Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
twitter

Escherichia coli K-12 substr. MG1655 Enzyme: carbamoyl phosphate synthetase

Subunit composition of carbamoyl phosphate synthetase = [CarB]2[CarA]2
         carbamoyl phosphate synthetase, β chain = CarB (summary available)
         carbamoyl phosphate synthetase, α chain = CarA (summary available)

Summary:
Carbamoyl phosphate synthetase from E. coli catalyzes the first committed step in the separate biosynthetic pathways for the production of arginine, and pyrimidine nucleotides. The enzyme is an α,β-heterodimer consisting of a small amidotransferase subunit complexed to a larger synthetase subunit. The small subunit, encoded by carA gene hydrolyzes glutamine to glutamate and ammonia. The large subunit, encoded by carB gene binds the two required molecules of MgATP and catalyzes the two required phosphorylation events. The small subunit contains a catalytic triad (Cys269, His353 and Glu355) situated between the two structural domains. The large subunit consists of four structural units: the carboxyphosphate synthetic component, the oligomerization domain, the carbamoyl phosphate synthetic component and the allosteric domain [Thoden99].

The enzyme contains a total of three separate active sites that are connected by an intramolecular tunnel. The small subunit harbors one of these active sites. Two molecular tunnels connect the three active sites contained within the small and large subunits. The ammonia tunnel extends from the active site of the small subunit to the active site of the carboxy phosphate domain of the large subunit. The carbamate tunnel connects the two active sites within the large subunit [Thoden04].

The active sites of the enzyme are very resistant toward changes in nucleotide specificity, most likely owing to the presence of the K+-binding loop that prevents binding of GTP. Mutations at positions 144 and 690 interfere with access of substrate to the active sites [Kothe04].

Site directed mutagenesis showed that either a C269G or C269S mutation results in loss of all of the glutamine-dependent synthesis of carbamoylphosphate though the enzyme still retains the ability to use ammonia as the nitrogen source [Rubino87]. Mutagenesis of residues Glu783, Glu892 and Thr1042 that had been shown by crystallography to interact with bound ornithine demonstrated their importance for ornithine binding and provided insight into the mechanism of allosteric control of enzyme activity [Rochera02]. Site-directed mutagenesis studies also suggested that Cys269 and His353 of the conserved catalytic triad in the glutamine aminotransferase site may function as a catalytic dyad [Hart08]. The transfer of ammonia through the ammonia tunnel in this enzyme was investigated using a combination of molecular dynamics simulations and experimental characterization of mutations [Fan09]. This approach was also used to characterize the transport of carbamate through the large subunit of this enzyme [Lund10]. In another mutagenesis study, substiturion of six intrinsic tryptophan residues in the enzyme with tyrosine created a tryptophan-free variant. Subsequent substitutions of individual tryptophan residues at each site allowed their use as fluoresence probes to study conformational changes [Johnson07].

The large subunit contains the sites for the allosteric activators (NH4+, IMP, ornithine) and the inhibitor UMP [Trotta74]. Two residues, serine 948 and threonine 1042, appear crucial for allosteric regulation of the enzyme [Delannay99].

Gene-Reaction Schematic: ?

Credits:
Last-Curated ? 30-Mar-2011 by Fulcher C , SRI International


Enzymatic reaction of: carbamoyl phosphate synthetase

Synonyms: carbamoyl-phosphate synthetase (glutamine-hydrolysing), glutamine-dependent carbamoyl-phosphate synthase, GD-CPSase, carbon-dioxide:L-glutamine amido-ligase (ADP-forming,carbamate-phosphorylating)

EC Number: 6.3.5.5

2 ATP + L-glutamine + hydrogen carbonate + H2O <=> carbamoyl-phosphate + L-glutamate + 2 ADP + phosphate + 2 H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is physiologically favored in the direction shown.

