MetaCyc Enzyme: threonine deaminase

Gene: ilvA Accession Numbers: EG10493 (MetaCyc), b3772, ECK3764

Synonyms: ile, threonine dehydratase

Species: Escherichia coli K-12 substr. MG1655

Subunit composition of threonine deaminase = [IlvA]4

Threonine deaminase (IlvA) carries out the first step in the synthesis of isoleucine. IlvA catalyzes the breakdown of L-threonine to generate 2-oxobutanoate and ammonia [Umbarger56, Umbarger57, Ramakrishnan64, Ramakrishnan65, Ramakrishnan65a]. Although the conversion of threonine into oxobutanoate is also the first step in the pathway of threonine degradation, IlvA is not thought to play a role in that pathway. This expectation is bolstered by the presence of an oxygen-responsive promoter for ilvA and the anaerobic nature of the degradation pathway.

Threonine deaminase is a tetramer [Grimminger73]. It has been alternately reported that either two or four pyridoxal phosphate molecules bind per tetramer [Koerner75, Eisenstein91]. In the complete absence of pyridoxal phosphate, the enzyme dissociates into nonfunctional 102 kD dimers [Calhoun73]. It has also been suggested that IlvA has several active multimeric forms, rather than being solely active as a tetramer [Kagan75]. The regulatory small molecules valine and isoleucine both bind threonine deaminase at four molecules per tetramer, the former cooperatively [Eisenstein94]. Isoleucine binds only twice per tetramer [Koerner75]. Crystal structures of threonine deaminase to 2.8 and 2.9 Å resolution reveal that it is a dimer of dimers, consisting of a set of carboxy-terminal regulatory domains projecting outward from a core of pyridoxal-containing amino-termini [Gallagher98, Gallagher98a]. The regulatory domains possessed two effector-binding sites [Chen13].

Valine and isoleucine work to promote states with high and low affinity, respectively, for threonine. Isoleucine also appears to directly impact catalysis [Eisenstein95].

IlvA is cotranslated with IlvD [Harms88]. In addition to this contranslation, ilvA can also be transcribed and translated separately from its own oxygen-sensitive promoter [Lopes89].

IlvA abundance increases following treatment of cells with glycyl-leucine [Vonder72].

Mutations in ilvA code for enzymes with significantly reduced threonine deaminase activity, while overexpression of threonine demaminase resulted in growth inhibition most likely due to accumulation of toxic levels of α-ketobutyrate [Fisher93]. Inhibition of threonine demaminase is involved in homocysteine toxicity [Tuite05].

Locations: cytosol

Map Position: [3,953,354 -> 3,954,898]

Molecular Weight of Polypeptide: 56.195 kD (from nucleotide sequence)

pI: 6.04

Unification Links: ASAP:ABE-0012321 , CGSC:609 , DIP:DIP-10018N , EchoBASE:EB0488 , EcoGene:EG10493 , EcoliWiki:b3772 , Mint:MINT-1305200 , ModBase:P04968 , OU-Microarray:b3772 , PortEco:ilvA , PR:PRO_000023001 , Pride:P04968 , Protein Model Portal:P04968 , RefSeq:NP_418220 , RegulonDB:EG10493 , SMR:P04968 , String:511145.b3772 , UniProt:P04968

Relationship Links: InterPro:IN-FAMILY:IPR000634 , InterPro:IN-FAMILY:IPR001721 , InterPro:IN-FAMILY:IPR001926 , InterPro:IN-FAMILY:IPR005787 , PDB:Structure:1TDJ , Pfam:IN-FAMILY:PF00291 , Pfam:IN-FAMILY:PF00585 , Prosite:IN-FAMILY:PS00165 , Prosite:IN-FAMILY:PS51672

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

GO Terms:

Biological Process: GO:0006566 - threonine metabolic process Inferred from experiment [Umbarger57]
GO:0009082 - branched-chain amino acid biosynthetic process Inferred from experiment Inferred by computational analysis [UniProtGOA11, Williams78]
GO:0009097 - isoleucine biosynthetic process Inferred from experiment Inferred by computational analysis [UniProtGOA12, UniProtGOA11, GOA01, Fisher93, Favre74, Calhoun73]
GO:0006520 - cellular amino acid metabolic process Inferred by computational analysis [GOA01]
GO:0008152 - metabolic process Inferred by computational analysis [UniProtGOA11]
GO:0008652 - cellular amino acid biosynthetic process Inferred by computational analysis [UniProtGOA11]
Molecular Function: GO:0004794 - L-threonine ammonia-lyase activity Inferred from experiment Inferred by computational analysis [GOA01a, GOA01, Fisher93, Favre74, Eisenstein91, Calhoun73]
GO:0016597 - amino acid binding Inferred from experiment [Eisenstein91]
GO:0030170 - pyridoxal phosphate binding Inferred from experiment Inferred by computational analysis [GOA01, Eisenstein91]
GO:0003824 - catalytic activity Inferred by computational analysis [UniProtGOA11]
GO:0016829 - lyase activity Inferred by computational analysis [UniProtGOA11]
Cellular Component: GO:0005737 - cytoplasm Inferred by computational analysis [Gaudet10]
GO:0005829 - cytosol Inferred by computational analysis [DiazMejia09]

MultiFun Terms: metabolism biosynthesis of building blocks amino acids isoleucine/valine

Imported from EcoCyc 27-Jan-2015 by Paley S , SRI International

Enzymatic reaction of: threonine deaminase

Synonyms: L-threonine hydro-lyase (deaminating), threonine dehydratase

L-threonine <=> (2Z)-2-aminobut-2-enoate + H2O + H+

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

The reaction is irreversible in the direction shown.

In Pathways: superpathway of L-isoleucine biosynthesis I , superpathway of L-threonine metabolism , superpathway of branched amino acid biosynthesis , L-isoleucine biosynthesis I (from threonine)

Imported from EcoCyc 27-Jan-2015 by Paley S , SRI International

Inhibition by cysteine is partially competitive with respect to threonine [Harris81].

Cofactors or Prosthetic Groups: pyridoxal 5'-phosphate [Umbarger57, Umbarger56, Eisenstein91]

Activators (Unknown Mechanism): L-valine [Squires81]

Inhibitors (Other): L-cysteine [Harris81]

Inhibitors (Unknown Mechanism): D-cysteine [Soutourina01] , isoleucine tetrazole [Willshaw75] , L-isoleucine [Vonder72, Umbarger57, Umbarger56] , L-leucine [Vonder72]

Primary Physiological Regulators of Enzyme Activity: L-cysteine , L-isoleucine , L-leucine , L-valine

Kinetic Parameters:

Km (μM)

pH(opt): 8-10 [Calhoun73]

Sequence Features

Feature Class Location Citations Comment
N6-pyridoxal-phosphate-Lys-Modification 62
UniProt: N6-(pyridoxal phosphate)lysine.
Amino-Acid-Sites-That-Bind 89
UniProt: Pyridoxal phosphate.
Sequence-Conflict 120
[Garrison86, UniProt10a]
UniProt: (in Ref. 2);
Sequence-Conflict 140
[Garrison86, UniProt10a]
UniProt: (in Ref. 2; AAA24014/AAA67575);
Protein-Segment 189 -> 192
UniProt: Pyridoxal phosphate binding; Sequence Annotation Type: region of interest.
Sequence-Conflict 195
[Garrison86, UniProt10a]
UniProt: (in Ref. 2; AAA24014);
Sequence-Conflict 243
[Lawther87, UniProt10a]
UniProt: (in Ref. 3; AAA24024);
Amino-Acid-Sites-That-Bind 315
UniProt: Pyridoxal phosphate.
Sequence-Conflict 334
[Garrison86, UniProt10a]
UniProt: (in Ref. 2; AAA24014);
Conserved-Region 339 -> 411
UniProt: ACT-like 1.
Conserved-Region 434 -> 504
UniProt: ACT-like 2.

