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Escherichia coli K-12 substr. MG1655 Enzyme: tyrosine aminotransferase



Gene: tyrB Accession Numbers: EG11040 (EcoCyc), b4054, ECK4046

Synonyms: tyrosine aminotransferase, tyrosine-repressible, PLP-dependent

Regulation Summary Diagram: ?

Subunit composition of tyrosine aminotransferase = [TyrB]2

Summary:
Tyrosine aminotransferase (TyrB), also known as aromatic-amino acid aminotransferase, is a broad-specificity enzyme that catalyzes the final step in tyrosine, leucine, and phenylalanine biosynthesis. TyrB catalyzes the transamination of 2-ketoisocaproate, p-hydroxyphenylpyruvate, and phenylpyruvate to yield leucine, tyrosine, and phenylalanine, respectively [Collier72, Gelfand77, Mavrides75, Powell78a].

TyrB overlaps with the catalytic activities of branched-chain amino-acid aminotransferase (IlvE), which also produces leucine, and aspartate aminotransferase, PLP-dependent (AspC), which also produces phenylalanine. In the latter case, however, TyrB is 1,000-fold more active toward aromatic substrates than AspC [Hayashi93].

TyrB is repressible by two of its products, leucine and tyrosine, and a precursor in the leucine biosynthesis pathway, keto-isovalerate [Collier72, Powell78a, Vartak91]. The last case has been shown to occur by direct inhibition of TyrB enzymatic function [Vartak91].

The mechanism of action of TyrB has been examined, especially around the PLP-binding site [Islam00, Iwasaki94]. The nature of TyrB substrate specificity has also been studied [Onuffer95, Hayashi96].

TyrB exists as a dimer [Powell78]. A crystal structure of TyrB with bound PLP has been determined to 3.5 Å resolution [Ko99].

TyrB has been shown to be useful in the preparation of enantiomerically pure β-heterocylic D-alanine derivatives by a chemo-enzymatic synthesis method. Such derivatives are of potential use in the pharmaceutical industry [Cho04].

Citations: [Gelfand77a, Kuramitsu85a, Fotheringham86]

Gene Citations: [Yang87, Fotheringham86]

Locations: cytosol

Map Position: [4,265,137 -> 4,266,330] (91.93 centisomes)
Length: 1194 bp / 397 aa

Molecular Weight of Polypeptide: 43.538 kD (from nucleotide sequence)

Molecular Weight of Multimer: 88 kD (experimental) [Mavrides75]

pI: 4.6 [Mavrides75]

Unification Links: ASAP:ABE-0013278 , CGSC:57 , EchoBASE:EB1033 , EcoGene:EG11040 , EcoliWiki:b4054 , ModBase:P04693 , OU-Microarray:b4054 , PortEco:tyrB , PR:PRO_000024151 , Pride:P04693 , Protein Model Portal:P04693 , RefSeq:NP_418478 , RegulonDB:EG11040 , SMR:P04693 , String:511145.b4054 , UniProt:P04693

Relationship Links: InterPro:IN-FAMILY:IPR000796 , InterPro:IN-FAMILY:IPR004838 , InterPro:IN-FAMILY:IPR004839 , InterPro:IN-FAMILY:IPR015421 , InterPro:IN-FAMILY:IPR015424 , Panther:IN-FAMILY:PTHR11879 , PDB:Structure:3FSL , PDB:Structure:3TAT , Pfam:IN-FAMILY:PF00155 , Prints:IN-FAMILY:PR00799 , Prosite:IN-FAMILY:PS00105

Gene-Reaction Schematic: ?

Instance reaction of [an aromatic amino acid + 2-oxoglutarate ↔ an aromatic oxo-acid + L-glutamate] (2.6.1.57):
i1: L-tyrosine + 2-oxoglutarate ↔ 4-hydroxyphenylpyruvate + L-glutamate (2.6.1.5/2.6.1.57)

Genetic Regulation Schematic: ?