In Pathways: glutamine degradation I , superpathway of arginine and polyamine biosynthesis , superpathway of histidine, purine, and pyrimidine biosynthesis , superpathway of pyrimidine deoxyribonucleotides de novo biosynthesis , superpathway of pyrimidine ribonucleotides de novo biosynthesis , arginine biosynthesis I (via L-ornithine) , UMP biosynthesis

Summary:
The enzyme catalyzes the assembly of carbamoyl phosphate via a mechanism that requires at least four separate chemical reactions: phosphorylation of bicarbonate to carboxyphosphate; hydrolysis of glutamine to glutamate and ammonia; a nucleophilic attack of ammonia on carboxyphosphate yielding carbamate; and finally the phosphorylation of carbamate forming carbamoyl phosphate [Thoden99].

In addition to the Mg+2 needed to complex with the nucleotide substrate, free Mg+2 is an absolute requirement for activity. Other ions also bind at the divalent cation site and the nucleotide site [Raushel79].

In vitro the enzyme also catalyzed ATP synthesis from carbamoyl-phosphate and ADP in the reverse direction [Guillou92].

Cofactors or Prosthetic Groups: Mg2+ [Comment 1, Raushel79]

Alternative Cofactors for Mg2+: Mn2+ , Co2+ , Cd2+ , Zn2+

Activators (Allosteric): ammonium [Anderson77, Trotta74] , IMP [Anderson77, Trotta74] , L-ornithine [Anderson77, Trotta74]

Activators (Unknown Mechanism): K+ [Thoden99]

Inhibitors (Allosteric): UMP [Trotta74]

Inhibitors (Competitive): cyanate [Helmward89, Comment 2]

Inhibitors (Unknown Mechanism): acivicin [Helmward89] , 6-diazo-5-oxo-norvaline [Helmward89] , 6-diazo-5-oxonorleucine [Helmward89, Khedouri66] , L-azaserine [Helmward89, Khedouri66] , L-2-amino-4-oxo-5-chloropentanoate [Helmward89, Khedouri66]

Primary Physiological Regulators of Enzyme Activity: IMP , L-ornithine , UMP

Kinetic Parameters:

Substrate
Km (μM)
kcat (sec-1)
kcat/Km (sec-1 μM-1)
Citations
ADP
0.13
[Lund10, BRENDA14]
L-glutamine
120.0
[Kim04a, BRENDA14]
L-glutamine
150.0
[Rishavy00, BRENDA14]
L-glutamine
361.0, 890.0, 910.0, 1075.0, 1490.0, 1860.0
[Eroglu02, BRENDA14]
L-glutamine
130.0
2.13
[Hart08, BRENDA14]
L-glutamine
170.0
9.4
[SaeedKothe03, BRENDA14]
ATP
220.0, 320.0
[Yefimenko05, BRENDA14]
ATP
440.0
[Johnson07, BRENDA14]
ATP
10.0
[Guillou92]
ATP
51.0, 240.0
3.6
[Lund10, BRENDA14]
ATP
5.0, 29.0
4.04
[Kothe04, BRENDA14]
ATP
44.0
4.79
[Hart08, BRENDA14]
ATP
50.0, 60.0
2.2, 6.8
[SaeedKothe03, BRENDA14]
ATP
430.0, 460.0
3.35, 8.0
[Sahay98, BRENDA14]
hydrogen carbonate
1330.0, 1900.0
[Yefimenko05, BRENDA14]
hydrogen carbonate
640.0
[Guillou92]

pH(opt): 4.2 [BRENDA14, Rishavy00], 7.8 [BRENDA14, Meister89], 9.3 [BRENDA14, Rishavy00], 9.5 [BRENDA14, Meister89]


Subunit of carbamoyl phosphate synthetase: carbamoyl phosphate synthetase, β chain

Synonyms: CarB, Cap, PyrA, β chain, large chain

Gene: carB Accession Numbers: EG10135 (EcoCyc), b0033, ECK0034

Locations: cytosol

Sequence Length: 1073 AAs

Molecular Weight: 117.84 kD (from nucleotide sequence)

pI: 5.43

GO Terms:

