not NH4+-dependent activity; the inhibitory effect is much greater at pH 9 than at pH 6
hydroxylamine
-
inhibits Gln-dependent activity, but not NH4+-dependent activity
Hydroxymercuribenzoate
-
-
-
IMP
-
slight inhibition at 25C
IMP
-
binds with good affinity to the enzyme, small effect below 35C
L-2-Amino-4-oxo-5-chloropentanoate
-
selective inactivation of Gln-dependent activity
L-Cyanate
-
inhibits Gln-dependent activity, but not NH4+-dependent activity
-
L-Glu
-
inhibits glutaminase activity moderately
MgATP2-
-
product inhibition
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
NEM
-
irreversible inactivation of synthetase activity. Increase of glutaminase activity
P1,P5-di(adenosine 5')-pentaphosphate
-
inhibits two partial reactions catalyzed by the enzyme: bicarbonate-dependent ATPase and ATP synthesis from carbamoyl phosphate
Polyamines
-
e.g. spermine, spermidine or putrescine
-
Polyamines
-
inhibition is partially reversed by increasing the concentration of Mg2+ or MgATP2-, or by adding low concentrations of 5-phosphoribosyl 1-diphosphate
-
Polyamines
-
-
-
putrescine
-
-
-
UDP
-
inhibits to a lesser extent than UMP
UMP
-
allosteric inhibition
UMP
-
phosphate increases inhibition
UMP
-
feedback inhibition
UMP
-
inhibition is not reversed by glycerol
UMP
-
feedback inhibition
UMP
-
carbamoyl-phosphate synthase belonging to the pyrimidine pathway, carbamoyl-phosphate synthase belonging to the arginine pathway is not inhibited
UMP
-
strong effect on ATP synthesis reaction
UMP
-
Lys993 is cross-linked with UMP
UMP
-
the inhibitor stabilizes the (alpha,beta)2-dimer of enzyme
UMP
-
not chimeric protein
UMP
-
effect on chimeric enzyme and Escherichia coli enzyme
UMP
-
the nonresponsive enzyme can bind UMP at domain D and allosteric effect on chimeric enzyme
UMP
-
only CPS II
UMP
-
the IMP activator and the UMP inhibitor bind to the same site on the enzyme
UMP
-
product of the pyrimidine nucleotide pathway, acts as a negative allosteric effector for eCPS, which also catalyzes the first step of this pathway
Uracil
Q8RSS4 and Q8RSS3
-
UTP
-
inhibits to a lesser extent than UMP
UTP
-
when L-glutamine is the substrate: 94% inhibition of enzyme activity peak 1: CPS II, 6% inhibition of enzyme activity peak 2: CPS III, when NH4Cl is the substrate: 100% inhibition of enzyme activity peak 1: CPS II, 46% inhibition of enzyme activity peak 2: CPS III
UTP
-
inhibits activity of Escherichia coli and chimeric enzyme
UTP
P05990
slight UTP inhibition of SU(b) mutant enzyme is probably due to the chelating of Mg2+ by UTP
UTP
P07259, -
competitive, feedback inhibitor, binds to a regulatory site located in the vicinity of the carbamylphosphate synthetase catalytic subsite
MgUTP2-
-
in presence of high concentrations of dimethyl sulfoxide, MgUTP2- at low concentrations stimulates, while it is inhibitory at higher concentrations
additional information
-
not: UTP
-
additional information
-
acivicin inhibits the growth of Toxoplasma gondii
-
additional information
-
IMP binds to enzyme but the actual effect of this ligand is dependent upon temperature and assay conditions
-
additional information
-
allosteric effectors bind at domain D of eCPS
-
additional information
-
both the Luc-1b replicon and JFH1-2a virus expression inhibit CAD
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
5-phospho-alpha-D-ribose 1-diphosphate
-
activates wild-type enzyme
5-phospho-alpha-D-ribosyl 1-diphosphate
-
stimulates
5-phospho-alpha-D-ribosyl 1-diphosphate
-
stimulates
5-phospho-alpha-D-ribosyl 1-diphosphate
-
stimulates
5-phospho-alpha-D-ribosyl 1-diphosphate
-
pyrimidine-specific carbamoyl-phosphate synthase is activated, arginine-specific enzyme not
acetylornithine
-
activates
acivicin
-
selective time-dependent inhibition of L-Gln-dependent activity, L-Gln protects the enzyme from inactivation. Stimulation of NH4+-dependent activity
GTP
-
enhances activity
human Rad9 checkpoint protein
-
stimulates the carbamoyl phosphate synthetase activity of the multifunctional protein CAD. Rad9 binds to the Cpsase domain, and, moreover, this binding results in a 2fold stimulation of the CPSase activity of CAD
-
IMP
-
allosteric effector
IMP
-
His995, located in the C-terminal regulatory domain, is cross-linked with IMP
IMP
-
the effector stabilzes the (alpha,beta)4-tetramer of enzyme
IMP
-
weak activitor
IMP
-
allosteric effect on Escherichia coli enzyme in dependence of temperature, no response to chimeric enzyme
IMP
-
the nonresponsive enzyme can bind UMP at domain D and allosteric effect on chimeric enzyme
IMP
-
the IMP activator and the UMP inhibitor bind to the same site on the enzyme
ITP
-
enhances activity
L-ornithine
-
positive allosteric activation, E783, T1042, and T1043 are primarily responsible for the binding of ornithine to enzyme
L-ornithine
-
effector on ATP synthesis reaction, when ornithine is bound to the enzyme, its activation dominates the actions of UMP and IMP
L-ornithine
-
the effector stabilizes the (alpha,beta)4-tetramer of enzyme
L-ornithine
-
binds to the enzymes large subunit at the interface located between the allosteric and the carbamoyl phosphate domains
L-ornithine
-
allosteric effect on chimeric enzyme and Escherichia coli enzyme
L-ornithine
-
allosteric effect on chimeric enzyme, no effect on Saccharomyces cerevisae enzyme
N-acetyl-L-glutamate
-
-
N-acetyl-L-glutamate
-
activation of CPS III, not CPS II
N-acetyl-L-glutamate
-
only CPS III
N-acetylglutamate
-
carbamoyl-phosphate synthase II: no requirement for N-acetylglutamate
N-acetylglutamate
-
carbamoyl-phosphate synthase III: requirement for N-acetylglutamate
N-acetylglutamate
-
no requirement for N-acetyl-L-glutamate
N-acetylglutamate
-
no requirement for N-acetyl-L-glutamate
NEM
-
250fold activation of glutaminase activity. Irreversible inactivation of synthetase activity
Orn
-
allosteric activation
ornithine
-
co-substrate with carbamoyl phosphate for the second step of arginine biosynthesis, acts as a positive allosteric effector for eCPS, the catalyst for the first pathway step
phosphate
-
multifunctional proteins are phosphorylated in vivo and in vitro. This covalent modification has only a small effect on the enzymic activity, and might be a signal for protein degradation
phosphoribosyl 5'-diphosphate
-
activation of Escherichia coli and chimeric enzyme, the presence of UTP reduces the PRPP binding
thiol
-
required for Gln-dependent activity
XMP
-
enhances activity
additional information
-
activicin inhibits the Toxoplasma gondii growth
-
additional information
-
not: 5-phosphoribosyl 1-diphosphate
-
additional information
-
CPSII GATase domain as well as the C-terminal allosteric regulatory domain are essential, critical dependence on the apicomplexan CPSII GATase domain in vivo, overview
-
additional information
-
allosteric effectors bind at domain D of eCPS
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.022
-
ADP
P00968
mutant A23K, ATP-synthesis, pH 7.6, temperature not specified in the publication
0.03
-
ADP
P00968
mutant G575F, ATP-synthesis, pH 7.6, temperature not specified in the publication
0.054
-
ADP
P00968
mutant G575K, ATP-synthesis, pH 7.6, temperature not specified in the publication
0.088
-
ADP
P00968
mutant M174E, ATP-synthesis, pH 7.6, temperature not specified in the publication
0.13
-
ADP
P00968
mutant M378E, ATP-synthesis, pH 7.6, temperature not specified in the publication; wild-type, ATP-synthesis, pH 7.6, temperature not specified in the publication
0.17
-
ADP
P00968
mutant M174E/M378E, ATP-synthesis, pH 7.6, temperature not specified in the publication
0.18
-
ADP
P00968
mutant I18W/A23F/C24F, ATP-synthesis, pH 7.6, temperature not specified in the publication
0.34
-
ADP
P00968
mutant L648E, ATP-synthesis, pH 7.6, temperature not specified in the publication
0.42
-
ADP
P00968
mutant L720E, ATP-synthesis, pH 7.6, temperature not specified in the publication
0.53
-
ADP
P00968
mutant A23F, ATP-synthesis, pH 7.6, temperature not specified in the publication
2.2
-
ammonia
-
pH 7.5, 30C
111
-
ammonia
-
-
0.004
-
ATP
-
pH 7.6, 25C, HCO3(-)-dependent ATPase, mutant F755A
0.005
-
ATP
-
pH 7.6, 25C, HCO3(-)-dependent ATPase, wild-type enzyme
0.006
-
ATP
-
pH 7.6, 25C, HCO3(-)-dependent ATPase, mutant D207A
0.007
-
ATP
-
pH 7.6, 25C, HCO3(-)-dependent ATPase, mutant D753A
0.008
-
ATP
-
pH 7.6, 25C, HCO3(-)-dependent ATPase, mutant D753N
0.009
-
ATP
-
pH 7.6, 25C, HCO3(-)-dependent ATPase, mutant D207N; pH 7.6, 25C, HCO3(-)-dependent ATPase, mutant P690Q
0.013
-
ATP
P00968
mutant G575K, HCO3-dependent ATPase activity, pH 7.6, temperature not specified in the publication
0.014
-
ATP
P00968
mutant G575F, Gln-dependent ATPase activity, pH 7.6, temperature not specified in the publication; mutant G575F, HCO3-dependent ATPase activity, pH 7.6, temperature not specified in the publication
0.015
-
ATP
-
pH 7.6, 25C, Gln-dependent ATPase, mutant D207A
0.016
-
ATP
-
pH 7.6, 25C, HCO3(-)-dependent ATPase, mutant S209A
0.02
-
ATP
-
pH 7.6, 25C, Gln-dependent ATPase, mutant D207N; pH 7.6, 25C, HCO3(-)-dependent ATPase, mutant I211S
0.021
-
ATP
-
pH 7.6, 25C, HCO3(-)-dependent ATPase, mutant A144Q/D207A
0.027
-
ATP
-
pH 7.6, 25C, mutant D334A, L-glutamine hydrolysis
0.029
-
ATP
-
pH 7.6, 25C, Gln-dependent ATPase, wild-type enzyme
0.03
-
ATP
P00968
mutant M378E, HCO3-dependent ATPase activity, pH 7.6, temperature not specified in the publication
0.031
-
ATP
-
pH 7.6, 25C, Gln-dependent ATPase, mutant S209A
0.034
-
ATP
-
pH 7.6, 25C, HCO3(-)-dependent ATPase, mutant A144Q
0.038
-
ATP
-
pH 7.6, wild-type enzyme in presence of ornithine and in comparison to mutant enzymes
0.0383
-
ATP
-
pH 7.6, 25C, Gln-dependent ATPase, mutant P690Q
0.044
-
ATP
-
pH 7.6, 25C, wild-type enzyme, L-glutamine hydrolysis
0.05
-
ATP
-
glutamine-dependent ADP formation
0.051
-
ATP
P00968
wild-type, HCO3-dependent ATPase activity, pH 7.6, temperature not specified in the publication
0.052
-
ATP
-
pH 7.6, 25C, mutant Q351A, L-glutamine hydrolysis
0.06
-
ATP
-
ammonia-dependent ADP formation
0.064
-
ATP
-
pH 7.6, 25C, Gln-dependent ATPase, mutant D753A
0.067
-
ATP
-
pH 7.6, 25C, mutant Q310A, L-glutamine hydrolysis
0.07
-
ATP
P00968
mutant G575K, Gln-dependent ATPase activity, pH 7.6, temperature not specified in the publication
0.072
-
ATP
-
pH 7.6, 25C, Gln-dependent ATPase, mutant I211S
0.075
-
ATP
-
pH 7.6, 25C, mutant N311A, L-glutamine hydrolysis
0.12
-
ATP
P00968
mutant A23F, HCO3-dependent ATPase activity, pH 7.6, temperature not specified in the publication
0.121
-
ATP
-
pH 7.6, 25C, Gln-dependent ATPase, mutant D753N
0.135
-
ATP
-
pH 7.6, 25C, Gln-dependent ATPase, mutant F755A
0.154
-
ATP
-
pH 7.6, 25C, Gln-dependent ATPase, mutant A144Q/D207A
0.16
-
ATP
P00968
mutant M378E, Gln-dependent ATPase activity, pH 7.6, temperature not specified in the publication
0.21
-
ATP
P00968
mutant I18W/A23F/C24F, HCO3-dependent ATPase activity, pH 7.6, temperature not specified in the publication
0.22
-
ATP
-
mutant enzyme E306A, Gln-dependent ATP hydrolysis
0.22
-
ATP
-
pH 8.0, 37C, wild-type enzyme
0.22
-
ATP
P00968
mutant L720E, HCO3-dependent ATPase activity, pH 7.6, temperature not specified in the publication
0.24
-
ATP
P00968
wild-type, Gln-dependent ATPase activity, pH 7.6, temperature not specified in the publication
0.25
-
ATP
P00968
mutant I18W/A23F/C24F, Gln-dependent ATPase activity, pH 7.6, temperature not specified in the publication
0.26
-
ATP
P00968
mutant M911E, HCO3-dependent ATPase activity, pH 7.6, temperature not specified in the publication
0.28
-
ATP
P00968
mutant M174E/M378E, Gln-dependent ATPase activity, pH 7.6, temperature not specified in the publication
0.285
-
ATP
-
pH 7.6, 25C, Gln-dependent ATPase, mutant A144Q
0.29
-
ATP
P00968
mutant M174E/M378E, HCO3-dependent ATPase activity, pH 7.6, temperature not specified in the publication
