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Information on EC 4.1.2.48 - low-specificity L-threonine aldolase and Organism(s) Escherichia coli and UniProt Accession P75823
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4.1.2.48 low-specificity L-threonine aldolaseIUBMB Comments
Requires pyridoxal phosphate. The low-specificity L-threonine aldolase can act on both L-threonine and L-allo-threonine [1,2]. The enzyme from Escherichia coli can also act on L-threo-phenylserine and L-erythro-phenylserine . The enzyme can also catalyse the aldol condensation of glycolaldehyde and glycine to form 4-hydroxy-L-threonine, an intermediate of pyridoxal phosphate biosynthesis . Different from EC 4.1.2.5, L-threonine aldolase, and EC 4.1.2.49, L-allo-threonine aldolase.
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The taxonomic range for the selected organisms is: Escherichia coli
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
threonine aldolase, low-specificity l-threonine aldolase, serine hydroxy-methyl transferase, 
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topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
LtaE
LtaE
-
-
-
-
PATHWAY SOURCE
PATHWAYS
KEGG
-
-, -
SYSTEMATIC NAME
IUBMB Comments
L-threonine/L-allo-threonine acetaldehyde-lyase (glycine-forming)
Requires pyridoxal phosphate. The low-specificity L-threonine aldolase can act on both L-threonine and L-allo-threonine [1,2]. The enzyme from Escherichia coli can also act on L-threo-phenylserine and L-erythro-phenylserine [4]. The enzyme can also catalyse the aldol condensation of glycolaldehyde and glycine to form 4-hydroxy-L-threonine, an intermediate of pyridoxal phosphate biosynthesis [3]. Different from EC 4.1.2.5, L-threonine aldolase, and EC 4.1.2.49, L-allo-threonine aldolase.
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(R)-N-Cbz-alaninal + glycine
(2S,3R,4R)-2-amino-4-(benzyloxycarbonylamino)-3-hydroxypentanoic acid
-
conversion: 40%, glycine concentration: 70 mM, reaction temperature: 4°C, yield: 30%, L-erythro/L-threo: 16:84
-
-
?
(R)-N-Cbz-alaninal + glycine
(2S,3S,4R)-2-amino-4-(benzyloxycarbonylamino)-3-hydroxypentanoic acid
-
conversion: 40%, glycine concentration: 70 mM, reaction temperature: 4°C, yield: 30%, L-erythro/L-threo: 16:84
-
-
?
benzyloxyacetaldehyde + glycine
(2S,3R)-2-amino-4-(benzyloxy)-3-hydroxybutanoic acid
-
conversion: 45%, glycine concentration: 140 mM, reaction temperature: 25°C, yield: 30%, L-erythro/L-threo: 40:60
-
-
?
benzyloxyacetaldehyde + glycine
(2S,3S)-2-amino-4-(benzyloxy)-3-hydroxybutanoic acid
-
conversion: 45%, glycine concentration: 140 mM, reaction temperature: 25°C, yield: 30%, L-erythro/L-threo: 40:60
-
-
?
DL-threo-(3-methylsulfonylphenyl)serine
glycine + 3-methylsulfonylbenzaldehyde
121% of the activity with L-threonine
-
-
?
DL-threo-(3-nitrophenyl)serine
glycine + 3-nitrobenzaldehyde
143% of the activity with L-threonine
-
-
?
DL-threo-phenylserine
glycine + benzaldehyde
180% of the activity with L-threonine
-
-
?
glycine + glycolaldehyde
L-4-hydroxythreonine
-
low-specificity L-threonine aldolase is involved in a serendipitous pathway that converts 3-phosphohydroxypyruvate, an intermediate in the serine biosynthesis pathway, to L-4-phosphohydroxythreonine, an intermediate in the pyridoxal-5'-phosphate synthesis pathway in a strain of Escherichia coli that lacks 4-phosphoerythronate dehydrogenase
-
-
r
L-4-hydroxythreonine
glycine + glycolaldehyde
-
cleavage of L-4-hydroxythreonine is as efficient as cleavage of L-allo-threonine
-
-
r
N-(S)-benzyloxycarbonyl-alaninal + glycine
(2S,3R,4S)-2-amino-4-(benzyloxycarbonylamino)-3-hydroxypentanoic acid
-
conversion: 54%, glycine concentration: 140 mM, reaction temperature: 25°C, yield: 27%, L-erythro/L-threo: 18:82
-
-
?
N-(S)-benzyloxycarbonyl-alaninal + glycine
(2S,3S,4S)-2-amino-4-(benzyloxycarbonylamino)-3-hydroxypentanoic acid
-
conversion: 54%, glycine concentration: 140 mM, reaction temperature: 25°C, yield: 27%, L-erythro/L-threo: 18:82
-
-
?
N-benzyloxycarbonyl-3-aminopropanal + glycine
(2S,3R)-2-amino-5-(benzyloxycarbonylamino)-3-hydroxypentanoic acid
-
conversion: 49%, glycine concentration: 70 mM, reaction temperature: 25°C, yield: 11%, L-erythro/L-threo: 50:50
-
-
?