Biological Process: GO:0008652 - cellular amino acid biosynthetic process Inferred from experiment Inferred by computational analysis [UniProtGOA11, Guillou92]
GO:0019856 - pyrimidine nucleobase biosynthetic process Inferred from experiment [Guillou92]
GO:0042710 - biofilm formation Inferred from experiment [Garavaglia12]
GO:0006221 - pyrimidine nucleotide biosynthetic process Inferred by computational analysis [UniProtGOA11]
GO:0006526 - arginine biosynthetic process Inferred by computational analysis [UniProtGOA12, UniProtGOA11]
GO:0006807 - nitrogen compound metabolic process Inferred by computational analysis [GOA01]
GO:0008152 - metabolic process Inferred by computational analysis [GOA01]
GO:0044205 - 'de novo' UMP biosynthetic process Inferred by computational analysis [UniProtGOA12]
Molecular Function: GO:0000166 - nucleotide binding Inferred from experiment Inferred by computational analysis [UniProtGOA11, Mareya95, Fresquet00]
GO:0004087 - carbamoyl-phosphate synthase (ammonia) activity Inferred from experiment [Rubino87]
GO:0005515 - protein binding Inferred from experiment [Rajagopala14, Marsh13, Thoden98, Thoden99a, Thoden99b, Thoden02, Butland05]
GO:0005524 - ATP binding Inferred from experiment Inferred by computational analysis [UniProtGOA11, GOA01, Guillou92, Kothe04]
GO:0016597 - amino acid binding Inferred from experiment [Mareya95]
GO:0046872 - metal ion binding Inferred from experiment Inferred by computational analysis [UniProtGOA11, GOA01, Raushel79]
GO:0003824 - catalytic activity Inferred by computational analysis [GOA01]
GO:0004088 - carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity Inferred by computational analysis [GOA01a]
GO:0016874 - ligase activity Inferred by computational analysis [UniProtGOA11]
Cellular Component: GO:0005829 - cytosol Inferred from experiment Inferred by computational analysis [DiazMejia09, Ishihama08, LopezCampistrou05]
GO:0005951 - carbamoyl-phosphate synthase complex Inferred from experiment [Trotta74]

MultiFun Terms: metabolism biosynthesis of building blocks amino acids arginine
metabolism biosynthesis of building blocks nucleotides pyrimidine biosynthesis

Isozyme Sequence Similarity [Comment 3]:

Unification Links: DIP:DIP-1025N , EcoliWiki:b0033 , Mint:MINT-1255866 , ModBase:P00968 , PR:PRO_000022248 , Pride:P00968 , Protein Model Portal:P00968 , RefSeq:NP_414574 , SMR:P00968 , String:511145.b0033 , UniProt:P00968

Relationship Links: InterPro:IN-FAMILY:IPR005479 , InterPro:IN-FAMILY:IPR005480 , InterPro:IN-FAMILY:IPR005481 , InterPro:IN-FAMILY:IPR005483 , InterPro:IN-FAMILY:IPR006275 , InterPro:IN-FAMILY:IPR011607 , InterPro:IN-FAMILY:IPR011761 , InterPro:IN-FAMILY:IPR013815 , InterPro:IN-FAMILY:IPR013816 , InterPro:IN-FAMILY:IPR016185 , PDB:Structure:1A9X , PDB:Structure:1BXR , PDB:Structure:1C30 , PDB:Structure:1C3O , PDB:Structure:1CE8 , PDB:Structure:1CS0 , PDB:Structure:1JDB , PDB:Structure:1KEE , PDB:Structure:1M6V , PDB:Structure:1T36 , Pfam:IN-FAMILY:PF00289 , Pfam:IN-FAMILY:PF02142 , Pfam:IN-FAMILY:PF02786 , Pfam:IN-FAMILY:PF02787 , Prints:IN-FAMILY:PR00098 , Prosite:IN-FAMILY:PS00866 , Prosite:IN-FAMILY:PS00867 , Prosite:IN-FAMILY:PS50975 , Smart:IN-FAMILY:SM00851 , Smart:IN-FAMILY:SM01096

