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MetaCyc Enzyme: anthranilate synthase

Species: Escherichia coli K-12 substr. MG1655

Subunit composition of anthranilate synthase = [TrpE]2[TrpD]2
         anthranilate synthase component I = TrpE
         anthranilate synthase component II = TrpD (summary available)

Summary:
Anthranilate synthase (TrpDE) catalyzes the first step in the pathway of tryptophan biosynthesis, and is subject to feedback regulation by the end product of the pathway, L-tryptophan [Pabst73]. One of its component monomers also catalyzes the second step in the same pathway.

TrpDE catalyzes the glutamine amidotransferase reaction that adds an amine group from glutamine to chorismate to yield anthranilate and glutamate [Baker66, Ito69]. TrpE on its own can carry out an alternate version of this reaction, using ammonium sulfate rather than glutamine as an amino donor [Ito69]. TrpD dramatically increases the affinity of TrpE for glutamine over TrpE alone [Ito69a].

TrpDE functions as a as complex comprising two TrpD and two TrpE monomers [Li74]. In line with their role in synthesizing tryptophan, the components of this complex contain almost no tryptophan, with one residue in TrpD and none in TrpE [Nichols81].

Translation of TrpE and TrpD is coordinated via a specialized intercistronic sequence between trpE and trpD. If the latter portion of the trpE mRNA is not translated, trpD mRNA translation is markedly reduced [Nichols81].

The complex from Salmonella enterica subsp. enterica serovar Typhimurium (Salmonella typhimurium) has also been extensively studied. More recent reports have included its crystal structure 1.9 Å resolution [Morollo01], the thermodynamics of complex-catalyzed reactions [Byrnes00], intersubunit communication mechanisms [Caligiuri91], and aminodeoxyisochorismate as an enzyme-bound reaction intermediate [Morollo93].

Gene-Reaction Schematic: ?

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International


Enzymatic reaction of: anthranilate synthase

Synonyms: ASase, anthranilate synthetase

EC Number: 4.1.3.27

chorismate + L-glutamine <=> anthranilate + L-glutamate + pyruvate + H+

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

This reaction is reversible.

Alternative Substrates for L-glutamine: ammonia [Ito69 ]

In Pathways: superpathway of chorismate metabolism , superpathway of phenylalanine, tyrosine, and tryptophan biosynthesis , superpathway of tryptophan biosynthesis , tryptophan biosynthesis

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International

Summary:
Both tryptophan and 7-methyltryptophan are competitive inhibitors with respect to chorismate [Baker66, Held70].

Cofactors or Prosthetic Groups: Mg2+ [Ito69a]

Alternative Cofactors for Mg2+: Co2+ , Fe2+

Inhibitors (Competitive): 7-methyl-L-tryptophan [Held70] , L-tryptophan [Baker66, Comment 1]

Inhibitors (Noncompetitive): L-tryptophan [Baker66, Comment 2]

Primary Physiological Regulators of Enzyme Activity: L-tryptophan

Kinetic Parameters:

Substrate
Km (μM)
Citations
chorismate
1.2
[Baker66, BRENDA14]
chorismate
29.0
[Holden02, BRENDA14]
chorismate
5.5
[Ito69a]


Subunit of anthranilate synthase: anthranilate synthase component I

Synonyms: TryD, TrpE, α subunit

Gene: trpE Accession Numbers: EG11028 (MetaCyc), b1264, ECK1258

Locations: cytosol

Sequence Length: 520 AAs

Molecular Weight: 57.495 kD (from nucleotide sequence)

Molecular Weight: 60.0 kD (experimental) [Ito69]

pI: 5.57

GO Terms:

Biological Process: GO:0000162 - tryptophan biosynthetic process Inferred from experiment Inferred by computational analysis [UniProtGOA12, UniProtGOA11, Ito66, Ito69]
GO:0008152 - metabolic process Inferred by computational analysis [UniProtGOA11]
GO:0008652 - cellular amino acid biosynthetic process Inferred by computational analysis [UniProtGOA11]
GO:0009058 - biosynthetic process Inferred by computational analysis [GOA01]
GO:0009073 - aromatic amino acid family biosynthetic process Inferred by computational analysis [UniProtGOA11]
Molecular Function: GO:0004049 - anthranilate synthase activity Inferred from experiment Inferred by computational analysis [GOA01a, GOA01, Ito69]
GO:0003824 - catalytic activity Inferred by computational analysis [UniProtGOA11]
GO:0016829 - lyase activity Inferred by computational analysis [UniProtGOA11]
GO:0016833 - oxo-acid-lyase activity Inferred by computational analysis [GOA01]
GO:0046872 - metal ion binding Inferred by computational analysis [UniProtGOA11]
Cellular Component: GO:0005829 - cytosol Inferred from experiment Inferred by computational analysis [DiazMejia09, Zhang07]