0.32
-
ATP
-
pH 8.0, 25C, wild-type enzyme
0.33
-
ATP
P00968
mutant A23K, HCO3-dependent ATPase activity, pH 7.6, temperature not specified in the publication
0.36
-
ATP
P00968
mutant M174E, HCO3-dependent ATPase activity, pH 7.6, temperature not specified in the publication
0.37
-
ATP
-
pH 7.6, wild-type enzyme in presence of IMP and in comparison to mutant enzymes
0.38
-
ATP
P00968
mutant A23K, Gln-dependent ATPase activity, pH 7.6, temperature not specified in the publication
0.4
-
ATP
-
mutant enzyme R848A, Gln-dependent ATP hydrolysis
0.44
-
ATP
-
wild type enzyme, at 25C in 50 mM HEPES buffer, pH 7.5
0.45
-
ATP
-
pH 8.0, 25C, mutant enzyme Q262P
0.46
-
ATP
-
chimeric enzyme, in comparison to effect of phosphorylation and presence of effectors
0.47
-
ATP
-
pH 7.6, wild-type enzyme in absence of effectors and in comparison to mutant enzymes
0.5
-
ATP
P00968
mutant L648E, HCO3-dependent ATPase activity, pH 7.6, temperature not specified in the publication
0.51
-
ATP
-
mutant enzyme W437T, at 25C in 50 mM HEPES buffer, pH 7.5
0.53
-
ATP
-
deletion mutant, in comparison to the presence of effectors
0.69
-
ATP
P00968
mutant M174E, Gln-dependent ATPase activity, pH 7.6, temperature not specified in the publication
0.75
-
ATP
-
mutant enzyme W213T, at 25C in 50 mM HEPES buffer, pH 7.5
0.76
-
ATP
-
pH 8.0, 37C, mutant enzyme R675L
0.87
-
ATP
-
pH 8.0, 37C, mutant enzyme A126M
1
-
ATP
P00968
mutant M911E, Gln-dependent ATPase activity, pH 7.6, temperature not specified in the publication
1.14
-
ATP
-
pH 8.0, 37C, mutant enzyme R169H
1.2
-
ATP
P00968
mutant L648E, Gln-dependent ATPase activity, pH 7.6, temperature not specified in the publication
1.28
-
ATP
-
mutant enzyme W71T, at 25C in 50 mM HEPES buffer, pH 7.5
1.34
-
ATP
-
mutant enzyme W461T, at 25C in 50 mM HEPES buffer, pH 7.5
1.57
-
ATP
-
mutant enzyme W170T, at 25C in 50 mM HEPES buffer, pH 7.5
1.6
-
ATP
-
pH 7.6, wild-type enzyme in presence of UMP and in comparison to mutant enzymes
1.6
-
ATP
P00968
mutant A23F, Gln-dependent ATPase activity, pH 7.6, temperature not specified in the publication
1.66
-
ATP
-
pH 7.4, 37C, wild-type hybrid enzyme
1.7
-
ATP
P00968
mutant L720E, Gln-dependent ATPase activity, pH 7.6, temperature not specified in the publication
1.83
-
ATP
-
pH 7.4, 37C, mutant hybrid enzyme
1.94
-
ATP
-
mutant enzyme W175T, at 25C in 50 mM HEPES buffer, pH 7.5
2.14
-
ATP
-
-
3.02
-
ATP
-
pH 8.0, 37C, mutant enzyme V640R
8.13
-
ATP
-
pH 8.0, 37C, mutant enzyme S789P
8.36
-
ATP
-
pH 8.0, 37C, mutant enzyme P360L
0.11
-
Gln
-
mutant enzyme E916Q, Gln-dependent ATP hydrolysis
0.12
-
Gln
-
wild-type enzyme, Gln-dependent ATP hydrolysis
0.14
-
Gln
-
mutant enzyme E383QE916Q, Gln-dependent ASTP hydrolysis
0.15
-
Gln
-
mutant enzyme E383Q,Gln-dependent ATP hydrolysis
0.64
-
HCO3-
-
pH 8.0, 37C, mutant enzyme P360L
0.76
-
HCO3-
-
pH 8.0, 25C, mutant enzyme Q262P
1
-
HCO3-
-
in 30% dimethyl sulfoxide
1.2
-
HCO3-
-
HCO3-, at 8.6% dimethyl sulfoxide plus 1.4% glycerol
1.2
-
HCO3-
-
pH 7.5, 37C, value of wild-type enzyme in comparison to values of mutant enzymes
1.33
-
HCO3-
-
pH 8.0, 25C, wild-type enzyme
1.9
-
HCO3-
-
pH 8.0, 37C, wild-type enzyme
2.4
-
HCO3-
P05990
pH 7.4, 30C, Su(b) mutant
3
-
HCO3-
P05990
pH 7.4, 30C, wild-type enzyme
3.65
-
HCO3-
-
pH 8.0, 37C, mutant enzyme V640R
4.46
-
HCO3-
-
pH 8.0, 37C, mutant enzyme R675L
10
-
HCO3-
-
in 10% glycerol, pH 7
12.6
-
HCO3-
-
pH 8.0, 37C, mutant enzyme R169H
20
-
HCO3-
-
in absence of cryoprotectants
23.8
-
HCO3-
-
pH 8.0, 37C, mutant enzyme S789P
32.5
-
HCO3-
-
pH 8.0, 37C, mutant enzyme A126M
0.0119
-
L-Gln
-
-
0.021
-
L-Gln
-
in 10% glycerol, pH 7
0.027
-
L-Gln
-
in presence of 10 mM ATP plus 15 mM MgCl2
0.1
-
L-Gln
-
at 8.6% dimethyl sulfoxide plus 1.4% glycerol
0.1
-
L-Gln
P00968
mutant A23K, glutaminase activity pH 7.6, temperature not specified in the publication
0.11
-
L-Gln
-
pH 7.6, wild-type enzyme
0.14
-
L-Gln
-
at 2.0% dimethyl sulfoxide plus 8.0% glycerol
0.15
-
L-Gln
P00968
wild-type, glutaminase activity pH 7.6, temperature not specified in the publication
0.16
-
L-Gln
P00968
mutant I18W/A23F/C24F, glutaminase activity pH 7.6, temperature not specified in the publication
0.17
-
L-Gln
P00968
mutant G575K, glutaminase activity pH 7.6, temperature not specified in the publication
0.18
-
L-Gln
-
pyrimidine-specific carbamoyl-phosphate synthase
0.18
-
L-Gln
P00968
mutant L720E, glutaminase activity pH 7.6, temperature not specified in the publication; mutant M911E, glutaminase activity pH 7.6, temperature not specified in the publication
0.19
-
L-Gln
-
pH 7.6, mutant alphaD362A
0.19
-
L-Gln
P00968
mutant G575F, glutaminase activity pH 7.6, temperature not specified in the publication
0.21
-
L-Gln
P00968
mutant A23F, glutaminase activity pH 7.6, temperature not specified in the publication
0.23
-
L-Gln
P00968
mutant L648E, glutaminase activity pH 7.6, temperature not specified in the publication
0.27
-
L-Gln
-
at 2.0% dimethyl sulfoxide plus 0.3% glycerol
0.35
-
L-Gln
P00968
mutant M378E, glutaminase activity pH 7.6, temperature not specified in the publication
0.36
-
L-Gln
-
pH 7.6, mutant alphaP360A/alphaH361A
0.38
-
L-Gln
-
-
0.39
-
L-Gln
P00968
mutant M174E, glutaminase activity pH 7.6, temperature not specified in the publication
0.47
-
L-Gln
P00968
mutant M174E/M378E, glutaminase activity pH 7.6, temperature not specified in the publication
0.6
-
L-Gln
-
arginine specific carbamoyl-phosphate synthase
4.7
-
L-Gln
-
pH 7.6, mutant betaQ262A/betaR265A
7.6
-
L-Gln
-
pH 7.6, mutant betaR265A
7.8
-
L-Gln
-
pH 7.6, mutant alphaD362A/betaR265A
14.9
-
L-Gln
-
pH 7.6, mutant betaQ262A/betaR265A/betaN266A
22
-
L-Gln
-
carbamoyl-phosphate synthase belonging to the arginine pathway
0.04
-
L-glutamine
P05990
pH 7.4, 30C, Su(b) mutant
0.057
-
L-glutamine
P05990
pH 7.4, 30C, wild-type enzyme
0.111
-
L-glutamine
-
pH 7.4, 37C, mutant hybrid enzyme
0.114
-
L-glutamine
-
pH 7.4, 37C, wild-type hybrid enzyme
0.12
-
L-glutamine
-
pH 7.5, 37C, value of wild-type enzyme in comparison to values of mutant enzymes
0.13
-
L-glutamine
-
pH 7.6, 25C, wild-type enzyme, L-glutamine hydrolysis
0.15
-
L-glutamine
-
pH 7.6, 37C, L-glutamine hydrolysis
0.15
-
L-glutamine
-
pH 7.6, 25C, mutant Q351A, L-glutamine hydrolysis
0.17
-
L-glutamine
-
-
0.361
-
L-glutamine
-
chimeric enzyme, in presence of ornithine and absence of UMP
0.46
-
L-glutamine
-
pH 7.5, 30C
0.89
-
L-glutamine
-
Escherichia coli enzyme, in presence of ornithine and absence of UMP
0.91
-
L-glutamine
-
Escherichia coli enzyme, in absence of ornithine and UMP
1.075
-
L-glutamine
-
chimeric enzyme, in absence of ornithine and UMP
1.49
-
L-glutamine
-
Escherichia coli enzyme, in absence of ornithine and presence of UMP
1.86
-
L-glutamine
-
chimeric enzyme, in absence of ornithine and presence of UMP
1.99
-
L-glutamine
-
pH 7.6, 25C, mutant Q310A, L-glutamine hydrolysis
3.45
-
L-glutamine
-
pH 7.6, 25C, mutant N311A, L-glutamine hydrolysis
18.87
-
L-glutamine
-
pH 7.6, 25C, mutant D334A, L-glutamine hydrolysis
1.7
-
MgATP2-
-
at 2.0% dimethyl sulfoxide plus 0.3% glycerol or 8.0% glycerol; HCO3-, at 2.0% dimethyl sulfoxide plus 0.3% glycerol or 8.0% glycerol
9.8
-
NH4+
-
carbamoyl-phosphate synthase belonging to the pyrimidine pathway
12
-
NH4+
-
pH 7.6, mutant alphaP360A/alphaH361A/betaR265A
15
-
NH4+
-
in 10% glycerol, pH 7
24
-
NH4+
-
pH 7.6, mutant alphaD362A
26
-
NH4+
-
at 2.0% dimethyl sulfoxide plus 0.3% glycerol
26
-
NH4+
-
pH 7.6, mutant betaQ262A/betaR265A; pH 7.6, mutant betaR265A
59
-
NH4+
-
pH 7.6, mutant alphaD362A/betaR265A
110
-
NH4+
-
mutant enzyme E383Q, NH4Cl-dependent ATP hydrolysis
130
-
NH4+
-
wild-type enzyme, NH4Cl-dependent ATP hydrolysis
130
-
NH4+
-
pH 7.6, wild-type enzyme
160
-
NH4+
-
mutant enzyme E916Q, NH4Cl-dependent ATP hydrolysis
1.7
-
MgATP2-
-
MgATP2-, in 10% glycerol, pH 7
additional information
-
additional information
-
effect of cryoprotectants on the kinetic parameters
-
additional information
-
additional information
-
effect of Orn or UMP on Km-values of mutant and wild type enzyme; kinetic constants of mutant and wild type enzymes
-
additional information
-
additional information
-
kinetic constants of mutant and wild type enzymes
-
additional information
-
additional information
-
comparison of KM of partial reactions of wild-type and mutant enzymes
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
Km values for the formation of ADP, glutamate and carbonyl phosphate of the wild-type and mutant enzymes, Km values for the hydrolysis of gamma-glutamyl hydroxamate, gamma-glutamyl hydrazide, gamma-glutamyl hydroxamate and hydroxylamine of the wild-type and mutant enzymes
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
comparison of Km-values for wild-type and mutant enzymes in absence and presence of ornithine
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
kinetics of wild-type and mutant enzymes in L-glutamine-dependent and bicarbonate-dependent ATPase activities, overview
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.01
-
ADP
P00968
mutant M911E, value below 0.01, ATP-synthesis, pH 7.6, temperature not specified in the publication
0.024
-
ADP
P00968
mutant L648E, ATP-synthesis, pH 7.6, temperature not specified in the publication
0.031
-
ADP
P00968
mutant L720E, ATP-synthesis, pH 7.6, temperature not specified in the publication
0.058
-
ADP
P00968
mutant G575F, ATP-synthesis, pH 7.6, temperature not specified in the publication
0.086
-
ADP
P00968
mutant I18W/A23F/C24F, ATP-synthesis, pH 7.6, temperature not specified in the publication
0.1
-
ADP
P00968
mutant M174E, ATP-synthesis, pH 7.6, temperature not specified in the publication
0.13
-
ADP
P00968
wild-type, ATP-synthesis, pH 7.6, temperature not specified in the publication
0.15
-
ADP
P00968
mutant G575K, ATP-synthesis, pH 7.6, temperature not specified in the publication
0.2
-
ADP
P00968
mutant M378E, ATP-synthesis, pH 7.6, temperature not specified in the publication
0.22
-
ADP
P00968
mutant M174E/M378E, ATP-synthesis, pH 7.6, temperature not specified in the publication
0.23
-
ADP
P00968
mutant A23F, ATP-synthesis, pH 7.6, temperature not specified in the publication
0.32
-
ADP
P00968
mutant A23K, ATP-synthesis, pH 7.6, temperature not specified in the publication
5.1
-
ammonia
-
-
0.006
-
ATP
P00968
mutant I18W/A23F/C24F, Gln-dependent ATPase activity, pH 7.6, temperature not specified in the publication
0.01
-
ATP
P00968
mutant I18W/A23F/C24F, value below 0.01, CP-synthesis (co-substrate: L-Gln, HCO3-), pH 7.6, temperature not specified in the publication; mutant L648E,value below 0.01, CP-synthesis (co-substrate: L-Gln, HCO3-), pH 7.6, temperature not specified in the publication; mutant L720E, value below 0.01, CP-synthesis (co-substrate: L-Gln, HCO3-), pH 7.6, temperature not specified in the publication; mutant M174E/M378E, value below 0.01, CP-synthesis (co-substrate: L-Gln, HCO3-), pH 7.6, temperature not specified in the publication
0.012
-
ATP
P00968
mutant M378E, CP-synthesis (co-substrate: L-Gln, HCO3-), pH 7.6, temperature not specified in the publication
0.013
-
ATP
P00968
mutant M378E, HCO3-dependent ATPase activity, pH 7.6, temperature not specified in the publication
0.015
-
ATP
P00968
mutant M911E, value below 0.01, CP-synthesis (co-substrate: L-Gln, HCO3-), pH 7.6, temperature not specified in the publication
0.028
-
ATP
P00968
mutant M174E/M378E, HCO3-dependent ATPase activity, pH 7.6, temperature not specified in the publication
0.033
-
ATP
P00968
mutant A23F, CP-synthesis (co-substrate: L-Gln, HCO3-), pH 7.6, temperature not specified in the publication
0.035
-
ATP
P00968
mutant M378E, Gln-dependent ATPase activity, pH 7.6, temperature not specified in the publication
0.039
-
ATP
P00968
mutant I18W/A23F/C24F, HCO3-dependent ATPase activity, pH 7.6, temperature not specified in the publication
