|Gene:||tdh||Accession Numbers: EG10993 (MetaCyc), b3616, ECK3606|
Species: Escherichia coli K-12 substr. MG1655
Subunit composition of threonine dehydrogenase = [Tdh]4
Threonine dehydrogenase (Tdh) catalyzes the conversion of L-threonine to the unstable intermediate L-2-amino-3-oxobutanoate, which can spontaneously decarboxylate yielding aminoacetone and CO2 or be converted to acetyl-CoA and glycine by the second enzyme in the catabolic pathway. This is the major catabolic pathway for threonine utilization. This two step pathway also provides an alternative route for glycine and serine biosynthesis in E. coli. [Craig90, Epperly91, Aronson89, Boylan81]
Tdh is a member of the zinc-containing long-chain alcohol/polyol dehydrogenase family [Aronson89, Epperly91]. The enzyme is damaged by micromolar concentrations of hydrogen peroxide in vitro due to oxidation of the cysteine residue [Anjem12].
Inactivation studies of Tdh have provided evidence for a catalytically essential arginine residue [Epperly89] as well as active site cysteine [Epperly91] and histidine [Marcus95] residues. Mutant studies have also identified functionally important residues [Chen95] including His-90 [Johnson98a], and a possible catalytic zinc binding site at Cys-38 [Johnson98b].
Review: Reitzer, L. (2005) "Catabolism of Amino Acids and Related Compounds" EcoSal 3.4.7 [ECOSAL]
|Map Position: [3,788,343 <- 3,789,368]|
Molecular Weight of Polypeptide: 37.239 kD (from nucleotide sequence), 35.0 kD (experimental) [Boylan81 ]
Molecular Weight of Multimer: 140.0 kD (experimental) [Boylan81]
Unification Links: ASAP:ABE-0011830 , CGSC:17584 , DIP:DIP-6855N , EchoBASE:EB0986 , EcoGene:EG10993 , EcoliWiki:b3616 , ModBase:P07913 , OU-Microarray:b3616 , PortEco:tdh , PR:PRO_000024044 , Pride:P07913 , Protein Model Portal:P07913 , RefSeq:NP_418073 , RegulonDB:EG10993 , SMR:P07913 , String:511145.b3616 , UniProt:P07913
Relationship Links: InterPro:IN-FAMILY:IPR002085 , InterPro:IN-FAMILY:IPR002328 , InterPro:IN-FAMILY:IPR004627 , InterPro:IN-FAMILY:IPR011032 , InterPro:IN-FAMILY:IPR013149 , InterPro:IN-FAMILY:IPR013154 , InterPro:IN-FAMILY:IPR016040 , Panther:IN-FAMILY:PTHR11695 , Pfam:IN-FAMILY:PF00107 , Pfam:IN-FAMILY:PF08240 , Prosite:IN-FAMILY:PS00059
|Biological Process:||GO:0006564 - L-serine biosynthetic process
GO:0006567 - threonine catabolic process [GOA06, GOA01a, Chen95]
GO:0019518 - L-threonine catabolic process to glycine [UniProtGOA12]
GO:0055114 - oxidation-reduction process [UniProtGOA11a, GOA01a]
|Molecular Function:||GO:0008198 - ferrous iron binding
GO:0008270 - zinc ion binding [GOA06, GOA01a, Epperly91]
GO:0008743 - L-threonine 3-dehydrogenase activity [GOA06, GOA01, GOA01a, Anjem12, Boylan81]
GO:0016491 - oxidoreductase activity [UniProtGOA11a, GOA01a, Boylan81]
GO:0030145 - manganese ion binding [Boylan81, Craig86]
GO:0042802 - identical protein binding [Boylan81]
GO:0046870 - cadmium ion binding [Craig88]
GO:0046872 - metal ion binding [UniProtGOA11a]
|Cellular Component:||GO:0005737 - cytoplasm
[UniProtGOA11, UniProtGOA11a, GOA06, Boylan81]
GO:0005829 - cytosol [DiazMejia09, Ishihama08, Lasserre06]
|MultiFun Terms:||metabolism → carbon utilization → amino acids|
|metabolism → central intermediary metabolism → threonine catabolism|
Enzymatic reaction of: threonine dehydrogenase
Synonyms: threonine 3-dehydrogenase, L-threonine 3-dehydrogenase, L-threonine:NAD+ oxidoreductase
EC Number: 188.8.131.52
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 favored in the direction shown.
The enzyme was specific for NAD+ although it could also utilize several analogs of NAD+. NADP+ was inactive as a cofactor [Boylan81].
Inhibitors (Unknown Mechanism): cyclohexane-1,2-dione [Epperly89] , Cu2+ [Boylan81, Craig86] , Ni2+ [Boylan81, Craig86] , Be2+ [Craig86] , Hg2+ [Craig86] , Ag2+ [Craig86] , p-mercuribenzoate [Boylan81] , 5,5'-dithio-bis-2-nitrobenzoate [Boylan81] , 2-mercaptoethanol [Comment 3] , diacetyl [Epperly89] , phenylglyoxal [Epperly89] , 2,3-pentane-dione [Epperly89]
Primary Physiological Regulators of Enzyme Activity: diacetyl
pH(opt): 10.3 [Boylan81]
10/20/97 Gene b3616 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10993; confirmed by SwissProt match.
Chen95: Chen YW, Dekker EE, Somerville RL (1995). "Functional analysis of E. coli threonine dehydrogenase by means of mutant isolation and characterization." Biochim Biophys Acta 1253(2);208-14. PMID: 8519804
Craig90: Craig PA, Dekker EE (1990). "The sulfhydryl content of L-threonine dehydrogenase from Escherichia coli K-12: relation to catalytic activity and Mn2+ activation." Biochim Biophys Acta 1990;1037(1);30-8. PMID: 2104757
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
Epperly89: Epperly BR, Dekker EE (1989). "Inactivation of Escherichia coli L-threonine dehydrogenase by 2,3-butanedione. Evidence for a catalytically essential arginine residue." J Biol Chem 1989;264(31);18296-301. PMID: 2681195
Epperly91: Epperly BR, Dekker EE (1991). "L-threonine dehydrogenase from Escherichia coli. Identification of an active site cysteine residue and metal ion studies." J Biol Chem 1991;266(10);6086-92. PMID: 2007567
Johnson98a: Johnson AR, Dekker EE (1998). "Site-directed mutagenesis of histidine-90 in Escherichia coli L-threonine dehydrogenase alters its substrate specificity." Arch Biochem Biophys 351(1);8-16. PMID: 9500838
Johnson98b: Johnson AR, Chen YW, Dekker EE (1998). "Investigation of a catalytic zinc binding site in Escherichia coli L-threonine dehydrogenase by site-directed mutagenesis of cysteine-38." Arch Biochem Biophys 358(2);211-21. PMID: 9784233
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
Marcus95: Marcus JP, Dekker EE (1995). "Identification of a second active site residue in Escherichia coli L-threonine dehydrogenase: methylation of histidine-90 with methyl p-nitrobenzenesulfonate." Arch Biochem Biophys 316(1);413-20. PMID: 7840645
©2014 SRI International, 333 Ravenswood Avenue, Menlo Park, CA 94025-3493