Summary:
In E. coli, the large subunit encoded by carB gene is the synthetase component of the enzyme. It binds the two required molecules of MgATP and catalyzes the two required phosphorylation events. The large subunit consists of four structural units: the carboxyphosphate synthetic component, the oligomerization domain, the carbamoyl phosphate synthetic component and the allosteric domain [Thoden99]. The large subunit alone can catalyze carbamyl phosphate synthesis from ammonia, but not from glutamine [Rubino87]. It uses NH3 and HCO3- in an ATP-dependent reaction to form carbamoyl phosphate [Guillou89]. This subunit has two catalytic nucleotide-binding domains, one involved in the activation of HCO3- and the second in phosphorylation of carbamate. Glu841 is an essential residue for the phosphorylation of carbamate in the terminal step of the catalytic mechanism [Guillou92].

Essentiality data for carB knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB enriched Yes 37 Aerobic 6.95   Yes [Gerdes03, Comment 4]
LB Lennox Yes 37 Aerobic 7   Yes [Baba06, Comment 5]
M9 medium with 0.4% glucose No 37 Aerobic 7.2 0.27 No [Patrick07, Comment 6]
M9 medium with 1% glycerol No 37 Aerobic 7.2 0.35 No [Joyce06]
MOPS medium with 0.4% glucose No 37 Aerobic 7.2 0.22 No [Baba06, Comment 5]
No [Feist07, Comment 7]

Subunit of carbamoyl phosphate synthetase: carbamoyl phosphate synthetase, α chain

Synonyms: CarA, Arg, Cap, PyrA, α chain, small chain

Gene: carA Accession Numbers: EG10134 (EcoCyc), b0032, ECK0033

Locations: cytosol

Sequence Length: 382 AAs

Molecular Weight: 41.431 kD (from nucleotide sequence)

pI: 6.3

GO Terms:

Biological Process: GO:0006207 - 'de novo' pyrimidine nucleobase biosynthetic process Inferred from experiment [Pierard64]
GO:0006526 - arginine biosynthetic process Inferred from experiment Inferred by computational analysis [UniProtGOA12, UniProtGOA11, GOA06, Pierard64]
GO:0006541 - glutamine metabolic process Inferred from experiment Inferred by computational analysis [UniProtGOA11, GOA06, Mullins91]
GO:0006221 - pyrimidine nucleotide biosynthetic process Inferred by computational analysis [UniProtGOA11, GOA06]
GO:0006543 - glutamine catabolic process Inferred by computational analysis [GOA01]
GO:0008652 - cellular amino acid biosynthetic process Inferred by computational analysis [UniProtGOA11]
GO:0044205 - 'de novo' UMP biosynthetic process Inferred by computational analysis [UniProtGOA12]
GO:0070409 - carbamoyl phosphate biosynthetic process Inferred by computational analysis [GOA01]
Molecular Function: GO:0005515 - protein binding Inferred from experiment [Rajagopala14, Marsh13, Thoden98, Thoden99a, Thoden99b, Thoden02, Butland05]
GO:0000166 - nucleotide binding Inferred by computational analysis [UniProtGOA11]
GO:0004088 - carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity Inferred by computational analysis [GOA06, GOA01a]
GO:0005524 - ATP binding Inferred by computational analysis [UniProtGOA11, GOA06]
GO:0016874 - ligase activity Inferred by computational analysis [UniProtGOA11]
Cellular Component: GO:0005737 - cytoplasm Inferred from experiment [Guillou89]
GO:0005829 - cytosol Inferred from experiment Inferred by computational analysis [DiazMejia09, Ishihama08, LopezCampistrou05, Lasserre06]
GO:0005951 - carbamoyl-phosphate synthase complex Inferred from experiment [Trotta74]