N-benzyloxycarbonyl-3-aminopropanal + glycine
(2S,3S)-2-amino-5-(benzyloxycarbonylamino)-3-hydroxypentanoic acid
-
conversion: 49%, glycine concentration: 70 mM, reaction temperature: 25°C, yield: 11%, L-erythro/L-threo: 50:50
-
-
?
N-benzyloxycarbonyl-glycinal + glycine
(2S,3R)-2-amino-4-(benzyloxycarbonylamino)-3-hydroxybutanoic acid
-
conversion: 60%, glycine concentration: 140 mM, reaction temperature: 25°C, yield: 18%, L-erythro/L-threo: 30:70
-
-
?
N-benzyloxycarbonyl-glycinal + glycine
(2S,3S)-2-amino-4-(benzyloxycarbonylamino)-3-hydroxybutanoic acid
-
conversion: 60%, glycine concentration: 140 mM, reaction temperature: 25°C, yield: 18%, L-erythro/L-threo: 30:70
-
-
?
L-allo-threonine
glycine + acetaldehyde
291% of the activity with L-threonine
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
glycine + glycolaldehyde
L-4-hydroxythreonine
-
low-specificity L-threonine aldolase is involved in a serendipitous pathway that converts 3-phosphohydroxypyruvate, an intermediate in the serine biosynthesis pathway, to L-4-phosphohydroxythreonine, an intermediate in the pyridoxal-5'-phosphate synthesis pathway in a strain of Escherichia coli that lacks 4-phosphoerythronate dehydrogenase
-
-
r
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
pyridoxal 5'-phosphate
contains 1 mol of pyridoxal 5'-phosphate as cofactor per mol of 36500 Da subunit
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
knockout of the ltaE gene of wild-type Escherichia coli does not affect the cellular growth rate, while disruption of the ltaE gene of Escherichia coli GS245, whose serine hydroxymethyltransferase gene is knocked out, causes a significant decrease in the cellular growth rate, suggesting that the threonine aldolase is not a major source of cellular glycine in wild-type Escherichia coli but catalyzes an alternative pathway for cellular glycine when serine hydroxymethyltransferase is inert
physiological function
threonine aldolase is not a major source of cellular glycine in wild-type Escherichia coli but catalyzes an alternative pathway for cellular glycine when serine hydroxymethyltransferase is inert
metabolism
-
reversible cleavage of L-3-hydroxy-alpha-amino acids to glycine and the corresponding aldehydes
physiological function
-
low-specificity L-threonine aldolase is involved in a serendipitous pathway that converts 3-phosphohydroxypyruvate, an intermediate in the serine biosynthesis pathway, to L-4-phosphohydroxythreonine, an intermediate in the pyridoxal-5'-phosphate synthesis pathway in a strain of Escherichia coli that lacks 4-phosphoerythronate dehydrogenase
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
the crystal structure of the low-specificity L-threonine aldolase is determined at 2.2 A resolution, in the unliganded form and co-crystallized with L-serine and L-threonine
at 2.2 A resolution, in the unliganded form and cocrystallized with L-serine and L-threonine. No active site catalytic residue is revealed, and a structural water molecule is assumed to act as the catalytic base in the retro-aldol cleavage reaction. The very large active site opening suggests that much larger molecules than L-threonine isomers may be easily accommodated
-
hanging drop vapor diffusion, low-pH crystal structure of the enzyme at 2.1 A resolution, with a noncovalently bound uncleaved L-serine substrate, and a pyridoxal 5'-phosphate cofactor bound as an internal aldimine. This structure contrasts with other Escherichia coli L-threonine aldolase structures obtained at physiological pH that show products or substrates bound as pyridoxal 5'-phosphate-external aldimines. The non-productive binding at low-pH is due to an unusual substrate serine binding orientation in which the alpha-amino group and carboxylate group are in the wrong positions (relative to the active site residues) as a result of protonation of the alpha-amino group of the serine, as well as the active site histidines, His83 and His126. Protonation of these residues prevent the characteristic nucleophilic attack of the alpha-amino group of substrate serine on C4' of pyridoxal 5'-phosphate to form the external aldimine. At low pH the change in charge distribution at the active site can result in substrates binding in a non-productive orientation
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
F87A
catalytic efficiency of the mutant enzyme for L-threonine is 1.7fold lower than that of the wild-type enzyme, catalytic efficiency of the mutant enzyme for L-allo-threonine is 1.2fold lower than that of the wild-type enzyme
F87D
catalytic efficiency of the mutant enzyme for L-threonine is 3.11fold lower than that of the wild-type enzyme, catalytic efficiency of the mutant enzyme for L-allo-threonine is 7.5fold lower than that of the wild-type enzyme
H83F/H126F