GO Terms:

Biological Process: GO:0006532 - aspartate biosynthetic process Inferred from experiment [Gelfand77]
GO:0009098 - leucine biosynthetic process Inferred from experiment [Powell78a]
GO:0019292 - tyrosine biosynthetic process from chorismate via 4-hydroxyphenylpyruvate Inferred from experiment [Mavrides75]
GO:0033585 - L-phenylalanine biosynthetic process from chorismate via phenylpyruvate Inferred from experiment [Mavrides75]
GO:0006520 - cellular amino acid metabolic process Inferred by computational analysis [GOA01a]
GO:0006571 - tyrosine biosynthetic process Inferred by computational analysis [UniProtGOA12]
GO:0008652 - cellular amino acid biosynthetic process Inferred by computational analysis [UniProtGOA11a]
GO:0009058 - biosynthetic process Inferred by computational analysis [GOA01a]
GO:0009073 - aromatic amino acid family biosynthetic process Inferred by computational analysis [UniProtGOA11a]
GO:0009094 - L-phenylalanine biosynthetic process Inferred by computational analysis [UniProtGOA12]
Molecular Function: GO:0004838 - L-tyrosine:2-oxoglutarate aminotransferase activity Inferred from experiment [Mavrides75, Gelfand77]
GO:0008793 - aromatic-amino-acid:2-oxoglutarate aminotransferase activity Inferred from experiment Inferred by computational analysis [GOA01, Mavrides75]
GO:0030170 - pyridoxal phosphate binding Inferred from experiment Inferred by computational analysis [GOA01a, Powell78]
GO:0042803 - protein homodimerization activity Inferred from experiment [Powell78]
GO:0050048 - L-leucine:2-oxoglutarate aminotransferase activity Inferred from experiment [Powell78a]
GO:0003824 - catalytic activity Inferred by computational analysis [GOA01a]
GO:0004084 - branched-chain-amino-acid transaminase activity Inferred by computational analysis
GO:0008483 - transaminase activity Inferred by computational analysis [UniProtGOA11a, GOA01a]
GO:0016740 - transferase activity Inferred by computational analysis [UniProtGOA11a]
GO:0080130 - L-phenylalanine:2-oxoglutarate aminotransferase activity Inferred by computational analysis [GOA01]
Cellular Component: GO:0005737 - cytoplasm Inferred from experiment Inferred by computational analysis [UniProtGOA11, UniProtGOA11a, Powell78]
GO:0005829 - cytosol Inferred from experiment Inferred by computational analysis [DiazMejia09, Ishihama08, LopezCampistrou05]

MultiFun Terms: metabolism biosynthesis of building blocks amino acids leucine
metabolism biosynthesis of building blocks amino acids phenylalanine
metabolism biosynthesis of building blocks amino acids tyrosine

Essentiality data for tyrB knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB Lennox Yes 37 Aerobic 7   Yes [Baba06, Comment 1]
M9 medium with 1% glycerol Yes 37 Aerobic 7.2 0.35 Yes [Joyce06, Comment 2]
MOPS medium with 0.4% glucose Yes 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 1]
Yes [Feist07, Comment 3]

Credits:
Curated 13-Feb-2007 by Shearer A , SRI International
Curated 15-Jan-2010 by Fulcher C , SRI International
Last-Curated ? 17-Oct-2013 by Kubo A , SRI International


Enzymatic reaction of: aromatic-amino-acid transaminase (tyrosine aminotransferase)

EC Number: 2.6.1.57

an aromatic amino acid + 2-oxoglutarate <=> an aromatic oxo-acid + L-glutamate

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

This reaction is reversible.

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

Credits:
Imported from MetaCyc 24-May-2012 by Caspi R , SRI International


Enzymatic reaction of: leucine aminotransferase (tyrosine aminotransferase)

EC Number: 2.6.1.6/2.6.1.42

L-leucine + 2-oxoglutarate <=> 4-methyl-2-oxopentanoate + L-glutamate

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.

This reaction is reversible. [Powell78]

In Pathways: superpathway of leucine, valine, and isoleucine biosynthesis , leucine biosynthesis

Cofactors or Prosthetic Groups: pyridoxal 5'-phosphate [Powell78]

Inhibitors (Unknown Mechanism): L-tyrosine [Collier72] , L-leucine [Powell78a] , 3-methyl-2-oxobutanoate [Vartak91]

Primary Physiological Regulators of Enzyme Activity: L-tyrosine , L-leucine , 3-methyl-2-oxobutanoate


Enzymatic reaction of: tyrosine aminotransferase

Synonyms: aromatic-amino-acid transaminase, aromatic L-amino-acid transaminase, aromatic-amino-acid: 2-oxoglutarate aminotransferase, aromatic aminotransferase, aromatic amino acid aminotransferase

EC Number: 2.6.1.57

L-tyrosine + 2-oxoglutarate <=> 4-hydroxyphenylpyruvate + L-glutamate

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.