MultiFun Terms: metabolism biosynthesis of building blocks amino acids tryptophan

Unification Links: EcoliWiki:b1264 , ModBase:P00895 , PR:PRO_000024121 , Pride:P00895 , Protein Model Portal:P00895 , RefSeq:NP_415780 , SMR:P00895 , String:511145.b1264 , Swiss-Model:P00895 , UniProt:P00895

Relationship Links: InterPro:IN-FAMILY:IPR005257 , InterPro:IN-FAMILY:IPR005801 , InterPro:IN-FAMILY:IPR006805 , InterPro:IN-FAMILY:IPR015890 , InterPro:IN-FAMILY:IPR019999 , Pfam:IN-FAMILY:PF00425 , Pfam:IN-FAMILY:PF04715 , Prints:IN-FAMILY:PR00095


Component enzyme of anthranilate synthase : anthranilate synthase component II

Synonyms: TrpD, TrpGD

Gene: trpD Accession Numbers: EG11027 (MetaCyc), b1263, ECK1257

Locations: cytosol

Sequence Length: 531 AAs

Molecular Weight: 56.87 kD (from nucleotide sequence)

pI: 6.47

GO Terms:

Biological Process: GO:0000162 - tryptophan biosynthetic process Inferred from experiment Inferred by computational analysis [UniProtGOA12, UniProtGOA11, GOA06, GOA01, Ito66, Gonzalez86, Ito69]
GO:0006541 - glutamine metabolic process Inferred by computational analysis [UniProtGOA11]
GO:0008152 - metabolic process Inferred by computational analysis [UniProtGOA11, GOA01]
GO:0008652 - cellular amino acid biosynthetic process Inferred by computational analysis [UniProtGOA11]
GO:0009073 - aromatic amino acid family biosynthetic process Inferred by computational analysis [UniProtGOA11]
Molecular Function: GO:0004048 - anthranilate phosphoribosyltransferase activity Inferred from experiment Inferred by computational analysis [GOA06, GOA01a, GOA01, Gonzalez86]
GO:0004049 - anthranilate synthase activity Inferred from experiment Inferred by computational analysis [GOA01a, Ito69]
GO:0000287 - magnesium ion binding Inferred by computational analysis [GOA06]
GO:0003824 - catalytic activity Inferred by computational analysis [UniProtGOA11]
GO:0016740 - transferase activity Inferred by computational analysis [UniProtGOA11]
GO:0016757 - transferase activity, transferring glycosyl groups Inferred by computational analysis [UniProtGOA11, GOA01]
GO:0016829 - lyase activity Inferred by computational analysis [UniProtGOA11]
Cellular Component: GO:0005829 - cytosol

MultiFun Terms: metabolism biosynthesis of building blocks amino acids tryptophan

Unification Links: EcoliWiki:b1263 , ModBase:P00904 , PR:PRO_000024120 , Pride:P00904 , Protein Model Portal:P00904 , RefSeq:NP_415779 , SMR:P00904 , String:511145.b1263 , Swiss-Model:P00904 , UniProt:P00904

Relationship Links: InterPro:IN-FAMILY:IPR000312 , InterPro:IN-FAMILY:IPR005940 , InterPro:IN-FAMILY:IPR006221 , InterPro:IN-FAMILY:IPR017459 , InterPro:IN-FAMILY:IPR017926 , Pfam:IN-FAMILY:PF00117 , Pfam:IN-FAMILY:PF00591 , Pfam:IN-FAMILY:PF02885 , Prosite:IN-FAMILY:PS51273

Catalyzes:
N-(5-phosphoribosyl)-anthranilate + diphosphate ↔ anthranilate + 5-phospho-α-D-ribose 1-diphosphate

Summary:
Anthranilate phosphoribosyl transferase (TrpD) catalyzes the second step in the pathway of tryptophan biosynthesis.

TrpD catalyzes a phosphoribosyltransferase reaction that generates N-(5'-phosphoribosyl)-anthranilate [Gonzalez86].