catalytic efficiency of the mutant enzyme for L-threonine is 3890fold lower than that of the wild-type enzyme, catalytic efficiency of the mutant enzyme for L-allo-threonine is 294fold lower than that of the wild-type enzyme
industry
biocatalysis using threonine aldolases opens up a way to synthesise beta-hydroxy-alpha-amino acids in one step. Dichiral beta-hydroxy-alpha-amino acids are a highly valuable class of compounds from which pharmaceutically active intermediates for the synthesis of e.g. beta-sympathomimetic drugs. Methods to immobilise the L-low specificity threonine aldolase of Escherichia coli are studied. The entrapment of the enzyme into a porous network of orthosilicate appears to be the most promising method
K222A
catalytic efficiency of the mutant enzyme for L-threonine is 13.4fold lower than that of the wild-type enzyme, catalytic efficiency of the mutant enzyme for L-allo-threonine is 9.7fold lower than that of the wild-type enzyme
synthesis
biocatalysis using threonine aldolases opens up a way to synthesise beta-hydroxy-alpha-amino acids in one step. Dichiral beta-hydroxy-alpha-amino acids are a highly valuable class of compounds from which pharmaceutically active intermediates for the synthesis of e.g. beta-sympathomimetic drugs. Methods to immobilise the L-low specificity threonine aldolase of Escherichia coli are studied. The entrapment of the enzyme into a porous network of orthosilicate appears to be the most promising method
F87A
-
no change in the ration of cleavage of L-threonine to L-allo-threonine
H126F
-
300% of wild-type activity,reduced preference for the erythro-substrate
H83F
-
less than 1% of wild-type activity, reduced preference for the erythro-substrate
H83F/H126F
-
able to catalyze the cleavage of both L-threonine and L-allo-threonine at a measurable rate, neither of the histidines acts as a catalytic base in the retro-aldol cleavage mechanism
K222A
-
slight decrease in kcat and slight increase in Km values for both L-threonine and L-allo-threonine
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
synthesis
the enzyme may be exploited for bioorganic synthesis of L-3-hydroxyamino acids that are biologically active or constitute building blocks for pharmaceutical molecules
pharmacology
-
biotechnological potential for the syntheses of pharmaceutically relevant drug molecules because of the stereospecificity
synthesis
synthesis of optically active beta-hydroxy-alpha-amino acids by immobilized Escherichia coli cells expressing the enzyme. The immobilized cells can be continuously used 10 times, yielding an average conversion rate of 60.4%
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Liu, J.Q.; Dairi, T.; Itoh, N.; Kataoka, M.; Shimizu, S.; Yamada, H.
Gene cloning, biochemical characterization and physiological role of a thermostable low-specificity L-threonine aldolase from Escherichia coli
Eur. J. Biochem.
255
220-226
1998
Escherichia coli (P75823), Escherichia coli
Gutierrez, M.L.; Garrabou, X.; Agosta, E.; Servi, S.; Parella, T.; Joglar, J.; Clapes, P.
Serine hydroxymethyl transferase from Streptococcus thermophilus and L-threonine aldolase from Escherichia coli as stereocomplementary biocatalysts for the synthesis of beta-hydroxy-alpha,omega-diamino acid derivatives
Chemistry
14
4647-4656
2008
Escherichia coli, Streptococcus thermophilus
Kim, J.; Kershner, J.P.; Novikov, Y.; Shoemaker, R.K.; Copley, S.D.
Three serendipitous pathways in E. coli can bypass a block in pyridoxal-5'-phosphate synthesis
Mol. Syst. Biol.
6
436
2010
Escherichia coli
Zhao, G.H.; Li, H.; Liu, W.; Zhang, W.G.; Zhang, F.; Liu, Q.; Jiao, Q.C.
Preparation of optically active beta-hydroxy-alpha-amino acid by immobilized Escherichia coli cells with serine hydroxymethyl transferase activity
Amino Acids
40
215-220
2011
Escherichia coli (P0A825), Escherichia coli
di Salvo, M.L.; Remesh, S.G.; Vivoli, M.; Ghatge, M.S.; Paiardini, A.; D'Aguanno, S.; Safo, M.K.; Contestabile, R.
On the catalytic mechanism and stereospecificity of Escherichia coli L-threonine aldolase
FEBS J.
281
129-145
2014
Escherichia coli, Escherichia coli WV_060327
Remesh, S.G.; Ghatge, M.S.; Ahmed, M.H.; Musayev, F.N.; Gandhi, A.; Chowdhury, N.; di Salvo, M.L.; Kellogg, G.E.; Contestabile, R.; Schirch, V.; Safo, M.K.
Molecular basis of E. coli L-threonine aldolase catalytic inactivation at low pH
Biochim. Biophys. Acta
1854
278-283
2015
Escherichia coli
Di Salvo, M.; Remesh, S.; Vivoli, M.; Ghatge, M.; Paiardini, A.; DAguanno, S.; Safo, M.; Contestabile, R.
On the catalytic mechanism and stereospecificity of Escherichia coli L-threonine aldolase
FEBS J.
281
129-145
2014
Escherichia coli (P75823)
Kurjatschij, S.; Katzberg, M.; Bertau, M.
Production and properties of threonine aldolase immobilisates
J. Mol. Catal. B
103
3-9
2014
Escherichia coli (P75823)
-
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