This reaction is reversible. [Powell78]

Alternative Substrates for L-tyrosine: L-aspartate

Alternative Substrates for 2-oxoglutarate: oxaloacetate

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

Summary:
Additional kinetic data pertaining to tyrosine, p-hydroxyphenylpyruvate, and oxaloacetate have been determined [Mavrides75, Gelfand77].

Cofactors or Prosthetic Groups: pyridoxal 5'-phosphate [Powell78]

Inhibitors (Unknown Mechanism): L-tyrosine [Collier72] , L-leucine [Powell78a] , 3-methyl-2-oxobutanoate [Vartak91]

Primary Physiological Regulators of Enzyme Activity: 3-methyl-2-oxobutanoate

Kinetic Parameters:

Substrate
Km (μM)
Citations
2-oxoglutarate
2500.0
[Mavrides75]
4-hydroxyphenylpyruvate
3900.0
[Gelfand77]
L-tyrosine
625.0
[Mavrides75]

pH(opt): 8 [Mavrides75]


Enzymatic reaction of: phenylalanine aminotransferase (tyrosine aminotransferase)

EC Number: 2.6.1.57

2-oxo-3-phenylpropanoate + L-glutamate <=> L-phenylalanine + 2-oxoglutarate

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

This reaction is reversible. [Powell78]

Alternative Substrates for L-phenylalanine: L-aspartate

Alternative Substrates for 2-oxoglutarate: oxaloacetate

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

Summary:
Additional kinetic data pertaining to phenylalanine, phenylpyruvate, and oxaloacetate have been determined [Mavrides75, Gelfand77].

Cofactors or Prosthetic Groups: pyridoxal 5'-phosphate [Powell78]

Inhibitors (Unknown Mechanism): L-tyrosine [Collier72] , L-leucine [Powell78a] , 3-methyl-2-oxobutanoate [Vartak91]

Primary Physiological Regulators of Enzyme Activity: 3-methyl-2-oxobutanoate

Kinetic Parameters:

Substrate
Km (μM)
Citations
2-oxo-3-phenylpropanoate
3900.0
[Gelfand77]
L-phenylalanine
333.0
[Mavrides75]

pH(opt): 7.5 [Mavrides75]


Sequence Features

Feature Class Location Citations Comment
Amino-Acid-Sites-That-Bind 34
[UniProt12]
UniProt: Substrate; via amide nitrogen; Non-Experimental Qualifier: by similarity.
Amino-Acid-Sites-That-Bind 66
[UniProt10a]
UniProt: Substrate; Non-Experimental Qualifier: by similarity;
Amino-Acid-Sites-That-Bind 131
[UniProt12]
UniProt: Substrate; Non-Experimental Qualifier: by similarity.
Amino-Acid-Sites-That-Bind 184
[UniProt12]
UniProt: Substrate; Non-Experimental Qualifier: by similarity.
N6-pyridoxal-phosphate-Lys-Modification 247
[UniProt11a]
UniProt: N6-(pyridoxal phosphate)lysine.
Amino-Acid-Sites-That-Bind 281
[UniProt10a]
UniProt: Substrate; Non-Experimental Qualifier: by similarity;
Amino-Acid-Sites-That-Bind 375
[UniProt12]
UniProt: Substrate; Non-Experimental Qualifier: by similarity.


Gene Local Context (not to scale): ?

Transcription Unit:

Notes:

History:
10/20/97 Gene b4054 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG11040; confirmed by SwissProt match.


References

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

Cho04: Cho BK, Park HY, Seo JH, Kinnera K, Lee BS, Kim BG (2004). "Enzymatic resolution for the preparation of enantiomerically enriched D-beta-heterocyclic alanine derivatives using Escherichia coli aromatic L-amino acid transaminase." Biotechnol Bioeng 88(4);512-9. PMID: 15459908

Collier72: Collier RH, Kohlhaw G (1972). "Nonidentity of the aspartate and the aromatic aminotransferase components of transaminase A in Escherichia coli." J Bacteriol 1972;112(1);365-71. PMID: 4404056

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

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

Fotheringham86: Fotheringham IG, Dacey SA, Taylor PP, Smith TJ, Hunter MG, Finlay ME, Primrose SB, Parker DM, Edwards RM (1986). "The cloning and sequence analysis of the aspC and tyrB genes from Escherichia coli K12. Comparison of the primary structures of the aspartate aminotransferase and aromatic aminotransferase of E. coli with those of the pig aspartate aminotransferase isoenzymes." Biochem J 1986;234(3);593-604. PMID: 3521591