0.043
-
ATP
P00968
mutant M174E/M378E, Gln-dependent ATPase activity, pH 7.6, temperature not specified in the publication
0.053
-
ATP
P00968
mutant M174E, HCO3-dependent ATPase activity, pH 7.6, temperature not specified in the publication
0.06
-
ATP
-
pH 7.6, 25C, HCO3(-)-dependent ATPase, mutant D207N
0.07
-
ATP
-
pH 7.6, 25C, HCO3(-)-dependent ATPase, mutant F755A
0.072
-
ATP
P00968
mutant G575F, CP-synthesis (co-substrate: L-Gln, HCO3-), pH 7.6, temperature not specified in the publication
0.09
-
ATP
-
pH 7.6, 25C, HCO3(-)-dependent ATPase, mutant P690Q; pH 7.6, 25C, HCO3(-)-dependent ATPase, wild-type enzyme
0.097
-
ATP
P00968
mutant A23F, HCO3-dependent ATPase activity, pH 7.6, temperature not specified in the publication
0.1
-
ATP
-
pH 7.6, 25C, HCO3(-)-dependent ATPase, mutant A144Q
0.11
-
ATP
-
pH 7.6, 25C, HCO3(-)-dependent ATPase, mutant D207A
0.11
-
ATP
P00968
mutant M174E, Gln-dependent ATPase activity, pH 7.6, temperature not specified in the publication
0.12
-
ATP
-
pH 7.6, 25C, HCO3(-)-dependent ATPase, mutant A144Q/D207A
0.13
-
ATP
-
pH 7.6, 25C, HCO3(-)-dependent ATPase, mutant D753N
0.14
-
ATP
-
pH 7.6, 25C, HCO3(-)-dependent ATPase, mutant D753A
0.16
-
ATP
P00968
mutant A23K, CP-synthesis (co-substrate: L-Gln, HCO3-), pH 7.6, temperature not specified in the publication
0.17
-
ATP
P00968
mutant A23K, HCO3-dependent ATPase activity, pH 7.6, temperature not specified in the publication; wild-type, HCO3-dependent ATPase activity, pH 7.6, temperature not specified in the publication
0.18
-
ATP
P00968
mutant G575K, HCO3-dependent ATPase activity, pH 7.6, temperature not specified in the publication
0.19
-
ATP
P00968
mutant G575F, HCO3-dependent ATPase activity, pH 7.6, temperature not specified in the publication
0.28
-
ATP
P00968
mutant A23K, Gln-dependent ATPase activity, pH 7.6, temperature not specified in the publication
0.29
-
ATP
-
pH 7.6, 25C, HCO3(-)-dependent ATPase, mutant I211S
0.33
-
ATP
P00968
mutant M911E, HCO3-dependent ATPase activity, pH 7.6, temperature not specified in the publication
0.35
-
ATP
-
pH 7.6, 25C, HCO3(-)-dependent ATPase, mutant S209A
0.39
-
ATP
P00968
mutant L720E, HCO3-dependent ATPase activity, pH 7.6, temperature not specified in the publication
0.5
-
ATP
P00968
mutant M911E, Gln-dependent ATPase activity, pH 7.6, temperature not specified in the publication
0.59
-
ATP
P00968
mutant L648E, HCO3-dependent ATPase activity, pH 7.6, temperature not specified in the publication
0.78
-
ATP
-
-
1.3
-
ATP
P00968
mutant A23F, Gln-dependent ATPase activity, pH 7.6, temperature not specified in the publication
1.33
-
ATP
-
pH 7.6, 25C, mutant D334A, L-glutamine hydrolysis
1.51
-
ATP
-
pH 7.6, 25C, Gln-dependent ATPase, mutant D207A
1.65
-
ATP
-
pH 7.6, 25C, Gln-dependent ATPase, mutant D207N
1.7
-
ATP
-
pH 7.6, 25C, Gln-dependent ATPase, mutant A144Q/D207A
1.71
-
ATP
-
pH 7.6, 25C, Gln-dependent ATPase, mutant D753A
1.9
-
ATP
P00968
mutant G575K, CP-synthesis (co-substrate: L-Gln, HCO3-), pH 7.6, temperature not specified in the publication; mutant M174E, CP-synthesis (co-substrate: L-Gln, HCO3-), pH 7.6, temperature not specified in the publication; wild-type, CP-synthesis (co-substrate: L-Gln, HCO3-), pH 7.6, temperature not specified in the publication
2
-
ATP
P00968
mutant L720E, Gln-dependent ATPase activity, pH 7.6, temperature not specified in the publication
2.13
-
ATP
-
pH 7.6, 25C, mutant N311A, L-glutamine hydrolysis
2.2
-
ATP
-
ammonia-dependent ADP formation
2.43
-
ATP
-
pH 7.6, 25C, Gln-dependent ATPase, mutant S209A
3.19
-
ATP
-
pH 7.6, 25C, mutant Q351A, L-glutamine hydrolysis
3.2
-
ATP
P00968
mutant L648E, Gln-dependent ATPase activity, pH 7.6, temperature not specified in the publication
3.3
-
ATP
P00968
mutant G575F, Gln-dependent ATPase activity, pH 7.6, temperature not specified in the publication; mutant G575K, Gln-dependent ATPase activity, pH 7.6, temperature not specified in the publication
3.35
-
ATP
-
chimeric enzyme, in comparison to effect of phosphorylation and presence of effectors
3.6
-
ATP
P00968
wild-type, Gln-dependent ATPase activity, pH 7.6, temperature not specified in the publication
3.94
-
ATP
-
pH 7.6, 25C, Gln-dependent ATPase, mutant A144Q
4.04
-
ATP
-
pH 7.6, 25C, Gln-dependent ATPase, wild-type enzyme
4.77
-
ATP
-
pH 7.6, 25C, Gln-dependent ATPase, mutant I211S
4.79
-
ATP
-
pH 7.6, 25C, wild-type enzyme, L-glutamine hydrolysis
5.18
-
ATP
-
pH 7.6, 25C, Gln-dependent ATPase, mutant F755A
5.3
-
ATP
-
deletion mutant, in comparison to the presence of effectors
5.6
-
ATP
-
pH 7.6, 25C, Gln-dependent ATPase, mutant D753N
5.75
-
ATP
-
pH 7.6, 25C, mutant Q310A, L-glutamine hydrolysis
6.08
-
ATP
-
-
6.8
-
ATP
-
glutamine-dependent ADP formation
9.01
-
ATP
-
pH 7.6, 25C, Gln-dependent ATPase, mutant P690Q
164
-
ATP
-
pH 7.4, 37C, mutant hybrid enzyme
2500
-
ATP
-
pH 7.4, 37C, wild-type hybrid enzyme
0.1
-
Gln
-
mutant enzyme E306A, Gln-dependent ATP hydrolysis
0.15
-
Gln
-
mutant enzyme E25Q/E383Q/E604Q, Gln-dependent ATP hydrolysis
0.17
-
Gln
-
mutant enzyme E577Q, Gln-dependent ATP hydrolysis
0.32
-
Gln
-
mutant enzyme E25Q/E383Q, Gln-dependent ATP hydrolysis
0.95
-
Gln
-
mutant enzyme R848A, Gln-dependent ATP hydrolysis
1.5
-
Gln
-
mutant enzyme E604Q, Gln-dependent ATP hydrolysis
3.2
-
Gln
-
mutant enzyme E383Q,Gln-dependent ATP hydrolysis
4
-
Gln
-
mutant enzyme E383QE916Q, Gln-dependent ATP hydrolysis; wild-type enzyme, Gln-dependent ATP hydrolysis
4.2
-
Gln
-
mutant enzyme E916Q, Gln-dependent ATP hydrolysis
0.005
-
L-Gln
-
pH 7.6, mutant alphaP360A/alphaH361A/betaR265A
0.1
-
L-Gln
P00968
mutant M174E/M378E, glutaminase activity pH 7.6, temperature not specified in the publication
0.13
-
L-Gln
P00968
mutant I18W/A23F/C24F, glutaminase activity pH 7.6, temperature not specified in the publication; mutant M378E, glutaminase activity pH 7.6, temperature not specified in the publication
0.14
-
L-Gln
P00968
mutant M911E, glutaminase activity pH 7.6, temperature not specified in the publication
0.15
-
L-Gln
P00968
mutant M174E, glutaminase activity pH 7.6, temperature not specified in the publication
0.21
-
L-Gln
P00968
mutant A23K, glutaminase activity pH 7.6, temperature not specified in the publication
0.84
-
L-Gln
P00968
mutant L720E, glutaminase activity pH 7.6, temperature not specified in the publication
0.88
-
L-Gln
-
pH 7.6, mutant betaQ262A/betaR265A/betaN266A
1
-
L-Gln
-
pH 7.6, mutant betaQ262A/betaR265A
1.08
-
L-Gln
P00968
mutant A23F, glutaminase activity pH 7.6, temperature not specified in the publication
1.1
-
L-Gln
-
pH 7.6, mutant betaR265A
1.2
-
L-Gln
-
pH 7.6, mutant alphaD362A/betaR265A
1.3
-
L-Gln
P00968
mutant L648E, glutaminase activity pH 7.6, temperature not specified in the publication
1.4
-
L-Gln
-
pH 7.6, wild-type enzyme
2.2
-
L-Gln
P00968
wild-type, glutaminase activity pH 7.6, temperature not specified in the publication
2.3
-
L-Gln
-
pH 7.6, mutant alphaP360A/alphaH361A
2.4
-
L-Gln
-
pH 7.6, mutant alphaD362A
3
-
L-Gln
P00968
mutant G575F, glutaminase activity pH 7.6, temperature not specified in the publication
3.1
-
L-Gln
P00968
mutant G575K, glutaminase activity pH 7.6, temperature not specified in the publication
0.53
-
L-glutamine
-
pH 7.6, 25C, mutant Q351A, L-glutamine hydrolysis
1.05
-
L-glutamine
-
pH 7.6, 25C, mutant N311A, L-glutamine hydrolysis
1.17
-
L-glutamine
-
pH 7.6, 25C, mutant D334A, L-glutamine hydrolysis
1.6
-
L-glutamine
-
pH 7.6, 25C, mutant Q310A, L-glutamine hydrolysis
2.13
-
L-glutamine
-
pH 7.6, 25C, wild-type enzyme, L-glutamine hydrolysis
9.4
-
L-glutamine
-
-
193
-
L-glutamine
-
pH 7.4, 37C, mutant hybrid enzyme
0.097
-
NH4+
-
mutant enzyme E25Q/E383Q/E604Q, NH4Cl-dependent ATP hydrolysis
0.12
-
NH4+
-
mutant enzyme E577Q, NH4Cl-dependent ATP hydrolysis
0.51
-
NH4+
-
mutant enzyme E25Q/E383Q, NH4Cl-dependent ATP hydrolysis
1.3
-
NH4+
-
mutant enzyme E604Q, NH4Cl-depebndent ATP hydrolysis; mutant enzyme E916Q, NH4Cl-dependent ATP hydrolysis
1.7
-
NH4+
-
mutant enzyme E383Q, NH4Cl-dependent ATP hydrolysis
1.9
-
NH4+
-
pH 7.6, wild-type enzyme
2
-
NH4+
-
pH 7.6, mutant alphaP360A/alphaH361A
2.5
-
NH4+
-
pH 7.6, mutant alphaP360A/alphaH361A/betaR265A; pH 7.6, mutant betaR265A
3.6
-
NH4+
-
pH 7.6, mutant betaQ262A/betaR265A
3.8
-
NH4+
-
pH 7.6, mutant alphaD362A
3.9
-
NH4+
-
wild-type enzyme, NH4Cl-dependent ATP hydrolysis
5.8
-
NH4+
-
pH 7.6, mutant alphaD362A/betaR265A
2660
-
L-glutamine
-
pH 7.4, 37C, wild-type hybrid enzyme
additional information
-
additional information
-
comparison of kcat in absence and presence of L-ornithine, UMP and IMP for wild-type and mutant enzymes
-
additional information
-
additional information
-
comparison of kcat of partial reactions of wild-type and mutant enzymes
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
kcat values for the formation of ADP, glutamate and carbonyl phosphate of the wild-type and mutant enzymes, kcat values for the hydrolysis of gamma-glutamyl hydroxamate, gamma-glutamyl hydrazide, gamma-glutamyl hydroxamate and hydroxylamine of the wild-type and mutant enzymes
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
comparison of kcat-values for wild-type and mutant enzymes in absence and presence of ornithine
-
additional information
-
additional information
-
-
-
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0018
-
UMP
-
pH 8.0, 37C, wild-type enzyme in comparison to mutant enzymes
0.004
-
UMP
-
pH 8.0, 24C
0.005
-
UMP
-
pH 7.5, 37C, value of wild-type enzyme in comparison to values of mutant enzymes
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.00035
-
Q8RSS4 and Q8RSS3
mutant starin S36K
0.00095
-
-
-
0.001125
-
Q8RSS4 and Q8RSS3
wild-type strain
0.041
-
-
recombinant enzyme
0.348
-
-
recombinant mutant P909C/G919C
0.472
-
-
recombinant mutant P909C
0.524
-
-
recombinant mutant G919C
0.855
-
-
recombinant wild-type enzyme
additional information
-
-
-
additional information
-
-
-
additional information
-
-
the catalytic activity is dependent on the presence or absence of specific allosteric ligands but independent of the oligomeric state of the protein
additional information
-
-
constant specific activity of wild-type enzyme irrespective of the enzyme concentration or of the elution position of the enzyme in the gel filtration system under conditions at which different oligomeric forms predominate
additional information
-
P05990
-
additional information
-
-
-
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
4.2
-
-
and a second optimum at pH 9.5, glutaminase activity
4.2
-
-
wild-type enzyme
6.6
-
-
mutant enzyme E841K
6.7
-
-
highest activity in the pH-range 6.7-8.8
6.8
7.2
-
Gln-dependent activity
7.5
-
-
with either 5 mM Gln or 100 mM NH4+ as substrate
7.6
-
-
assay at
7.8
-
-
NH4+-dependent activity
8
-
-
triethanolamine buffer
9.3
-
-
wild-type enzyme
9.5
-
-
and a second optimum at pH 4.2, glutaminase activity
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.7
8.5
-
6.7: highest activity in the pH-range 6.7-8.5, pH 7.2: 95% of the activity at pH 6.7, pH 8.5: 64% of the activity at pH 6.7
7.5
8.5
-
7.5: about 65% of maximal activity, 8.5: about 40% of maximal activity
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
25
37
-
assay at
25
-
-
assay at
37
-
-
assay at
70
80
-
CPS.A-CPS.B complex
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
B2G3Q3
growth medium is bovine milk
Manually annotated by BRENDA team
-
mammary carcinoma DMBA-1C, DMBA-5A, 205A, R3230AC, RNC-211
Manually annotated by BRENDA team
-
about 10fold higher activity than in normal liver
Manually annotated by BRENDA team
-
maintained in human foreskin fibroblasts
Manually annotated by BRENDA team
additional information
-
rapidly growing tissues, e.g. fetal liver, spleen, and testis have much more carbamoyl-phosphate synthase activity than other tissues testes, e.g. lung, uterus, heart, brain and muscle. Tumors are more active than most normal tissues