MultiFun Terms: metabolism biosynthesis of building blocks amino acids arginine
metabolism biosynthesis of building blocks nucleotides pyrimidine biosynthesis

Unification Links: DIP:DIP-35412N , EcoliWiki:b0032 , ModBase:P0A6F1 , PR:PRO_000022247 , Pride:P0A6F1 , Protein Model Portal:P0A6F1 , RefSeq:NP_414573 , SMR:P0A6F1 , String:511145.b0032 , UniProt:P0A6F1

Relationship Links: InterPro:IN-FAMILY:IPR002474 , InterPro:IN-FAMILY:IPR006274 , InterPro:IN-FAMILY:IPR017926 , PDB:Structure:1A9X , PDB:Structure:1BXR , PDB:Structure:1C30 , PDB:Structure:1C3O , PDB:Structure:1CE8 , PDB:Structure:1CS0 , PDB:Structure:1JDB , PDB:Structure:1KEE , PDB:Structure:1M6V , PDB:Structure:1T36 , Pfam:IN-FAMILY:PF00117 , Pfam:IN-FAMILY:PF00988 , Prosite:IN-FAMILY:PS51273 , Smart:IN-FAMILY:SM01097

Summary:
In E. coli, the small subunit encoded by carA gene is the amidotransferase component of the enzyme. It hydrolyzes glutamine to glutamate and ammonia. The small subunit contains a catalytic triad (Cys269, His353 and Glu355) situated between the two structural domains [Thoden99]. The small subunit is protected from proteolysis by the large subunit [Mareya95]. The mechanism for glutamine hydrolysis on the small subunit requires the participation of an essential sulfhydryl group for the formation of a thioester intermediate [Rubino87].

Essentiality data for carA knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB enriched Yes 37 Aerobic 6.95   Yes [Gerdes03, Comment 4]
LB Lennox Yes 37 Aerobic 7   Yes [Baba06, Comment 5]
M9 medium with 0.4% glucose No 37 Aerobic 7.2 0.27 No [Patrick07, Comment 6]
M9 medium with 1% glycerol No 37 Aerobic 7.2 0.35 No [Joyce06]
MOPS medium with 0.4% glucose No 37 Aerobic 7.2 0.22 No [Baba06, Comment 5]
No [Feist07, Comment 7]

References

Anderson75: Anderson PM, Carlson JD (1975). "Reversible reaction of cyanate with a reactive sulfhydryl group at the glutamine binding site of carbamyl phosphate synthetase." Biochemistry 1975;14(16);3688-94. PMID: 240389

Anderson77: Anderson PM (1977). "Binding of allosteric effectors to carbamyl-phosphate synthetase from Escherichia coli." Biochemistry 1977;16(4);587-93. PMID: 189806

Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554

BRENDA14: BRENDA team (2014). "Imported from BRENDA version existing on Aug 2014." http://www.brenda-enzymes.org.

Butland05: Butland G, Peregrin-Alvarez JM, Li J, Yang W, Yang X, Canadien V, Starostine A, Richards D, Beattie B, Krogan N, Davey M, Parkinson J, Greenblatt J, Emili A (2005). "Interaction network containing conserved and essential protein complexes in Escherichia coli." Nature 433(7025);531-7. PMID: 15690043

Delannay99: Delannay S, Charlier D, Tricot C, Villeret V, Pierard A, Stalon V (1999). "Serine 948 and threonine 1042 are crucial residues for allosteric regulation of Escherichia coli carbamoylphosphate synthetase and illustrate coupling effects of activation and inhibition pathways." J Mol Biol 286(4);1217-28. PMID: 10047492

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Eroglu02: Eroglu B, Powers-Lee SG (2002). "Unmasking a functional allosteric domain in an allosterically nonresponsive carbamoyl-phosphate synthetase." J Biol Chem 277(47);45466-72. PMID: 12244118