10/20/97 Gene b3772 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10493; confirmed by SwissProt match.


Calhoun73: Calhoun DH, Rimerman RA, Hatfield GW (1973). "Threonine deaminase from Escherichia coli. I. Purification and properties." J Biol Chem 1973;248(10);3511-6. PMID: 4573981

Chen13: Chen L, Chen Z, Zheng P, Sun J, Zeng AP (2013). "Study and reengineering of the binding sites and allosteric regulation of biosynthetic threonine deaminase by isoleucine and valine in Escherichia coli." Appl Microbiol Biotechnol 97(7);2939-49. PMID: 22669632

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

Eisenstein91: Eisenstein E (1991). "Cloning, expression, purification, and characterization of biosynthetic threonine deaminase from Escherichia coli." J Biol Chem 1991;266(9);5801-7. PMID: 2005118

Eisenstein94: Eisenstein E, Yu HD, Schwarz FP (1994). "Cooperative binding of the feedback modifiers isoleucine and valine to biosynthetic threonine deaminase from Escherichia coli." J Biol Chem 269(47);29423-9. PMID: 7961922

Eisenstein95: Eisenstein E (1995). "Allosteric regulation of biosynthetic threonine deaminase from Escherichia coli: effects of isoleucine and valine on active-site ligand binding and catalysis." Arch Biochem Biophys 316(1);311-8. PMID: 7840631

Favre74: Favre R, Iaccarino M, Levinthal M (1974). "Complementation between different mutations in the ilvA gene of Escherichia coli K-12." J Bacteriol 119(3);1069-71. PMID: 4604254

Fisher93: Fisher KE, Eisenstein E (1993). "An efficient approach to identify ilvA mutations reveals an amino-terminal catalytic domain in biosynthetic threonine deaminase from Escherichia coli." J Bacteriol 175(20);6605-13. PMID: 8407838

Gallagher98: Gallagher DT, Gilliland GL, Xiao G, Zondlo J, Fisher KE, Chinchilla D, Eisenstein E (1998). "Structure and control of pyridoxal phosphate dependent allosteric threonine deaminase." Structure 6(4);465-75. PMID: 9562556

Gallagher98a: Gallagher DT, Eisenstein E, Fisher KE, Zondlo J, Chinchilla D, Yu HD, Dill J, Winborne E, Ducote K, Xiao G, Gilliland GL (1998). "Polymorphous crystallization and diffraction of threonine deaminase from Escherichia coli." Acta Crystallogr D Biol Crystallogr 54(Pt 3);467-9. PMID: 9761930

Garrison86: Garrison E., Harms E., Umbarger H.E. (1986). Data submission to EMBL/GenBank/DDBJ databases on 1986-08.

Gaudet10: Gaudet P, Livstone M, Thomas P (2010). "Annotation inferences using phylogenetic trees." PMID: 19578431

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.

Grimminger73: Grimminger H, Rahimi-Laridjani I, Koerner K, Lingens F (1973). "Purification of threonine deaminase from Escherichia coli." FEBS Lett 35(2);273-5. PMID: 4582943

Harms88: Harms E, Higgins E, Chen JW, Umbarger HE (1988). "Translational coupling between the ilvD and ilvA genes of Escherichia coli." J Bacteriol 170(10);4798-807. PMID: 3049548

Harris81: Harris CL (1981). "Cysteine and growth inhibition of Escherichia coli: threonine deaminase as the target enzyme." J Bacteriol 145(2);1031-5. PMID: 7007336

Kagan75: Kagan ZS, Dorozhko AI, Kovaleva SV, Yakovleva LI (1975). "Studies of homogeneous "biosynthetic" L-threonine dehydratase from Escherichia coli K-12. Some kinetic properties and molecular multiplicity." Biochim Biophys Acta 403(1);208-20. PMID: 240428