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
carbamoyl-phosphate-synthase/aspartate-transcarbamoylase complex
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
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)
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
116200
-
O50302
the large subunit
120000
-
-
chimeric protein
160000
170000
-
gel filtration, CPS III
163000
-
-
sedimentation equilibrium ultracentrifugation
168000
-
-
sucrose density gradient ultracentrifugation
171000
-
-
-
additional information
-
-
the multienzyme complex of carbamoyl-phosphate synthase(glutamine), aspartate carbamoyltransferase and dihydroorotase has a MW of 870000 as determined by sedimentation equilibrium studies and 210000 by SDS-PAGE
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
the large catalytic subunit has a MW of 130000, SDS-PAGE
?
-
x * 56000 (subunit N) + x * 71000 (subunit C), SDS-PAGE
?
-
x * 40000 + x * 118000
dimer
-
1 * 40000, subunit contains the binding site for glutamine, + 1 * 133000, subunit contains the binding sites for NH4+, HCO3-, ATP, and the allosteric effectors. The light and heavy subunits are encoded by the genetically linked car A and car B genes, respectively
dimer
-
1 * 40000 + 1 * 130000, SDS-PAGE
dimer
-
1 * 44000 + 1 * 12200, SDS-PAGE
dimer
-
1 * 45000, beta, + 1 * 110000, alpha
dimer
-
000 + 1 * 118000, carbamoyl-phosphate synthase belonging to the pyrimidine pathway, SDS-PAGE
dimer
-
1 * 40000, glutaminase subunit, + 1 * 120000, synthase subunit. The synthase subunit consists of two homologous domains, CPS.A and CPS.B, which catalyze the two different ATP-dependent partial reactions involved in carbamoyl-phosphate synthesis
dimer
-
at low concentrations in presence of UMP
dimer
-
The enzyme consists of an amidotransferase domain or subunit, GLN, 40000 Da, that hydrolyzes glutamine and transfers the ammonia to the synthetase component, CPS, 120000 Da, where the biosynthetic reaction occurs. The CPS domain is composed of two homologous subdomains, CPS.A and CPS.B, that catalyse different ATP-dependent reactions involved in the carbamoyl phosphate synthesis. The CPS.A and CPS.B monomers could each catalyse all of the partial reactions, but catalysis of the overall synthesis of carbamoyl phosphate requires a dimer composed of two of the equivalent domains.
dimer
-
2 * 58000, SDS-PAGE, chimeric protein
dimer
-
1 * 41400 + 1 * 117700, the large subunit catalyses the carbamoyl phosphate synthesis from ammonia in three steps, and binds the effectors in its 15000 domain
dimer
Escherichia coli L814
-
1 * 41400 + 1 * 117700, the large subunit catalyses the carbamoyl phosphate synthesis from ammonia in three steps, and binds the effectors in its 15000 domain
-
heterodimer
-
the small subunit belongs to the class I amidotransferase family of enzymes, the reaction mechanism of the small subunit proceeds through the formation of the glutamyl thioester intermediate
heterodimer
-
alpha,beta, 1 * 42000 + 1 * 118000
heterodimer
-
1 * 42000 + 1 * 118000
heterodimer
-
alpha,beta, 1 * 42000 + 1 * 118000, the effectors ornithine, IMP and UMP modulate the oligomerization of the heterodimer to higher ordered species
heterodimer
-
alpha,beta, 1 * 42000 + 1 * 118000, the ammonia tunnel is responsible for the migration of ammonia, that is produced at the active site of the small subunit and migrates to the large subunit, the carbamate tunnel connects the two active sites contained within the carboxy phosphate and carbamoyl phosphate domains of the large subunit
heterodimer
-
alpha,beta, that readily converts to an tetrameric species: 4 * alpha, beta in presence of positive allosteric effectors, the smaller of two subunits contains 382 amino acid residues and is responsible for the hydrolysis of free ammonia, the larger subunit contains 1073 amino acid residues and provides the binding sites for the two MgATP2 molecules required for the assembly of carbamoyl phosphate, structure and reaction mechanism
heterodimer
-
alpha,beta, the small subunit is able to catalyze the hydrolysis of glutamine, the large subunit catalyses the formation of carbamoyl phosphate using ammonia as a nitrogen source
heterodimer
-
alpha,beta, the heteodimer aggregates to form tetramers of dimers, structure
heterodimer
-
alpha,beta, that readly coverts to an tetrameric species: 4 * alpha, beta in presence of positive allosteric effectors
heterodimer
-
-
heterodimer
-
small and large subunit, the small subunit contains a class I (trpG)-type glutaminase domain to hydrolyze glutamine to ammonia. carB is composed of three exons encoding a 120 kDa large subunit, consisting of the duplicated synthetase regions and the ATP-binding domains to synthesize carbamoyl phosphate
heterodimer
-
1 * 42000, small subunit, + 118000, large subunit
octamer
-
4 * 42000 + 4 * 118000
tetramer
-
at high concentrations in presence of ornithine
heterotrimer
-
CPS.A-subunit, CPS.B-subunit and glutaminase-subunit, 1* 64000 Da, 1 * 63000 Da and 1 * 45000 Da, but only the CPS.A-CPS.B-dimer has catalytic activity, SDS-PAGE
additional information
-
enzyme can exist in different monomer conformations and states of association
additional information
-
-
additional information
-
reversible concentration-dependent self-association. When the enzyme concentration is lower than 0.01 g/L the enzyme exists as monomer under all conditions
additional information
-
enzyme exists in monomer, dimer, and higher oligomeric forms, which are associated with its regulation by allosteric effectors. In barbital buffer the enzyme is present as a monomer. In sodium phosphate buffer, the enzyme exists as a partially dissociating dimer. In presence of phosphate and a positive allosteric effector, the maximum association state of the enzyme is a tetramer. UMP promotes conversion to a dimer
additional information
-
self-association does not play a role in regulation of enzyme activity
additional information
-
NH4+ or Orn promotes oligomer formation. Tetramer or higher oligomeric species in potassium phosphate buffer containing Orn
additional information
-
the homologous CPS.A. and CPS.B. subdomains are functionally equivalent, although in the native enzyme they may have different functions resulting from their juxtaposition relative to the other components in the complex
additional information
-
in absence of effectors the enzyme behaves as a dissociating system possibly reflecting the dimer-tetramer equilibrium
additional information
-
the enzyme consists of two polypeptide chains referred to as small and large subunits, which contain a total of three separate active sites that are connected by an intramolecular tunnel
additional information
-
the smaller subunit contains the binding site for the hydrolysis of glutamine, whereas the large subunit catalyzes the formation of carbamoyl phosphate. The enzyme posssesses three distinct active sites and an ammonia tunnel, that starts at the active site in the small subunit and leads to the active site in the N-terminal domain of the large subunit
additional information
-
crystal structure modelling and analysis, A2 is the glutamine amidotransferase domain and A1 is involved in communicating active site occupancy between the amidotransferase and synthetase active sites. Domains B and C are regions of internal duplication andeach contains an ATP grasp fold. Domains D' and D contain the interfaces for eCPS self-association. In addition to this role, domain D is the site for allosteric regulation of eCPS. The intramolecular tunnel connecting the three active sites
additional information
-
presence of three spatially distinct active sites that are linked by two long molecular tunnels that extend approximately 100 A from one end of the protein to the other
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
side-chain modification
-
construction of a chimeric enzyme consisting of Escherichia coli subdomains A1 and A2 fused to the mammalian enzyme subdomain B3
side-chain modification
-
construction of a chimeric enzyme, in which the C-terminal 136 residues of Escherichia coli enzyme are replaced by the corresponding residues of Saccharomyces cerevisae enzyme
side-chain modification
-
formation of a hybrid complex consisting of the mammalian glutaminase domain and the isolated Escherichia coli carbamoyl-phosphate synthetase domains, the steady state kinetic parameters of the hybrid are similar to those obtained for carbamoyl-phosphate synthase-aspartate carbamoyltransferase-dihydroorotase
side-chain modification
-
construction of a chimeric enzyme, in which the C-terminal 136 residues of Escherichia coli enzyme are replaced by the corresponding residues of Saccharomyces cerevisae enzyme
side-chain modification
Saccharomyces cerevisiae LPL26
-
construction of a chimeric enzyme, in which the C-terminal 136 residues of Escherichia coli enzyme are replaced by the corresponding residues of Saccharomyces cerevisae enzyme
-
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
C248D mutant of small subunit, crystals are grown at 4C by batch from 8% poly(ethylene glycol) 8000, 0.65 M tetraethylammonium chloride, 0.5 mM MnCl2, 100 mM KCl, 1.5 mM ADP, 25 mM GEPES, pH 7.4, 0.5 mM L-Orn. The crystals belong to the space group P2(1)2(1)2(1) with unit cell dimensions of a = 151.1 A, b = 164.2 A, and c = 331.5A and one complete (alphabeta)4-heeterotetramer per asymmetric unit
-
in presence of both IMP and ornithine, structural analysis of the nucleotide monophosphate allosteric binding site for enzyme
-
molecular dynamics simulation. Carbamate, the product of the reaction involving ATP, bicarbonate, and ammonia, must be delivered from the site of formation to the site of utilization by traveling nearly 40 A within the enzyme. The tunnel is composed of three continuous water pockets and two narrow connecting parts, near residues A23 and G575. The two narrow parts render two free energy barriers of 6.7 and 8.4 kcal/mol, respectively. Three water pockets are filled with about 21, 9, and 9 waters, respectively, and the corresponding relative free energies of carbamate residing in these free energy minima are 5.8, 0, and 1.6 kcal/mol, respectively. The release of phosphate into solution at the site for the formation of carbamate allows the side chain of R306 to rotate toward E25, E383, and E604. This rotation is virtually prohibited by a barrier of at least 23 kcal/mol when phosphate remains bound. This conformational change not only opens the entrance of the tunnel but also shields the charge-charge repulsion from the three glutamate residues when carbamate passes through the tunnel
P00968
the structure of enzyme cocrystallized in the presence of the 5-adenylylimidodiphosphate, is determined to 2.1 A by X-ray crystallographic analysis, the three active sites of enzyme communicate via domain movements, the first example of such a domain movement is described
-
the three active sites within the alpha,beta heterodimer are separated by a linear distance of nearly 100 A and are interconnected by two molecular tunnels
-
X-ray crystallographic analysis, the three active sites on the protein are widely separated from one another
-
X-ray crystallographic structure
-
pH STABILITY
pH STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7
-
-
half-life: 20 min
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
25
80
-
The activity of the CPS.A-CPS.B complex remains unchanged between 25-60 C and then increases 54% at 70C. The loss of catalytic activity above 80C is indicated of thermal denaturation. The large increase in thermal stability at temperatures prior to thermal denaturation is not observed in the CPS.A-CPS.B-glutaminase-subunit complex.
