|Gene:||thrB||Accession Numbers: EG10999 (MetaCyc), b0003, ECK0003|
Species: Escherichia coli K-12 substr. MG1655
Subunit composition of homoserine kinase = [ThrB]2
Though it is a substrate, homoserine can actually cause partial inhibition of the reaction at higher concentrations, with a Ki of ~2 mM [Shames84a]. Substrate inhibition by high levels of ATP has also been observed [Chassagnole01]. ThrB has been subject to kinetic and mechanistic analysis [Shames84a, Huo96a]. The enzyme appears to have a second, regulatory binding site for L-homoserine [Shames84a, Chassagnole01]. Site-directed mutagenesis has confirmed the role of Arg234 and the His residues H139 and H205 in substrate binding [Huo96].
ThrB is required for growth of pdxB mutants on glucose and 3-hydroxyhomoserine or D-glycolaldehyde [Zhao96a]. Later, thrB was identified as a multicopy suppressor of the PLP auxotrophy of a pdxB deletion strain. ThrB was found to be part of a serendipitous metabolic pathway that produces an intermediate of the pyridoxal 5'-phosphate biosynthesis I pathway, 4-phospho-hydroxy-L-threonine, that lies downstream of PdxB [Kim10a]. The 4-hydroxy-L-threonine kinase activity of ThrB that is required for this pathway had already been identified in vitro [Shames84]. The pathway diverts 3-phosphohydroxypyruvate from serine biosynthesis [Kim10a].
Translation of ThrA and ThrB is coupled [Little89].
|Map Position: [2,801 -> 3,733]|
Molecular Weight of Polypeptide: 33.624 kD (from nucleotide sequence), 29 kD (experimental) [Burr76 ]
Molecular Weight of Multimer: 60.0 kD (experimental) [Burr76]
Unification Links: ASAP:ABE-0000010 , CGSC:110 , EchoBASE:EB0992 , EcoGene:EG10999 , EcoliWiki:b0003 , ModBase:P00547 , OU-Microarray:b0003 , PortEco:thrB , PR:PRO_000024067 , Pride:P00547 , Protein Model Portal:P00547 , RefSeq:NP_414544 , RegulonDB:EG10999 , SMR:P00547 , String:511145.b0003 , UniProt:P00547
Relationship Links: InterPro:IN-FAMILY:IPR000870 , InterPro:IN-FAMILY:IPR006203 , InterPro:IN-FAMILY:IPR006204 , InterPro:IN-FAMILY:IPR013750 , InterPro:IN-FAMILY:IPR014721 , InterPro:IN-FAMILY:IPR020568 , Pfam:IN-FAMILY:PF00288 , Pfam:IN-FAMILY:PF08544 , Prints:IN-FAMILY:PR00958 , Prosite:IN-FAMILY:PS00627
|Biological Process:||GO:0009088 - threonine biosynthetic process
[UniProtGOA12, UniProtGOA11a, GOA06, Theze74, Theze74a]
GO:0006566 - threonine metabolic process [GOA01a]
GO:0008652 - cellular amino acid biosynthetic process [UniProtGOA11a]
GO:0016310 - phosphorylation [UniProtGOA11a]
|Molecular Function:||GO:0004413 - homoserine kinase activity
[GOA06, GOA01, GOA01a, Burr76]
GO:0000166 - nucleotide binding [UniProtGOA11a]
GO:0005524 - ATP binding [UniProtGOA11a, GOA06, GOA01a]
GO:0016301 - kinase activity [UniProtGOA11a]
GO:0016740 - transferase activity [UniProtGOA11a]
|Cellular Component:||GO:0005829 - cytosol
[DiazMejia09, Ishihama08, LopezCampistrou05]
GO:0005737 - cytoplasm [UniProtGOA11, UniProtGOA11a, GOA06]
|MultiFun Terms:||metabolism → biosynthesis of building blocks → amino acids → threonine|
Enzymatic reaction of: homoserine kinase
Synonyms: ATP:L-homoserine O-phosphotransferase
EC Number: 22.214.171.124
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. [Burr76]
In Pathways: superpathway of L-isoleucine biosynthesis I , superpathway of L-threonine biosynthesis , superpathway of L-lysine, L-threonine and L-methionine biosynthesis I , aspartate superpathway , L-threonine biosynthesis
Cofactor Binding Comment: Mg facilitates binding of homoserine
Inhibitors (Competitive): 2-aminobutanoate [Theze74b, Burr76] , 2-chloro-L-alanine [Theze74b, Burr76] , L-cysteine [Theze74b, Burr76, Comment 1] , L-homocysteine [Theze74b, Burr76, Comment 1] , L-threonine [Theze74b, Burr76, Comment 1]
Primary Physiological Regulators of Enzyme Activity: L-threonine
pH(opt): 7.8 [Theze74b]
Enzymatic reaction of: 4-hydroxythreonine kinase (homoserine kinase)
EC Number: 2.7.1.-
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.
The reaction is physiologically favored in the direction shown.
|Nucleotide-Phosphate-Binding-Region||91 -> 101|
10/20/97 Gene b0003 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10999; confirmed by SwissProt match.
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
Kim10a: Kim J, Kershner JP, Novikov Y, Shoemaker RK, Copley SD (2010). "Three serendipitous pathways in E. coli can bypass a block in pyridoxal-5'-phosphate synthesis." Mol Syst Biol 6;436. PMID: 21119630
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
Shames84: Shames SL, Ash DE, Wedler FC, Villafranca JJ (1984). "Interaction of aspartate and aspartate-derived antimetabolites with the enzymes of the threonine biosynthetic pathway of Escherichia coli." J Biol Chem 1984;259:15331-15339. PMID: 6150934
Theze74a: Theze J, Margarita D, Cohen GN, Borne F, Patte JC (1974). "Mapping of the structural genes of the three aspartokinases and of the two homoserine dehydrogenases of Escherichia coli K-12." J Bacteriol 117(1);133-43. PMID: 4148765
Theze74b: Theze J, Kleidman L, St Girons I (1974). "Homoserine kinase from Escherichia coli K-12: properties, inhibition by L-threonine, and regulation of biosynthesis." J Bacteriol 1974;118(2);577-81. PMID: 4364023
Zhao96a: Zhao G, Winkler ME (1996). "4-Phospho-hydroxy-L-threonine is an obligatory intermediate in pyridoxal 5'-phosphate coenzyme biosynthesis in Escherichia coli K-12." FEMS Microbiol Lett 1996;135(2-3);275-80. PMID: 8595869
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