Koerner75: Koerner K, Rahimi-Laridjani I, Grimminger H (1975). "Purification of biosynthetic threonine deaminase from Escherichia coli." Biochim Biophys Acta 397(1);220-30. PMID: 1096954

Lawther87: Lawther RP, Wek RC, Lopes JM, Pereira R, Taillon BE, Hatfield GW (1987). "The complete nucleotide sequence of the ilvGMEDA operon of Escherichia coli K-12." Nucleic Acids Res 1987;15(5);2137-55. PMID: 3550695

Lopes89: Lopes JM, Lawther RP (1989). "Physical identification of an internal promoter, ilvAp, in the distal portion of the ilvGMEDA operon." Gene 76(2);255-69. PMID: 2473940

Ramakrishnan64: Ramakrishnan T, Adelberg EA (1964). "Regulatory mechanisms in the biosynthesis of isoleucine and valine. I. Genetic derepression of enzyme formation." J Bacteriol 87;566-73. PMID: 14127571

Ramakrishnan65: Ramakrishnan T, Adelberg EA (1965). "Regulatory mechanisms in the biosynthesis of isoleucine and valine. II. Identification of two operator genes." J Bacteriol 89;654-60. PMID: 14273640

Ramakrishnan65a: Ramakrishnan T, Adelberg EA (1965). "Regulatory mechanisms in the biosynthesis of isoleucine and valine. 3. Map order of the structural genes and operator genes." J Bacteriol 89;661-4. PMID: 14273641

Soutourina01: Soutourina J, Blanquet S, Plateau P (2001). "Role of D-cysteine desulfhydrase in the adaptation of Escherichia coli to D-cysteine." J Biol Chem 276(44);40864-72. PMID: 11527960

Squires81: Squires CH, Levinthal M, De Felice M (1981). "A role for threonine deaminase in the regulation of alpha-acetolactate biosynthesis in Escherichia coli K12." J Gen Microbiol 1981;127, pt 1;19-25. PMID: 7040602

Tuite05: Tuite NL, Fraser KR, O'byrne CP (2005). "Homocysteine toxicity in Escherichia coli is caused by a perturbation of branched-chain amino acid biosynthesis." J Bacteriol 187(13);4362-71. PMID: 15968045

Umbarger56: Umbarger HE, Brown B (1956). "Threonine deamination in Escherichia coli. I. D- and L-threonine deaminase activities of cell-free extracts." J Bacteriol 71(4);443-9. PMID: 13319259

Umbarger57: Umbarger HE, Brown B (1957). "Threonine deamination in Escherichia coli. II. Evidence for two L-threonine deaminases." J Bacteriol 73(1);105-12. PMID: 13405870

UniProt10a: UniProt Consortium (2010). "UniProt version 2010-11 released on 2010-11-02 00:00:00." Database.

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

UniProt12b: UniProt Consortium (2012). "UniProt version 2012-09 released on 2012-09-12 00:00:00." Database.

UniProt13: UniProt Consortium (2013). "UniProt version 2013-08 released on 2013-08-01 00:00:00." Database.

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."

Vonder72: Vonder Haar RA, Umbarger HE (1972). "Isoleucine and valine metabolism in Escherichia coli. XIX. Inhibition of isoleucine biosynthesis by glycyl-leucine." J Bacteriol 112(1);142-7. PMID: 4562390

Williams78: Williams AL, Whitfield SM, Williams LS (1978). "Synthesis and activities of branched-chain aminoacyl-tRNA synthetases in threonine deaminase mutants of Escherichia coli." J Bacteriol 134(1);92-9. PMID: 348689

Willshaw75: Willshaw GA, Tristram H (1975). "Inhibition of Escherichia coli isoleucine biosynthesis by isoleucine tetrazole." J Bacteriol 123(3);862-70. PMID: 1099080

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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