Fan09: Fan Y, Lund L, Shao Q, Gao YQ, Raushel FM (2009). "A combined theoretical and experimental study of the ammonia tunnel in carbamoyl phosphate synthetase." J Am Chem Soc 131(29);10211-9. PMID: 19569682

Feist07: Feist AM, Henry CS, Reed JL, Krummenacker M, Joyce AR, Karp PD, Broadbelt LJ, Hatzimanikatis V, Palsson BO (2007). "A genome-scale metabolic reconstruction for Escherichia coli K-12 MG1655 that accounts for 1260 ORFs and thermodynamic information." Mol Syst Biol 3;121. PMID: 17593909

Fresquet00: Fresquet V, Mora P, Rochera L, Ramon-Maiques S, Rubio V, Cervera J (2000). "Site-directed mutagenesis of the regulatory domain of Escherichia coli carbamoyl phosphate synthetase identifies crucial residues for allosteric regulation and for transduction of the regulatory signals." J Mol Biol 299(4);979-91. PMID: 10843852

Garavaglia12: Garavaglia M, Rossi E, Landini P (2012). "The pyrimidine nucleotide biosynthetic pathway modulates production of biofilm determinants in Escherichia coli." PLoS One 7(2);e31252. PMID: 22359582

Gerdes03: Gerdes SY, Scholle MD, Campbell JW, Balazsi G, Ravasz E, Daugherty MD, Somera AL, Kyrpides NC, Anderson I, Gelfand MS, Bhattacharya A, Kapatral V, D'Souza M, Baev MV, Grechkin Y, Mseeh F, Fonstein MY, Overbeek R, Barabasi AL, Oltvai ZN, Osterman AL (2003). "Experimental determination and system level analysis of essential genes in Escherichia coli MG1655." J Bacteriol 185(19);5673-84. PMID: 13129938

GOA01: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA01a: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA06: GOA, SIB (2006). "Electronic Gene Ontology annotations created by transferring manual GO annotations between orthologous microbial proteins."

Guillou89: Guillou F, Rubino SD, Markovitz RS, Kinney DM, Lusty CJ (1989). "Escherichia coli carbamoyl-phosphate synthetase: domains of glutaminase and synthetase subunit interaction." Proc Natl Acad Sci U S A 86(21);8304-8. PMID: 2682645

Guillou92: Guillou F, Liao M, Garcia-Espana A, Lusty CJ (1992). "Mutational analysis of carbamyl phosphate synthetase. Substitution of Glu841 leads to loss of functional coupling between the two catalytic domains of the synthetase subunit." Biochemistry 1992;31(6);1656-64. PMID: 1737023

Hart08: Hart EJ, Powers-Lee SG (2008). "Mutation analysis of carbamoyl phosphate synthetase: does the structurally conserved glutamine amidotransferase triad act as a functional dyad?." Protein Sci 17(7);1120-8. PMID: 18458150

Helmward89: Helmward Z "Handbook of Enzyme Inhibitors. 2nd, revised and enlarged edition." Weinheim, Federal Republic of Germany ; New York, NY, USA , 1989.

Ishihama08: Ishihama Y, Schmidt T, Rappsilber J, Mann M, Hartl FU, Kerner MJ, Frishman D (2008). "Protein abundance profiling of the Escherichia coli cytosol." BMC Genomics 9;102. PMID: 18304323

Johnson07: Johnson JL, West JK, Nelson AD, Reinhart GD (2007). "Resolving the fluorescence response of Escherichia coli carbamoyl phosphate synthetase: mapping intra- and intersubunit conformational changes." Biochemistry 46(2);387-97. PMID: 17209549

Joyce06: Joyce AR, Reed JL, White A, Edwards R, Osterman A, Baba T, Mori H, Lesely SA, Palsson BO, Agarwalla S (2006). "Experimental and computational assessment of conditionally essential genes in Escherichia coli." J Bacteriol 188(23);8259-71. PMID: 17012394