37
-
-
15 min, stable in absence of dimetyl sulfoxide and glycerol
additional information
-
-
the thermal stability of cloned enzyme is identical regardless of the growth temperature of Bacillus stearothermophilus between 42C and 63C. The thermal stability of the cloned enzyme is not affected by expression at 37C in Bacillus subtilis or E. coli
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
treatment with 1 M potassium thiocyanate results in reversible dissociation into its subunits which retain catalytic activity
-
enzyme is most stable in the presence of 30% dimethyl sulfoxide, 5% glycerol, 1 mM dithiothreitol. MgATP2-, MgUTP2-, and 5-phospho-alpha-D-ribosyl 1-diphosphate effectively stabilize
-
OXIDATION STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
Gln-dependent function of carbamoyl-phosphate synthase is inactivated by incubating the enzyme in air with low concentrations of dithiothreitol, glutathione, Cys, homocysteine, or 2-mercaptoethanol
-
1731
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-80C, stable, 6 months
-
-80C, 30% dimethyl sulfoxide, 5% glycerol, 1 mM dithiothreitol, stable for 6 months
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
recombinant enzyme
-
recombinant wild-type and mutant enzymes
-
native enzyme partially
-
Escherichia coli and chimeric enzyme
-
recombinant mutant enzymes from Escherichia coli strain RC50 to over 95% purity
-
recombinant wild-type and mutant enzymes
-
Sephacryl S-300 gel filtration and Resource-Q column chromatography
-
wild-type and mutant enzyme
-
-
Q8RSS4 and Q8RSS3
multifunctional protein bearing carbamoyl-phosphate synthase, aspartate transcarbamoylase, and dihydroorotase activities
-
multienzyme complex of carbamoyl-phosphate synthase(glutamine), aspartate carbamoyltransferase and dihydroorotase
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expression in Escherichia coli
-
cloning of car B wild-type and mutant enzymes
-
Escherichia coli and chimeric enzyme are expressed in Escherichia coli L673
-
expressed in Escherichia coli
P00968
expression in Echerichia coli
-
expression in Escherichia coli
-
expression of mutant enzymes in Escherichia coli strain RC50
-
expression of wild-type and mutant enzymes
-
expression of wild-type and mutant enzymes in Escherichia coli strain L673
-
the plasmids containing the carAB genes are transformed in the RC50 cell line of Escherichia coli for expression of the wild-type and mutant forms of CPS
-
carbamoyl-phosphate synthase belonging to the pyrimidine pathway
-
pyrAb encodes the large subunit
O50302
cloning and characterization of the carAB genes
Q8RSS4 and Q8RSS3
multifunctional protein, that catalyzes the first three steps in de novo pyrimidine biosynthesis, expression in Escherichia coli
-
the two subdomains CPS.A. and CPS.B.
-
subcloning of each of the subunits into the pET-28b vector, expression in Escherichia coli
-
expression in Saccharomyces pombe
-
gene carB, DNA and amino acid sequence determination and analysis
B2G3Q3
construction and expression of a functional minigene of CPSII for functional complementation of mutants, overview
-
structure and organization of enzyme gene
-
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
carB expression is partly downregulated by ammonium treatment, while carA expression is unaffected
-
accumulation of CPSase gene transcripts is highly reduced following seedling incubation with uridine; accumulation of CPSase gene transcripts is highly reduced following seedling incubation with uridine
B9V284, -
mRNA levels of MtCPSs1 and MtCPSs2 are significantly increased after supplying plants with ornithine alone or in combination with uridine or arginine compared to plants treated with only uridine or arginine, respectively; mRNA levels of MtCPSs1 and MtCPSs2 are significantly increased after supplying plants with ornithine alone or in combination with uridine or arginine compared to plants treated with only uridine or arginine, respectively
B9V284, -
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
K954E
-
enzyme activity in absence of effectors is slightly lower when compared with the enzyme from wild-type. UTP inhibition is reduced
A126M
-
mutation in large subunit significantly decreases synthesis of carbamoyl phosphate without completely inactivating the enzyme
A144Q
-
mutant enzyme retains ATP specificity
A182V
-
reduced apparent affinity for HCO3-, sensitivity toward UMP is unchanched in comparison to wild-type enzyme
A182V/S948F
-
mutant is insensitive towards pyrimidine and purine nucleosides, activation by ornithine, although the affinity for this ligand is fivefold reduced in comparison to wild-type enzyme
A23F
P00968
migration of carbamate through the narrowest part of the carbamate tunnel is blocked. From the kinetic data the only reaction significantly affected by this mutation is the overall synthesis of carbamoyl phosphate (only 1.7% compared to wild-type); mutant designed to block the migration of carbamate through the narrowest parts of the carbamate tunnel. Mutant retains 1.7% of the catalytic activity for the synthesis of carbamoyl phosphate relative to the wild type CPS
A23K
P00968
A23K mutation decreases the glutamine-dependent ATPase activity by an order of magnitude. While there is a decrease in the rate of carbamoyl phosphate formation, the enzyme utilizes two molecules of ATP for every molecule of carbamoyl phosphate synthesized
A251C
-
site-directed mutagenesis in the ammonia tunnel, analysis of secondary structure by circular dichroism measurements
A309C
-
kinetic properties are similar to those of the wild-type enzyme
A309C/S35C
-
kinetic properties are similar to those of the wild-type enzyme
A309S
-
kinetic properties are similar to those of the wild-type enzyme
A311L
-
site-directed mutagenesis in the ammonia tunnel, analysis of secondary structure by circular dichroism measurements
A314C
-
site-directed mutagenesis in the ammonia tunnel, analysis of secondary structure by circular dichroism measurements
C232G/A251G/A314G
-
site-directed mutagenesis in the ammonia tunnel, analysis of secondary structure by circular dichroism measurements
C232V/A251V/A314V
-
site-directed mutagenesis in the ammonia tunnel, analysis of secondary structure by circular dichroism measurements
C248D
-
partial glutaminase activity of the mutant protein is increased 40fold relative to the wild-type enzyme
C269G
-
Cys269Gly and Cys269Ser mutants bind significant amounts of Gln but do not hydrolyze Gln. The mutants are able to catalyze carbamoyl-phosphate formation with NH4+ as nitrogen donor, at a rate equal to that of the wild type enzyme. The mutant enzyme catalyzes ATP synthesis from ADP and carbamoyl phosphate at the usual rates. Substantial increase in bicarbonate-dependent ATPase
C269S
-
Cys269Gly and Cys269Ser mutants bind significant amounts of Gln but do not hydrolyze Gln. The mutants are able to catalyze carbamoyl-phosphate formation with NH4+ as nitrogen donor, at a rate equal to that of the wild type enzyme. The mutant enzyme catalyzes ATP synthesis from ADP and carbamoyl phosphate at the usual rates. Substantial increase in bicarbonate-dependent ATPase
C269S
-
mutant is unable to hydrolyse glutamine, the mutant is proved to be an adequate mimic for studies of the Michaelis complex
D207A
-
mutations of the residues E215A, N283A, E299Q, N301D, and R303Q result in proteins which are unable to synthesize carbamoyl phosphate at a significant rate. The binding of bicarbonate is most affected by the mutagenesis of residues E215A, E299Q, N301D, and R303Q. The Km for ATP is most affected in the mutant enzymes R129A, R169A, Q285A, and N301D. No significant changes in the catalytic constants are observed in the mutants R82A and D207A. All of the mutations, with the exception of the N301D mutant, primarily effect the enzyme by altering the step for the phosphorylation of bicarbonate. Mutation N301D also disrupts the catalytic step involved in the phosphorylation of carbamate
D207A
-
mutant enzyme retains ATP specificity
D207N
-
mutant enzyme retains ATP specificity
D334A
-
site-directed mutagenesis, the mutation has essentially no effect on the Km for L-glutamine
D362A
-
mutation in alpha subunit, 2fold increase in turnover number for NH4+, 5.4fold decrease in KM-value for NH4+, 1.7fold increase in turnover number for Gln, 1.7fold increase in KM-value for Gln
D362A/betaR265A
-
mutation S362A in alpha-subunit, mutation R265A in beta-subunit,3fold increase in turnover number for NH4+, 2.2fold decrease in KM-value for NH4+, 1.2fold decrease in turnover number for Gln, 71fold increase in KM-value for Gln
D753A
-
mutant enzyme retains ATP specificity
D753N
-
mutant enzyme retains ATP specificity
D753X
-
residues within the carbamate domain of the large subunit of CPS are selected as targets for mutagenesis. Mutant enzymes E761A, E841Q, N843D, R845Q have diminished ability to synthesize carbamoyl phosphate. Mutant enzymes R715A, Q829A, and R675A show elevated Michaelis constants for MgATP2- in the partial back reaction. The mutant enzymes E761A, N827A, E841Q, N843D, and R845Q show significant increases in the Michaelis constant for either bicarbonate or carbamoyl phosphate. No significant alterations are noted upon mutation of either R571 or D753
DELTA119
-
truncation mutant DELTA14, with a removal of 14 amino acids at the carboxy terminus of the large subunit shows a 40fold decrease in Gln-dependent ATPase activity. Similar losses in activity are observed for the DELTA50, DELTA65, DELTA91, and DELTA119 mutant proteins. However formation of carbamoyl phosphate is detected even after the deletion of 119 amino acids from the carboxy-terminal end of the large subunit. No allosteric effects are observed in the presence of Orn even after the removal of the last 119 amino acids from the large subunit of CPS. Mutant enzymes G921V and G921I are unstable and are defective for the synthesis of carbamoyl phosphate. The T977A mutant is not regulated by UMP, but the full allosteric effect is observed with Orn. The R1030A and R1031A mutants enzymes exhibit wild type properties, mutant G921A shows no alteration in any of the allosteric properties. Mutant N1015A cannot be purified
DELTA14
-
truncation mutant DELTA14, with a removal of 14 amino acids at the carboxy terminus of the large subunit shows a 40fold decrease in Gln-dependent ATPase activity. Similar losses in activity are observed for the DELTA50, DELTA65, DELTA91, and DELTA119 mutant proteins. However formation of carbamoyl phosphate is detected even after the deletion of 119 amino acids from the carboxy-terminal end of the large subunit. No allosteric effects are observed in the presence of Orn even after the removal of the last 119 amino acids from the large subunit of CPS. Mutant enzymes G921V and G921I are unstable and are defective for the synthesis of carbamoyl phosphate. The T977A mutant is not regulated by UMP, but the full allosteric effect is observed with Orn. The R1030A and R1031A mutants enzymes exhibit wild type properties, mutant G921A shows no alteration in any of the allosteric properties. Mutant N1015A cannot be purified
DELTA50
-
truncation mutant DELTA14, with a removal of 14 amino acids at the carboxy terminus of the large subunit shows a 40fold decrease in Gln-dependent ATPase activity. Similar losses in activity are observed for the DELTA50, DELTA65, DELTA91, and DELTA119 mutant proteins. However formation of carbamoyl phosphate is detected even after the deletion of 119 amino acids from the carboxy-terminal end of the large subunit. No allosteric effects are observed in the presence of Orn even after the removal of the last 119 amino acids from the large subunit of CPS. Mutant enzymes G921V and G921I are unstable and are defective for the synthesis of carbamoyl phosphate. The T977A mutant is not regulated by UMP, but the full allosteric effect is observed with Orn. The R1030A and R1031A mutants enzymes exhibit wild type properties, mutant G921A shows no alteration in any of the allosteric properties. Mutant N1015A cannot be purified
DELTA65
-
truncation mutant DELTA14, with a removal of 14 amino acids at the carboxy terminus of the large subunit shows a 40fold decrease in Gln-dependent ATPase activity. Similar losses in activity are observed for the DELTA50, DELTA65, DELTA91, and DELTA119 mutant proteins. However formation of carbamoyl phosphate is detected even after the deletion of 119 amino acids from the carboxy-terminal end of the large subunit. No allosteric effects are observed in the presence of Orn even after the removal of the last 119 amino acids from the large subunit of CPS. Mutant enzymes G921V and G921I are unstable and are defective for the synthesis of carbamoyl phosphate. The T977A mutant is not regulated by UMP, but the full allosteric effect is observed with Orn. The R1030A and R1031A mutants enzymes exhibit wild type properties, mutant G921A shows no alteration in any of the allosteric properties. Mutant N1015A cannot be purified
DELTA91
-
truncation mutant DELTA14, with a removal of 14 amino acids at the carboxy terminus of the large subunit shows a 40fold decrease in Gln-dependent ATPase activity. Similar losses in activity are observed for the DELTA50, DELTA65, DELTA91, and DELTA119 mutant proteins. However formation of carbamoyl phosphate is detected even after the deletion of 119 amino acids from the carboxy-terminal end of the large subunit. No allosteric effects are observed in the presence of Orn even after the removal of the last 119 amino acids from the large subunit of CPS. Mutant enzymes G921V and G921I are unstable and are defective for the synthesis of carbamoyl phosphate. The T977A mutant is not regulated by UMP, but the full allosteric effect is observed with Orn. The R1030A and R1031A mutants enzymes exhibit wild type properties, mutant G921A shows no alteration in any of the allosteric properties. Mutant N1015A cannot be purified
E215A
-