The phosphoribosyl transferase and anthranilate synthase contributing portions of TrpD are present in different portions of the protein. The anthranilate synthase reaction requires the amino-terminal portion of the protein, whereas the phosphoribosyltransferase reaction requires the carboxy-terminal region [Jackson74].


References

Baker66: Baker TI, Crawford IP (1966). "Anthranilate synthetase. Partial purification and some kinetic studies on the enzyme from Escherichia coli." J Biol Chem 241(23);5577-84. PMID: 5333199

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

Byrnes00: Byrnes WM, Goldberg RN, Holden MJ, Mayhew MP, Tewari YB (2000). "Thermodynamics of reactions catalyzed by anthranilate synthase." Biophys Chem 84(1);45-64. PMID: 10723544

Caligiuri91: Caligiuri MG, Bauerle R (1991). "Subunit communication in the anthranilate synthase complex from Salmonella typhimurium." Science 252(5014);1845-8. PMID: 2063197

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

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."

Gonzalez86: Gonzalez JE, Somerville RL (1986). "The anthranilate aggregate of Escherichia coli: kinetics of inhibition by tryptophan of phosphoribosyltransferase." Biochem Cell Biol 64(7);681-91. PMID: 2428387

Held70: Held WA, Smith OH (1970). "Mechanism of 3-methylanthranilic acid derepression of the tryptophan operon in Escherichia coli." J Bacteriol 101(1);209-17. PMID: 4904235

Holden02: Holden MJ, Mayhew MP, Gallagher DT, Vilker VL (2002). "Chorismate lyase: kinetics and engineering for stability." Biochim Biophys Acta 1594(1);160-7. PMID: 11825618

Ito66: Ito J, Yanofsky C (1966). "The nature of the anthranilic acid synthetase complex of Escherichia coli." J Biol Chem 241(17);4112-4. PMID: 5331787

Ito69: Ito J, Cox EC, Yanofsky C (1969). "Anthranilate synthetase, an enzyme specified by the tryptophan operon of Escherichia coli: purification and characterization of component I." J Bacteriol 97(2);725-33. PMID: 4886289

Ito69a: Ito J, Yanofsky C (1969). "Anthranilate synthetase, an enzyme specified by the tryptophan operon of Escherichia coli: Comparative studies on the complex and the subunits." J Bacteriol 1969;97(2);734-42. PMID: 4886290

Jackson74: Jackson EN, Yanofsky C (1974). "Localization of two functions of the phosphoribosyl anthranilate transferase of Escherichia coli to distinct regions of the polypeptide chain." J Bacteriol 117(2);502-8. PMID: 4590474

Li74: Li SL, Hanlon J, Yanofsky C (1974). "Separation of anthranilate synthetase components I and II of Escherichia coli, Salmonella typhimurium, and Serratia marcescens and determination of their amino-terminal sequences by automatic Edman degradation." Biochemistry 1974;13(8);1736-44. PMID: 4598537

Morollo01: Morollo AA, Eck MJ (2001). "Structure of the cooperative allosteric anthranilate synthase from Salmonella typhimurium." Nat Struct Biol 8(3);243-7. PMID: 11224570

Morollo93: Morollo AA, Bauerle R (1993). "Characterization of composite aminodeoxyisochorismate synthase and aminodeoxyisochorismate lyase activities of anthranilate synthase." Proc Natl Acad Sci U S A 90(21);9983-7. PMID: 8234345

Nichols81: Nichols BP, van Cleemput M, Yanofsky C (1981). "Nucleotide sequence of Escherichia coli trpE. Anthranilate synthetase component I contains no tryptophan residues." J Mol Biol 1981;146(1);45-54. PMID: 7021857

Pabst73: Pabst MJ, Kuhn JC, Somerville RL (1973). "Feedback regulation in the anthranilate aggregate from wild type and mutant strains of Escherichia coli." J Biol Chem 248(3);901-14. PMID: 4567790

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."

Zhang07: Zhang N, Chen R, Young N, Wishart D, Winter P, Weiner JH, Li L (2007). "Comparison of SDS- and methanol-assisted protein solubilization and digestion methods for Escherichia coli membrane proteome analysis by 2-D LC-MS/MS." Proteomics 7(4);484-93. PMID: 17309111


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Thu Dec 18, 2014, BIOCYC14B.