Khedouri66: Khedouri E, Anderson PM, Meister A (1966). "Selective inactivation of the glutamine binding site of Escherichia coli carbamyl phosphate synthetase by 2-amino-4-oxo-5-chloropentanoic acid." Biochemistry 1966;5(11);3552-7. PMID: 5339592

Kim04a: Kim J, Raushel FM (2004). "Access to the carbamate tunnel of carbamoyl phosphate synthetase." Arch Biochem Biophys 425(1);33-41. PMID: 15081891

Kothe04: Kothe M, Powers-Lee SG (2004). "Nucleotide recognition in the ATP-grasp protein carbamoyl phosphate synthetase." Protein Sci 13(2);466-75. PMID: 14718657

Lasserre06: Lasserre JP, Beyne E, Pyndiah S, Lapaillerie D, Claverol S, Bonneu M (2006). "A complexomic study of Escherichia coli using two-dimensional blue native/SDS polyacrylamide gel electrophoresis." Electrophoresis 27(16);3306-21. PMID: 16858726

LopezCampistrou05: Lopez-Campistrous A, Semchuk P, Burke L, Palmer-Stone T, Brokx SJ, Broderick G, Bottorff D, Bolch S, Weiner JH, Ellison MJ (2005). "Localization, annotation, and comparison of the Escherichia coli K-12 proteome under two states of growth." Mol Cell Proteomics 4(8);1205-9. PMID: 15911532

Lund10: Lund L, Fan Y, Shao Q, Gao YQ, Raushel FM (2010). "Carbamate transport in carbamoyl phosphate synthetase: a theoretical and experimental investigation." J Am Chem Soc 132(11);3870-8. PMID: 20187643

Mareya95: Mareya SM, Raushel FM (1995). "Mapping the structural domains of E. coli carbamoyl phosphate synthetase using limited proteolysis." Bioorg Med Chem 3(5);525-32. PMID: 7648201

Marsh13: Marsh JA, Hernandez H, Hall Z, Ahnert SE, Perica T, Robinson CV, Teichmann SA (2013). "Protein complexes are under evolutionary selection to assemble via ordered pathways." Cell 153(2);461-70. PMID: 23582331

Meister89: Meister A (1989). "Mechanism and regulation of the glutamine-dependent carbamyl phosphate synthetase of Escherichia coli." Adv Enzymol Relat Areas Mol Biol 62;315-74. PMID: 2658488

Mullins91: Mullins LS, Lusty CJ, Raushel FM (1991). "Alterations in the energetics of the carbamoyl phosphate synthetase reaction by site-directed modification of the essential sulfhydryl group." J Biol Chem 266(13);8236-40. PMID: 1827118

Nyunoya83: Nyunoya H, Lusty CJ (1983). "The carB gene of Escherichia coli: a duplicated gene coding for the large subunit of carbamoyl-phosphate synthetase." Proc Natl Acad Sci U S A 1983;80(15);4629-33. PMID: 6308632

Patrick07: Patrick WM, Quandt EM, Swartzlander DB, Matsumura I (2007). "Multicopy suppression underpins metabolic evolvability." Mol Biol Evol 24(12);2716-22. PMID: 17884825

Pierard64: Pierard A, Wiame JM (1964). "Regulation and mutation affecting a glutamine dependent formation of carbamyl phosphate in Escherichia coli." Biochem Biophys Res Commun 15(1);76-81. PMID: 5319709

Rajagopala14: Rajagopala SV, Sikorski P, Kumar A, Mosca R, Vlasblom J, Arnold R, Franca-Koh J, Pakala SB, Phanse S, Ceol A, Hauser R, Siszler G, Wuchty S, Emili A, Babu M, Aloy P, Pieper R, Uetz P (2014). "The binary protein-protein interaction landscape of Escherichia coli." Nat Biotechnol 32(3);285-90. PMID: 24561554