mutations of the residues E215A, N283A, E299Q, N301D, and R303Q result in proteins which are unable to synthesize carbamoyl phosphate at a significant rate. The binding of bicarbonate is most affected by the mutagenesis of residues E215A, E299Q, N301D, and R303Q. The Km for ATP is most affected in the mutant enzymes R129A, R169A, Q285A, and N301D. No significant changes in the catalytic constants are observed in the mutants R82A and D207A. All of the mutations, with the exception of the N301D mutant, primarily effect the enzyme by altering the step for the phosphorylation of bicarbonate. Mutation N301D also disrupts the catalytic step involved in the phosphorylation of carbamate
E25Q/E383Q
-
46.7fold decreased turnover number for carbamoyl-phosphate synthesis
E25Q/E383Q/E604Q
-
more than 700fold decreased turnover number for carbamoyl-phosphate synthesis
E299Q
-
mutations of the residues E215A, N283A, E299Q, N301D, and R303Q result in proteins which are unable to synthesize carbamoyl phosphate at a significant rate. The binding of bicarbonate is most affected by the mutagenesis of residues E215A, E299Q, N301D, and R303Q. The Km for ATP is most affected in the mutant enzymes R129A, R169A, Q285A, and N301D. No significant changes in the catalytic constants are observed in the mutants R82A and D207A. All of the mutations, with the exception of the N301D mutant, primarily effect the enzyme by altering the step for the phosphorylation of bicarbonate. Mutation N301D also disrupts the catalytic step involved in the phosphorylation of carbamate
E383Q
-
1.1fold decreased turnover number for carbamoyl-phosphate synthesis
E383Q/E916Q
-
3.9fold decreased turnover number for carbamoyl-phosphate synthesis
E577Q
-
437.5fold decreased turnover number for carbamoyl-phosphate synthesis
E604Q
-
3.7fold decreased turnover number for carbamoyl-phosphate synthesis
E761A
-
residues within the carbamate domain of the large subunit of CPS are selected as targets for mutagenesis. Mutant enzymes E761A, E841Q, N843D, R845Q have diminished ability to synthesize carbamoyl phosphate. Mutant enzymes R715A, Q829A, and R675A show elevated Michaelis constants for MgATP2- in the partial back reaction. The mutant enzymes E761A, N827A, E841Q, N843D, and R845Q show significant increases in the Michaelis constant for either bicarbonate or carbamoyl phosphate. No significant alterations are noted upon mutation of either R571 or D753
E761A
-
the residue is a key in the allosteric signal transduction pathway from ornithine to ATP
E783A
-
the allosteric activation of enzyme by ornithine is completely suppressed
E783K
-
the allosteric activation of enzyme by ornithine is completely suppressed
E841K
-
comparison of 15N-isotope effects in mutant and wild-type enzyme on the hydrolysis of glutamine, the rate of glutamine hydrolysis in the mutant is not affected by MgATP2 and HCO3-, with the wild-type enzyme in the absence of MgATP2 and HCO3- the isotope effect id reduced
E841Q
-
residues within the carbamate domain of the large subunit of CPS are selected as targets for mutagenesis. Mutant enzymes E761A, E841Q, N843D, R845Q have diminished ability to synthesize carbamoyl phosphate. Mutant enzymes R715A, Q829A, and R675A show elevated Michaelis constants for MgATP2- in the partial back reaction. The mutant enzymes E761A, N827A, E841Q, N843D, and R845Q show significant increases in the Michaelis constant for either bicarbonate or carbamoyl phosphate. No significant alterations are noted upon mutation of either R571 or D753
E892A
-
the allosteric activation of enzyme by ornithine is completely suppressed
E892K
-
the allosteric activation of enzyme by ornithine is completely suppressed
E916Q
-
6.7fold decreased turnover number for carbamoyl-phosphate synthesis
F755A
-
mutant enzyme retains ATP specificity
G1008A
-
mutation abolishs IMP activation and UMP inhibition in comparison to wild-type enzyme
G293A
-
kinetic properties are similar to those of the wild-type enzyme
G293I
-
kinetic properties are similar to those of the wild-type enzyme
G293S
-
kinetic properties are similar to those of the wild-type enzyme
G359F
-
glutaminase and bicarbonate-dependent ATPase reaction are uncoupled from one another, the mutant enzyme is fully functional when external ammonia is utilized as the nitrogen source but is unable to use glutamine for the synthesis of carbamoyl phosphate
G359F
-
Km values of L-glutamine are increased
G359L
-
Km values of L-glutamine are increased
G359S
-
Km values of L-glutamine are increased
G359Y
-
glutaminase and bicarbonate-dependent ATPase reaction are uncoupled from one another, the mutant enzyme is fully functional when external ammonia is utilized as the nitrogen source but is unable to use glutamine for the synthesis of carbamoyl phosphate
G575F
P00968
mutant designed to block the migration of carbamate through the narrowest parts of the carbamate tunnel. Mutant retains 3.8% of the catalytic activity for the synthesis of carbamoyl phosphate relative to the wild type CPS; mutation to G575 does not exhibit significant pertubations to the kinetic constants of the partial reactions, G575F mutant has a 50fold reduction in the rate of carbamoyl phosphate formation (attributed to the restricted passage of carbamate through the tunnel). The insertion of a larger phenylalanine side chain is anticipated to create a more efficient blockage of the tunnel. Of the mutants made in the carbamate tunnel, G575F is the most efficacious at blocking the passage of carbamate without disrupting any of the active sites
G575K
P00968
mutation to G575 does not exhibit significant pertubations to the kinetic constants of the partial reactions, mutant has similar catalytic properties as the wild-type protein, suggesting that the conformational change of Arg-848 may not be crucial for the transport of carbamate
G824D
-
strongly reduced affinity for ornithine in comparison to wild-type enzyme
G919C
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
G921A
-
truncation mutant DELTA14, with a removal of 14 amino acids at the carboxy terminus of the large subunit shows a 40fold decrease in Gln-dependent ATPase activity. Similar losses in activity are observed for the DELTA50, DELTA65, DELTA91, and DELTA119 mutant proteins. However formation of carbamoyl phosphate is detected even after the deletion of 119 amino acids from the carboxy-terminal end of the large subunit. No allosteric effects are observed in the presence of Orn even after the removal of the last 119 amino acids from the large subunit of CPS. Mutant enzymes G921V and G921I are unstable and are defective for the synthesis of carbamoyl phosphate. The T977A mutant is not regulated by UMP, but the full allosteric effect is observed with Orn. The R1030A and R1031A mutants enzymes exhibit wild type properties, mutant G921A shows no alteration in any of the allosteric properties. Mutant N1015A cannot be purified
G921I
-
truncation mutant DELTA14, with a removal of 14 amino acids at the carboxy terminus of the large subunit shows a 40fold decrease in Gln-dependent ATPase activity. Similar losses in activity are observed for the DELTA50, DELTA65, DELTA91, and DELTA119 mutant proteins. However formation of carbamoyl phosphate is detected even after the deletion of 119 amino acids from the carboxy-terminal end of the large subunit. No allosteric effects are observed in the presence of Orn even after the removal of the last 119 amino acids from the large subunit of CPS. Mutant enzymes G921V and G921I are unstable and are defective for the synthesis of carbamoyl phosphate. The T977A mutant is not regulated by UMP, but the full allosteric effect is observed with Orn. The R1030A and R1031A mutants enzymes exhibit wild type properties, mutant G921A shows no alteration in any of the allosteric properties. Mutant N1015A cannot be purified
G921V
-
truncation mutant DELTA14, with a removal of 14 amino acids at the carboxy terminus of the large subunit shows a 40fold decrease in Gln-dependent ATPase activity. Similar losses in activity are observed for the DELTA50, DELTA65, DELTA91, and DELTA119 mutant proteins. However formation of carbamoyl phosphate is detected even after the deletion of 119 amino acids from the carboxy-terminal end of the large subunit. No allosteric effects are observed in the presence of Orn even after the removal of the last 119 amino acids from the large subunit of CPS. Mutant enzymes G921V and G921I are unstable and are defective for the synthesis of carbamoyl phosphate. The T977A mutant is not regulated by UMP, but the full allosteric effect is observed with Orn. The R1030A and R1031A mutants enzymes exhibit wild type properties, mutant G921A shows no alteration in any of the allosteric properties. Mutant N1015A cannot be purified
G997A
-
mutation abolishs IMP activation and UMP inhibition in comparison to wild-type enzyme
H975L
-
mutation abolishes oligomer formation even high enzyme concentrations or in the presence of ornithine
H975L/N987V
-
mutation abolishes oligomer formation even high enzyme concentrations or in the presence of ornithine
H995A
-
mutant exhibits normal kinetics for the activator ornithine and for the substrates in presence of ornithine, the mutation selectiviely decrease 5.6 and 2.3fold the apparent affinity for UMP and IMP, mutation abolishes the ability to be photoaffinity labeled with IMP
H995A
-
mutation has little effect on enzyme activity in comparison to wild-type enzyme
I18W/A23F/C24F
P00968
triple mutant I18W/A23F/C24F is made to disrupt the water pocket that may facilitate the passage of carbamate through the carbamate tunnel. This mutant significantly hinders the overall rate of carbamoyl phosphate synthesis and it diminishes all of the other partial reactions
I211S
-
mutant enzyme retains ATP specificity
I352F
-
site-directed mutagenesis in the ammonia tunnel, analysis of secondary structure by circular dichroism measurements
K1061A
-
mutation abolishs IMP activation and UMP inhibition in comparison to wild-type enzyme
K954A
-
mutation has little effect on enzyme activity in comparison to wild-type enzyme
K993A
-
mutation reduces enzyme activity in comparison to wild-type enzyme
K993W
-
mutation has little effect on enzyme activity in comparison to wild-type enzyme
K993W/H995A
-
mutation abolishs IMP activation and UMP inhibition in comparison to wild-type enzyme
L270K
-
ammonia-dependent carbamoyl phosphate synthesis activity is very similar to that of the wild-type enzyme, L-glutamine-dependent carbamoyl phosphate synthesis activity is 5fold decreased in comparison to the wild-type enzyme, the glutamine binding is almost entirely abolished
L421E
-
mutant forms a (alpha/beta)2-dimer in presence of ornithine, IMP and UMP
L421E
-
mutation prevents tetramer but not dimer formation
L421E/H975L/N987V
-
mutation abolishes oligomer formation even high enzyme concentrations or in the presence of ornithine
L421E/N987D
-
no oligomerization
L648E
P00968
mutant shows no detectable rate of carbamoyl phosphate formation. Little effect on the rates of all partial reactions is observed. Thus the reactions at the small subunit and the carboxy phosphate active sites remains unperturbed. The L648E mutant exhibits a 10fold drop in the rate of the glutaminase reaction which is due to the uncoupling between the carboxy phosphate and glutaminase active sites
L720E
P00968
the rates for both the glutamine- and HCO3--dependent ATPase reactions are largely unaffected by the mutation. The rate of the partial ATP-synthesis reaction is decreased 4fold. These perturbations may be due to an altered active site environment which diminishes the rate ADP phosphorylation by carbamoyl phosphate. No carbamoyl phosphate formation is detected. Mutant can structurally block the exit of the carbamate tunnel although the presence of the glutamate also weakens the assistance of Arg-848 during the synthesis of carbamoyl phosphate
L990A
-
mutation abolishes oligomer formation even high enzyme concentrations or in the presence of ornithine
L990A
-
mutation abolishs IMP activation and UMP inhibition in comparison to wild-type enzyme
M174E
P00968
mutant has significant reductions in the rates of the ATPase and carbamoyl phosphate synthesis reactions. Mutation does not affect the rate of the partial ATP synthesis reaction
M174E/M378E
P00968
catalytic properties of the double mutant, M174E/M378E, are similar to the single mutants with regard to the various partial reactions. Double mutant is unable to synthesize carbamoyl phosphate
M378E
P00968
mutant has significant reductions in the rates of the ATPase and carbamoyl phosphate synthesis reactions. Mutation does not affect the rate of the partial ATP synthesis reaction
N1015A
-
truncation mutant DELTA14, with a removal of 14 amino acids at the carboxy terminus of the large subunit shows a 40fold decrease in Gln-dependent ATPase activity. Similar losses in activity are observed for the DELTA50, DELTA65, DELTA91, and DELTA119 mutant proteins. However formation of carbamoyl phosphate is detected even after the deletion of 119 amino acids from the carboxy-terminal end of the large subunit. No allosteric effects are observed in the presence of Orn even after the removal of the last 119 amino acids from the large subunit of CPS. Mutant enzymes G921V and G921I are unstable and are defective for the synthesis of carbamoyl phosphate. The T977A mutant is not regulated by UMP, but the full allosteric effect is observed with Orn. The R1030A and R1031A mutants enzymes exhibit wild type properties, mutant G921A shows no alteration in any of the allosteric properties. Mutant N1015A cannot be purified
N283A
-
mutations of the residues E215A, N283A, E299Q, N301D, and R303Q result in proteins which are unable to synthesize carbamoyl phosphate at a significant rate. The binding of bicarbonate is most affected by the mutagenesis of residues E215A, E299Q, N301D, and R303Q. The Km for ATP is most affected in the mutant enzymes R129A, R169A, Q285A, and N301D. No significant changes in the catalytic constants are observed in the mutants R82A and D207A. All of the mutations, with the exception of the N301D mutant, primarily effect the enzyme by altering the step for the phosphorylation of bicarbonate. Mutation N301D also disrupts the catalytic step involved in the phosphorylation of carbamate