Gelfand77: Gelfand DH, Steinberg RA (1977). "Escherichia coli mutants deficient in the aspartate and aromatic amino acid aminotransferases." J Bacteriol 1977;130(1);429-40. PMID: 15983

Gelfand77a: Gelfand DH, Rudo N (1977). "Mapping of the aspartate and aromatic amino acid aminotransferase genes tyrB and aspC." J Bacteriol 130(1);441-4. PMID: 323238

GOA01: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

Hayashi93: Hayashi H, Inoue K, Nagata T, Kuramitsu S, Kagamiyama H (1993). "Escherichia coli aromatic amino acid aminotransferase: characterization and comparison with aspartate aminotransferase." Biochemistry 32(45);12229-39. PMID: 8218300

Hayashi96: Hayashi H, Inoue K, Mizuguchi H, Kagamiyama H (1996). "Analysis of the substrate-recognition mode of aromatic amino acid aminotransferase by combined use of quasisubstrates and site-directed mutagenesis: systematic hydroxy-group addition/deletion studies to probe the enzyme-substrate interactions." Biochemistry 35(21);6754-61. PMID: 8639626

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

Islam00: Islam MM, Hayashi H, Mizuguchi H, Kagamiyama H (2000). "The substrate activation process in the catalytic reaction of Escherichia coli aromatic amino acid aminotransferase." Biochemistry 39(50);15418-28. PMID: 11112527

Iwasaki94: Iwasaki M, Hayashi H, Kagamiyama H (1994). "Protonation state of the active-site Schiff base of aromatic amino acid aminotransferase: modulation by binding of ligands and implications for its role in catalysis." J Biochem (Tokyo) 115(1);156-61. PMID: 8188625

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

Ko99: Ko TP, Wu SP, Yang WZ, Tsai H, Yuan HS (1999). "Crystallization and preliminary crystallographic analysis of the Escherichia coli tyrosine aminotransferase." Acta Crystallogr D Biol Crystallogr 55(Pt 8);1474-7. PMID: 10417420

Kuramitsu85a: Kuramitsu S, Inoue K, Ogawa T, Ogawa H, Kagamiyama H (1985). "Aromatic amino acid aminotransferase of Escherichia coli: nucleotide sequence of the tyrB gene." Biochem Biophys Res Commun 1985;133(1);134-9. PMID: 3907634

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

Mavrides75: Mavrides C, Orr W (1975). "Multispecific aspartate and aromatic amino acid aminotransferases in Escherichia coli." J Biol Chem 250(11);4128-33. PMID: 236311

Onuffer95: Onuffer JJ, Ton BT, Klement I, Kirsch JF (1995). "The use of natural and unnatural amino acid substrates to define the substrate specificity differences of Escherichia coli aspartate and tyrosine aminotransferases." Protein Sci 4(9);1743-9. PMID: 8528072

Powell78: Powell JT, Morrison JF (1978). "The purification and properties of the aspartate aminotransferase and aromatic-amino-acid aminotransferase from Escherichia coli." Eur J Biochem 1978;87(2);391-400. PMID: 352693

Powell78a: Powell JT, Morrison JF (1978). "Role of the Escherichia coli aromatic amino acid aminotransferase in leucine biosynthesis." J Bacteriol 136(1);1-4. PMID: 361681

UniProt10a: UniProt Consortium (2010). "UniProt version 2010-07 released on 2010-06-15 00:00:00." Database.

UniProt11a: UniProt Consortium (2011). "UniProt version 2011-11 released on 2011-11-22 00:00:00." Database.

UniProt12: UniProt Consortium (2012). "UniProt version 2012-11 released on 2012-11-26 00:00:00." Database.

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

UniProtGOA11a: 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."

Vartak91: Vartak NB, Liu L, Wang BM, Berg CM (1991). "A functional leuABCD operon is required for leucine synthesis by the tyrosine-repressible transaminase in Escherichia coli K-12." J Bacteriol 173(12);3864-71. PMID: 1646790

Yang87: Yang J, Pittard J (1987). "Molecular analysis of the regulatory region of the Escherichia coli K-12 tyrB gene." J Bacteriol 1987;169(10);4710-5. PMID: 3308851

Other References Related to Gene Regulation

Yang02: Yang J, Camakaris H, Pittard J (2002). "Molecular analysis of tyrosine-and phenylalanine-mediated repression of the tyrB promoter by the TyrR protein of Escherichia coli." Mol Microbiol 45(5);1407-19. PMID: 12207706


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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 Fri Dec 26, 2014, BIOCYC13A.