Raushel79: Raushel FM, Rawding CJ, Anderson PM, Villafranca JJ (1979). "Paramagnetic probes for carbamoyl-phosphate synthetase: metal ion binding studies and preparation of nitroxide spin-labeled derivatives." Biochemistry 1979;18(25);5562-6. PMID: 229896

Rishavy00: Rishavy MA, Cleland WW, Lusty CJ (2000). "15N isotope effects in glutamine hydrolysis catalyzed by carbamyl phosphate synthetase: evidence for a tetrahedral intermediate in the mechanism." Biochemistry 39(24);7309-15. PMID: 10852731

Rochera02: Rochera L, Fresquet V, Rubio V, Cervera J (2002). "Mechanism of allosteric modulation of Escherichia coli carbamoyl phosphate synthetase probed by site-directed mutagenesis of ornithine site residues." FEBS Lett 514(2-3);323-8. PMID: 11943174

Rubino87: Rubino SD, Nyunoya H, Lusty CJ (1987). "In vivo synthesis of carbamyl phosphate from NH3 by the large subunit of Escherichia coli carbamyl phosphate synthetase." J Biol Chem 1987;262(9);4382-6. PMID: 3549732

SaeedKothe03: Saeed-Kothe A, Powers-Lee SG (2003). "Gain of glutaminase function in mutants of the ammonia-specific frog carbamoyl phosphate synthetase." J Biol Chem 278(29);26722-6. PMID: 12738780

Sahay98: Sahay N, Guy HI, Liu X, Evans DR (1998). "Regulation of an Escherichia coli/mammalian chimeric carbamoyl-phosphate synthetase." J Biol Chem 273(47);31195-202. PMID: 9813025

Thoden02: Thoden JB, Huang X, Raushel FM, Holden HM (2002). "Carbamoyl-phosphate synthetase. Creation of an escape route for ammonia." J Biol Chem 277(42);39722-7. PMID: 12130656

Thoden04: Thoden JB, Huang X, Kim J, Raushel FM, Holden HM (2004). "Long-range allosteric transitions in carbamoyl phosphate synthetase." Protein Sci 13(9);2398-405. PMID: 15322282

Thoden98: Thoden JB, Miran SG, Phillips JC, Howard AJ, Raushel FM, Holden HM (1998). "Carbamoyl phosphate synthetase: caught in the act of glutamine hydrolysis." Biochemistry 37(25);8825-31. PMID: 9636022

Thoden99: Thoden JB, Raushel FM, Benning MM, Rayment I, Holden HM (1999). "The structure of carbamoyl phosphate synthetase determined to 2.1 A resolution." Acta Crystallogr D Biol Crystallogr 1999;55 ( Pt 1);8-24. PMID: 10089390

Thoden99a: Thoden JB, Raushel FM, Wesenberg G, Holden HM (1999). "The binding of inosine monophosphate to Escherichia coli carbamoyl phosphate synthetase." J Biol Chem 274(32);22502-7. PMID: 10428826

Thoden99b: Thoden JB, Wesenberg G, Raushel FM, Holden HM (1999). "Carbamoyl phosphate synthetase: closure of the B-domain as a result of nucleotide binding." Biochemistry 38(8);2347-57. PMID: 10029528

Trotta74: Trotta PP, Pinkus LM, Haschemeyer RH, Meister A (1974). "Reversible dissociation of the monomer of glutamine-dependent carbamyl phosphate synthetase into catalytically active heavy and light subunits." J Biol Chem 1974;249(2);492-9. PMID: 4358555

UniProtGOA11: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

UniProtGOA12: UniProt-GOA (2012). "Gene Ontology annotation based on UniPathway vocabulary mapping."

Yefimenko05: Yefimenko I, Fresquet V, Marco-Marin C, Rubio V, Cervera J (2005). "Understanding carbamoyl phosphate synthetase deficiency: impact of clinical mutations on enzyme functionality." J Mol Biol 349(1);127-41. PMID: 15876373


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
Page generated by SRI International Pathway Tools version 18.5 on Sun Dec 21, 2014, biocyc13.