N301D
-
mutations of the residues E215A, N283A, E299Q, N301D, and R303Q result in proteins which are unable to synthesize carbamoyl phosphate at a significant rate. The binding of bicarbonate is most affected by the mutagenesis of residues E215A, E299Q, N301D, and R303Q. The Km for ATP is most affected in the mutant enzymes R129A, R169A, Q285A, and N301D. No significant changes in the catalytic constants are observed in the mutants R82A and D207A. All of the mutations, with the exception of the N301D mutant, primarily effect the enzyme by altering the step for the phosphorylation of bicarbonate. Mutation N301D also disrupts the catalytic step involved in the phosphorylation of carbamate
N301K
-
mutation in large subunit significantly decreases synthesis of carbamoyl phosphate without completely inactivating the enzyme
N311A
-
site-directed mutagenesis, the mutant shows increased Km for L-glutamine compared to the wild-type enzyme
N827A
-
residues within the carbamate domain of the large subunit of CPS are selected as targets for mutagenesis. Mutant enzymes E761A, E841Q, N843D, R845Q have diminished ability to synthesize carbamoyl phosphate. Mutant enzymes R715A, Q829A, and R675A show elevated Michaelis constants for MgATP2- in the partial back reaction. The mutant enzymes E761A, N827A, E841Q, N843D, and R845Q show significant increases in the Michaelis constant for either bicarbonate or carbamoyl phosphate. No significant alterations are noted upon mutation of either R571 or D753
N843Q
-
residues within the carbamate domain of the large subunit of CPS are selected as targets for mutagenesis. Mutant enzymes E761A, E841Q, N843D, R845Q have diminished ability to synthesize carbamoyl phosphate. Mutant enzymes R715A, Q829A, and R675A show elevated Michaelis constants for MgATP2- in the partial back reaction. The mutant enzymes E761A, N827A, E841Q, N843D, and R845Q show significant increases in the Michaelis constant for either bicarbonate or carbamoyl phosphate. No significant alterations are noted upon mutation of either R571 or D753
N987D
-
mutant forms a (alpha/beta)-monomer regardless of the presence of any allosteric effectors
N987V
-
mutation decreases the oligomerisation
N992A
-
mutation abolishes oligomer formation even high enzyme concentrations or in the presence of ornithine
P165S
-
reduced apparent affinity for HCO3-, sensitivity toward UMP is increased in comparison to wild-type enzyme
P170L
-
reduced apparent affinity for HCO3-, sensitivity toward UMP is increased in comparison to wild-type enzyme
P360A/H361A
-
mutation in beta-subunit, turnover number for NH4+ is nearly identical to wild-type value, 1.6fold increase in turnover number for Gln, 3.2fold increase in KM-value for Gln
P360A/H361A/R265A
-
mutations P360A and H361A in alpha-subunit, mutation R265A in beta-subunit, mutant enzyme is unable to utilize glutamine for the synthesis of carbamoyl phosphate1.3fold increase in turnover number for NH4+, 11.8fold decrease in KM-value for NH4+
P360L
-
UMP still inhibits the activity of the mutant enzyme, 30fold reduced affinity for ornithine and 20fold reduced affinity for IMP in comparison to wild-type enzyme
P360L
-
mutation in large subunit significantly decreases synthesis of carbamoyl phosphate without completely inactivating the enzyme
P690Q
-
mutant enzyme retains ATP specificity
P909C
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
P909C/G919C
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
Q262A/R265A
-
mutation in beta-subunit 1.9fold increase in turnover number for NH4+, 5fold decrease in KM-value for NH4+, 1.4fold decrease in turnover number for Gln, 43fold increase in KM-value for Gln
Q262A/R265A/N266A
-
mutation in beta-subunit, 1.6fold decrease in turnover number for Gln, 13.5fold increase in KM-value for Gln
Q262P
-
mutation causes marked enzyme instability, mutation in large subunit significantly decreases synthesis of carbamoyl phosphate without completely inactivating the enzyme
Q273E
-
ammonia-dependent carbamoyl phosphate synthesis activity is very similar to that of the wild-type enzyme, L-glutamine-dependent carbamoyl phosphate synthesis activity is equivalent to the wild-type enzyme, but the mutant is 10fold impaired in its L-glutamine binding ability in comparison to wild-type enzyme
Q273E/L270K
-
ammonia-dependent carbamoyl phosphate synthesis activity is very similar to that of the wild-type enzyme, L-glutamine-dependent carbamoyl phosphate synthesis activity is 25fold decreased in comparison to the wild-type enzyme, the glutamine binding is almost entirely abolished
Q273E/N240S
-
ammonia-dependent carbamoyl phosphate synthesis activity is very similar to that of the wild-type enzyme, L-glutamine-dependent carbamoyl phosphate synthesis activity is equivalent to the wild-type enzyme
Q285A
-
mutations of the residues E215A, N283A, E299Q, N301D, and R303Q result in proteins which are unable to synthesize carbamoyl phosphate at a significant rate. The binding of bicarbonate is most affected by the mutagenesis of residues E215A, E299Q, N301D, and R303Q. The Km for ATP is most affected in the mutant enzymes R129A, R169A, Q285A, and N301D. No significant changes in the catalytic constants are observed in the mutants R82A and D207A. All of the mutations, with the exception of the N301D mutant, primarily effect the enzyme by altering the step for the phosphorylation of bicarbonate. Mutation N301D also disrupts the catalytic step involved in the phosphorylation of carbamate
Q310A
-
site-directed mutagenesis, the mutant shows increased Km for L-glutamine compared to the wild-type enzyme
Q351A
-
site-directed mutagenesis, the mutant shows highly increased Km for L-glutamine compared to the wild-type enzyme
Q829A
-
residues within the carbamate domain of the large subunit of CPS are selected as targets for mutagenesis. Mutant enzymes E761A, E841Q, N843D, R845Q have diminished ability to synthesize carbamoyl phosphate. Mutant enzymes R715A, Q829A, and R675A show elevated Michaelis constants for MgATP2- in the partial back reaction. The mutant enzymes E761A, N827A, E841Q, N843D, and R845Q show significant increases in the Michaelis constant for either bicarbonate or carbamoyl phosphate. No significant alterations are noted upon mutation of either R571 or D753
R1020A
-
mutation has little effect on enzyme activity in comparison to wild-type enzyme
R1021A
-
mutation has little effect on enzyme activity in comparison to wild-type enzyme
R1030A
-
truncation mutant DELTA14, with a removal of 14 amino acids at the carboxy terminus of the large subunit shows a 40fold decrease in Gln-dependent ATPase activity. Similar losses in activity are observed for the DELTA50, DELTA65, DELTA91, and DELTA119 mutant proteins. However formation of carbamoyl phosphate is detected even after the deletion of 119 amino acids from the carboxy-terminal end of the large subunit. No allosteric effects are observed in the presence of Orn even after the removal of the last 119 amino acids from the large subunit of CPS. Mutant enzymes G921V and G921I are unstable and are defective for the synthesis of carbamoyl phosphate. The T977A mutant is not regulated by UMP, but the full allosteric effect is observed with Orn. The R1030A and R1031A mutants enzymes exhibit wild type properties, mutant G921A shows no alteration in any of the allosteric properties. Mutant N1015A cannot be purified
R1031A
-
truncation mutant DELTA14, with a removal of 14 amino acids at the carboxy terminus of the large subunit shows a 40fold decrease in Gln-dependent ATPase activity. Similar losses in activity are observed for the DELTA50, DELTA65, DELTA91, and DELTA119 mutant proteins. However formation of carbamoyl phosphate is detected even after the deletion of 119 amino acids from the carboxy-terminal end of the large subunit. No allosteric effects are observed in the presence of Orn even after the removal of the last 119 amino acids from the large subunit of CPS. Mutant enzymes G921V and G921I are unstable and are defective for the synthesis of carbamoyl phosphate. The T977A mutant is not regulated by UMP, but the full allosteric effect is observed with Orn. The R1030A and R1031A mutants enzymes exhibit wild type properties, mutant G921A shows no alteration in any of the allosteric properties. Mutant N1015A cannot be purified
R129A
-
mutations of the residues E215A, N283A, E299Q, N301D, and R303Q result in proteins which are unable to synthesize carbamoyl phosphate at a significant rate. The binding of bicarbonate is most affected by the mutagenesis of residues E215A, E299Q, N301D, and R303Q. The Km for ATP is most affected in the mutant enzymes R129A, R169A, Q285A, and N301D. No significant changes in the catalytic constants are observed in the mutants R82A and D207A. All of the mutations, with the exception of the N301D mutant, primarily effect the enzyme by altering the step for the phosphorylation of bicarbonate. Mutation N301D also disrupts the catalytic step involved in the phosphorylation of carbamate
R169A
-
mutations of the residues E215A, N283A, E299Q, N301D, and R303Q result in proteins which are unable to synthesize carbamoyl phosphate at a significant rate. The binding of bicarbonate is most affected by the mutagenesis of residues E215A, E299Q, N301D, and R303Q. The Km for ATP is most affected in the mutant enzymes R129A, R169A, Q285A, and N301D. No significant changes in the catalytic constants are observed in the mutants R82A and D207A. All of the mutations, with the exception of the N301D mutant, primarily effect the enzyme by altering the step for the phosphorylation of bicarbonate. Mutation N301D also disrupts the catalytic step involved in the phosphorylation of carbamate
R169H
-
mutation in large subunit significantly decreases synthesis of carbamoyl phosphate without completely inactivating the enzyme
R265A
-
mutation in beta-subunit, 1.3fold increase in turnover number for NH4+, 5fold decrease in KM-value for NH4+, 1.3fold decrease in turnover number for Gln, 69fold increase in KM-value for Gln
R303Q
-
mutations of the residues E215A, N283A, E299Q, N301D, and R303Q result in proteins which are unable to synthesize carbamoyl phosphate at a significant rate. The binding of bicarbonate is most affected by the mutagenesis of residues E215A, E299Q, N301D, and R303Q. The Km for ATP is most affected in the mutant enzymes R129A, R169A, Q285A, and N301D. No significant changes in the catalytic constants are observed in the mutants R82A and D207A. All of the mutations, with the exception of the N301D mutant, primarily effect the enzyme by altering the step for the phosphorylation of bicarbonate. Mutation N301D also disrupts the catalytic step involved in the phosphorylation of carbamate
R306A
-
more than 700fold decreased turnover number for carbamoyl-phosphate synthesis
R571X
-
residues within the carbamate domain of the large subunit of CPS are selected as targets for mutagenesis. Mutant enzymes E761A, E841Q, N843D, R845Q have diminished ability to synthesize carbamoyl phosphate. Mutant enzymes R715A, Q829A, and R675A show elevated Michaelis constants for MgATP2- in the partial back reaction. The mutant enzymes E761A, N827A, E841Q, N843D, and R845Q show significant increases in the Michaelis constant for either bicarbonate or carbamoyl phosphate. No significant alterations are noted upon mutation of either R571 or D753
R675A
-
residues within the carbamate domain of the large subunit of CPS are selected as targets for mutagenesis. Mutant enzymes E761A, E841Q, N843D, R845Q have diminished ability to synthesize carbamoyl phosphate. Mutant enzymes R715A, Q829A, and R675A show elevated Michaelis constants for MgATP2- in the partial back reaction. The mutant enzymes E761A, N827A, E841Q, N843D, and R845Q show significant increases in the Michaelis constant for either bicarbonate or carbamoyl phosphate. No significant alterations are noted upon mutation of either R571 or D753
R675L
-
mutation in large subunit significantly decreases synthesis of carbamoyl phosphate without completely inactivating the enzyme
R715A
-
residues within the carbamate domain of the large subunit of CPS are selected as targets for mutagenesis. Mutant enzymes E761A, E841Q, N843D, R845Q have diminished ability to synthesize carbamoyl phosphate. Mutant enzymes R715A, Q829A, and R675A show elevated Michaelis constants for MgATP2- in the partial back reaction. The mutant enzymes E761A, N827A, E841Q, N843D, and R845Q show significant increases in the Michaelis constant for either bicarbonate or carbamoyl phosphate. No significant alterations are noted upon mutation of either R571 or D753
R82A
-
mutations of the residues E215A, N283A, E299Q, N301D, and R303Q result in proteins which are unable to synthesize carbamoyl phosphate at a significant rate. The binding of bicarbonate is most affected by the mutagenesis of residues E215A, E299Q, N301D, and R303Q. The Km for ATP is most affected in the mutant enzymes R129A, R169A, Q285A, and N301D. No significant changes in the catalytic constants are observed in the mutants R82A and D207A. All of the mutations, with the exception of the N301D mutant, primarily effect the enzyme by altering the step for the phosphorylation of bicarbonate. Mutation N301D also disrupts the catalytic step involved in the phosphorylation of carbamate
R845Q
-
residues within the carbamate domain of the large subunit of CPS are selected as targets for mutagenesis. Mutant enzymes E761A, E841Q, N843D, R845Q have diminished ability to synthesize carbamoyl phosphate. Mutant enzymes R715A, Q829A, and R675A show elevated Michaelis constants for MgATP2- in the partial back reaction. The mutant enzymes E761A, N827A, E841Q, N843D, and R845Q show significant increases in the Michaelis constant for either bicarbonate or carbamoyl phosphate. No significant alterations are noted upon mutation of either R571 or D753
R848A
-
233fold decreased turnover number for carbamoyl-phosphate synthesis
S209A
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mutant enzyme retains ATP specificity
S35C
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kinetic properties are similar to those of the wild-type enzyme
S35F
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kinetic properties are similar to the wild-type enzyme, only KM-value of L-glutamine is 5fold increased
S35Y
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site-directed mutagenesis in the ammonia tunnel, analysis of secondary structure by circular dichroism measurements
S743N
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minor modification of kinetic parameters in comparison to wild-type enzyme
S743N/G824D
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strongly reduced affinity for ornithine in comparison to wild-type enzyme
S789P
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mutation in large subunit significantly decreases synthesis of carbamoyl phosphate without completely inactivating the enzyme
S948A
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mutation has little effect on enzyme activity in comparison to wild-type enzyme
S948F
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mutant enzyme is unsensitive to UMP and IMP, but is still activated by ornithine, although to a reduced extent
T1042I
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greatly reduced activation by ornithine, the affinities for both UMP and IMP are reduced in comparison to wild-type enzyme in comparison to wild-type enzyme; mutation reduces activation by ornithine, the mutated enzyme is still sensitive to UMP and IMP
T1042K
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the residue is responsible for the binding of ornithine to enzyme
T1043K
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the allosteric activation of enzyme by ornithine is completely suppressed
T249V
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site-directed mutagenesis in the ammonia tunnel, analysis of secondary structure by circular dichroism measurements
T800F
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reduced affinity for ornithine, increased sensitivity for UMP in comparison to wild-type enzyme
T974A
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mutation abolishs IMP activation and UMP inhibition in comparison to wild-type enzyme
T977A
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truncation mutant DELTA14, with a removal of 14 amino acids at the carboxy terminus of the large subunit shows a 40fold decrease in Gln-dependent ATPase activity. Similar losses in activity are observed for the DELTA50, DELTA65, DELTA91, and DELTA119 mutant proteins. However formation of carbamoyl phosphate is detected even after the deletion of 119 amino acids from the carboxy-terminal end of the large subunit. No allosteric effects are observed in the presence of Orn even after the removal of the last 119 amino acids from the large subunit of CPS. Mutant enzymes G921V and G921I are unstable and are defective for the synthesis of carbamoyl phosphate. The T977A mutant is not regulated by UMP, but the full allosteric effect is observed with Orn. The R1030A and R1031A mutants enzymes exhibit wild type properties, mutant G921A shows no alteration in any of the allosteric properties. Mutant N1015A cannot be purified
V640R
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mutation in large subunit significantly decreases synthesis of carbamoyl phosphate without completely inactivating the enzyme
V991A
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mutation has little effect on enzyme activity in comparison to wild-type enzyme
V994A
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mutation reduces enzyme activity in comparison to wild-type enzyme
W170T
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increased Km compared to the wild type enzyme
W175T
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increased Km compared to the wild type enzyme
W213T
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increased Km compared to the wild type enzyme
W437T
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increased Km compared to the wild type enzyme
W461T
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increased Km compared to the wild type enzyme
W71T
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increased Km compared to the wild type enzyme
K954A
Escherichia coli L814
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mutation has little effect on enzyme activity in comparison to wild-type enzyme
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K993A
Escherichia coli L814
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mutation reduces enzyme activity in comparison to wild-type enzyme
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S948A
Escherichia coli L814
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mutation has little effect on enzyme activity in comparison to wild-type enzyme
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V991A
Escherichia coli L814
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mutation has little effect on enzyme activity in comparison to wild-type enzyme
-
S44A
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mutant of hybrid enzyme shows km value similar to the wild-type hybrid, the kcat values of glutamine and ATP are 14fold lower in comparison to wild-type hybrid, the functional linkage that coordinates the reactions on the glutaminase and carbamoyl-phosphate synthetase domains is lost as a result of mutation
D1220Y
P07259, -
aspartate transcarbamylase activity of the multifunctional mutant protein carbamylphosphate synthetase/aspartate transcarbamylase is no longer inhibited by UTP, carbamylphosphate synthetase activity retains fully sensitive to this effector
N1094D
P07259, -
aspartate transcarbamylase activity of the multifunctional mutant protein carbamylphosphate synthetase/aspartate transcarbamylase is no longer inhibited by UTP, carbamylphosphate synthetase activity retains fully sensitive to this effector
R1076S
P07259, -
aspartate transcarbamylase activity of the multifunctional mutant protein carbamylphosphate synthetase/aspartate transcarbamylase is no longer inhibited by UTP, carbamylphosphate synthetase activity retains fully sensitive to this effector
Y1096C
P07259, -
aspartate transcarbamylase activity of the multifunctional mutant protein carbamylphosphate synthetase/aspartate transcarbamylase is no longer inhibited by UTP, carbamylphosphate synthetase activity retains fully sensitive to this effector
N348A
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site-directed mutagenesis, the mutation reduces complementation activity, GATase activity and the initial growth rate, but the N348A mutant exhibits the high virulence phenotype of the parental RH strain in C57Bl/6 mice
N348R
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site-directed mutagenesis, the mutation completely abolishes complementation activity and GATase activity
additional information
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construction of carB mutants lacking a functional large subunit. The carB mutant shows negligible effects on overall arginine levels. The levels of ornithine, citrulline and arginine remain low in the mutant. the ammonium level of carB mutant cells are similar to the wild-type in air, overview
S974A
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under conditions of saturating Utp (2 mM), mutant enzyme shows similar degree of inhibition as wild-type enzyme. Activation by 5-phosphoribosyl-alpha-pyrophosphate is completely abolished at 0.05 mM, a concentration where near maximal activation is observed with wild-type enzyme
additional information
P05990
supressor of black mutation, Su(b), which causes a loss of UTP feedback inhibition, is a missense mutation resulting in a glutamate to lysine substitution within the second ATP binding site of enzyme
M911E
P00968
the rate for both the glutamine- and HCO3--dependent ATPase reactions are largely unaffected by the mutation. The rate of the partial ATP-synthesis reaction is virtually undetectable. This perturbation may be due to an altered active site environment which diminishes the rate ADP phosphorylation by carbamoyl phosphate. Only limited carbamoyl phosphate formation is detected with mutant M911E. M911E mutant can structurally block the exit of the carbamate tunnel although the presence of glutamate also weakens the assistance of Arg-848 during the synthesis of carbamoyl phosphate
additional information
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smaller recombinant proteins in which the subdomains A1, A2, A3, B1, B2, or B3 of the synthetase subunit are deleted, show that subdomains A1 and B1 are attenuation domains which suppress the intrinsically high activity and are required for the physical association with the glutaminase subunit
additional information
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the 120000 MW synthetase subunit and the 40000 MW glutaminase subunit, in which the intergenic region between the contiguous carA and carB genes is deleted and the sequence encoding the carbamoyl-phosphate synthase subunits is fused in frame. The resulting fusion protein is activated 10fold relative to the native protein, it is responsive to the allosteric activator Orn, and cannot use NH4+ as a nitrogen donor. The functional linkage that coordinates the rate of glutamine hydrolysis with the activation of bicarbonate is abolished
additional information
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several mutations increase, reduce, suppresse, or reverse the allosteric effects of ornithine, UMP and IMP, the mutational analysis of ornithine, and potassium binding site strongly supports the proposal for a coupling between the allosteric transduction signal pathways for UMP,IMP and ornithine
additional information
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A series of mutants created and probes the direct transport of carbamate through the carbamate tunnel, the partial reactions of enzyme have not been significantly impaired by these mutations, and thus, the catalytic machinery at the individual active site has not been functionally pertured
additional information
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a chimeric deletion mutant A1A2B3 lacks 59 of 163 residues from the carboxyl end of the Escherichia coli /mammalian chimera, this mutant is somewhat more active than the full-length chimeric protein but has reduced sensitivity to allosteric effectors
additional information
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A series of mutants created within the ammonia tunnel are prepared by placement of a constriction via site-directed mutagenesis. The degree of constriction within the ammonia tunnel of these enzymes is found to correlate to the extent of the uncoupling of the partial reactions, the diminution of carbamoyl phosphate formation, and the percentage of the internally derived ammonia that is channelled through the ammonia tunnel
additional information
-
the mutants are constructed to mimic the potentially significant substitutions which is observed in the frog enzyme and to allow determination of the effects of these changes on the glutamine binding ability of enzyme
V994A
Escherichia coli L814
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mutation reduces enzyme activity in comparison to wild-type enzyme
-
additional information
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downregulation of CAD, i.e. carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase, by specific siRNA
additional information
-
the 29-amino acid linker, which connects the glutaminase domain and the synthetase domain is deleted. The deletion mutant catalyzes glutamine-dependent carbamoyl phosphate synthesis, but is activated 10fold relative to its wild type counterpart. NH4+-dependent synthesis of carbamoyl phosphate is abolished. The mutant enzyme is still sensitive to inhibition by the allosteric effector UTP, but is no longer activated by the allosteric effector phosphoribosyl diphosphate. The linker appears to serve as a spacer that allows the complex to cycle between two conformations, an open low activity form in which the NH4+ site on the synthetase domain is accessible and an activated conformation in which the NH4+ generated in situ from Gln is directly channeled to the synthetase domain active site and access to exogenous NH4+ is blocked
Y1112L
P07259, -
aspartate transcarbamylase activity of the multifunctional mutant protein carbamylphosphate synthetase/aspartate transcarbamylase is no longer inhibited by UTP, carbamylphosphate synthetase activity retains fully sensitive to this effector
additional information
B2G3Q3
construction by gene replacement and phenotype of a carbamoylphosphate synthetase-negative mutant A17, i.e. DELTAcarB, overview. CO2 depletion or carB gene inactivation determines the auxotrophy of Streptococcus thermophilus for L-arginine and uracil. The parent strain grows faster than the mutant, even when milk is supplemented with uracil or arginine
C345A
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site-directed mutagenesis of an essential catalytic triad residue of the GATase domain, the mutation completely abolishes complementation activity and GATase activity
additional information
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disruption of Toxoplasma gondii CPSII induces a severe uracil auxotrophy with no detectable parasite replication in vitro and complete attenuation of virulence in mice. A CPSII cDNA minigene efficiently complements the uracil auxotrophy of CPSII-deficient mutants, restoring parasite growth and virulence, engineered mutations within, or proximal to, but the catalytic triad of the N-terminal glutamine amidotransferase domain inactivates the complementation activity of CPSII and demonstrates a critical dependence on the apicomplexan CPSII GATase domain in vivo
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
drug development
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CPSII is a potential parasite-selective target for drug development