Information on EC 1.1.1.3 - homoserine dehydrogenase

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria

EC NUMBER
COMMENTARY
1.1.1.3
-
RECOMMENDED NAME
GeneOntology No.
homoserine dehydrogenase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
L-homoserine + NAD(P)+ = L-aspartate 4-semialdehyde + NAD(P)H + H+
show the reaction diagram
-
-
-
-
L-homoserine + NAD(P)+ = L-aspartate 4-semialdehyde + NAD(P)H + H+
show the reaction diagram
bifunctional enzyme showing aspartate kinase, 2.7.2.4, and homoserine dehydrogenase activities
-
L-homoserine + NAD(P)+ = L-aspartate 4-semialdehyde + NAD(P)H + H+
show the reaction diagram
bifunctional enzyme showing aspartate kinase, EC 2.7.2.4, and homoserine dehydrogenase activities
-
L-homoserine + NAD(P)+ = L-aspartate 4-semialdehyde + NAD(P)H + H+
show the reaction diagram
bifunctional enzyme showing aspartate kinase, EC 2.7.2.4, and homoserine dehydrogenase activities
-
L-homoserine + NAD(P)+ = L-aspartate 4-semialdehyde + NAD(P)H + H+
show the reaction diagram
ordered bi bi kinetic mechanism in which nicotinamide cofactor binds first and leaves last in the reaction sequence
O63067, O65027, Q3S3F6
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Biosynthesis of antibiotics
-
-
Biosynthesis of secondary metabolites
-
-
Cysteine and methionine metabolism
-
-
Glycine, serine and threonine metabolism
-
-
L-homoserine biosynthesis
-
-
Lysine biosynthesis
-
-
Metabolic pathways
-
-
Microbial metabolism in diverse environments
-
-
threonine metabolism
-
-
SYSTEMATIC NAME
IUBMB Comments
L-homoserine:NAD(P)+ oxidoreductase
The yeast enzyme acts most rapidly with NAD+; the Neurospora enzyme with NADP+. The enzyme from Escherichia coli is a multi-functional protein, which also catalyses the reaction of EC 2.7.2.4 (aspartate kinase).
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
AK-HSD-1
O63067, O65027
-
AK-HSDH
-
isoform 1, bifunctional enzyme EC 2.7.2.4/EC 1.1.1.3
AK-HSDH
O81852
-
aspartate kinase-homoserine dehydrogenase
-
-
aspartate kinase-homoserine dehydrogenase
-
bifunctional enzyme EC 2.7.2.4/EC 1.1.1.3
aspartate kinase-homoserine dehydrogenase
O81852
-
aspartokinase-homoserine dehydrogenase I
-
-
HDH
-
-
-
-
hom-1
D8WXQ1, D8WXQ2
-
hom-1
D8WXQ1, D8WXQ2
-
-
homoserine dehydrogenase 1
-
-
homoserine dehydrogenase 1
Lactobacillus plantarum NCIMB 8826
-
-
-
homoserine dehydrogenase 2
-
-
homoserine dehydrogenase 2
Lactobacillus plantarum NCIMB 8826
-
-
-
HSD
-
-
-
-
HSDH
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9028-13-1
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
bifunctional enzyme showing aspartate dehydrogenase and aspartate kinase activity
-
-
Manually annotated by BRENDA team
slightly modified at base 60 c to t, bas 1242 t to g, and base 1403 t to c, the latter modification results in change of Leu468 to Ser; var. Columbia, bifunctional enzyme showing aspartate dehydrogenase and aspartate kinase activity
TREMBL
Manually annotated by BRENDA team
var. Bensheim showing threonine and methionine prototrophy, bifunctional enzyme showing aspartate dehydrogenase and aspartate kinase activity, gene akthr2
-
-
Manually annotated by BRENDA team
isoform hom-1
UniProt
Manually annotated by BRENDA team
isoform hom-2
UniProt
Manually annotated by BRENDA team
isoform hom-1
UniProt
Manually annotated by BRENDA team
isoform hom-2
UniProt
Manually annotated by BRENDA team
two isozymes
-
-
Manually annotated by BRENDA team
a methionine-producing strain carrying mutations in the hom and the thrB genes
-
-
Manually annotated by BRENDA team
bifunctional aspartokinase-homoserine dehydrogenase AK-HSD-1
UniProt
Manually annotated by BRENDA team
bifunctional aspartokinase-homoserine dehydrogenase AK-HSD-2
UniProt
Manually annotated by BRENDA team
barley
-
-
Manually annotated by BRENDA team
castor bean
-
-
Manually annotated by BRENDA team
mutant strain M20-20D and wild-type strain S2207A
-
-
Manually annotated by BRENDA team
also shows aspartase kinase activity
-
-
Manually annotated by BRENDA team
also shows aspartase kinase activity; spinach
-
-
Manually annotated by BRENDA team
strain NRRL 3585, gene hom
UniProt
Manually annotated by BRENDA team
Streptomyces clavuligerus NRRL 3585
strain NRRL 3585, gene hom
UniProt
Manually annotated by BRENDA team
Thermophilic bacterium
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
D8WXQ1, D8WXQ2
contrary to wild-type MGA3 cells that secrete 0.4 g/l L-lysine and 59 g/l L-glutamate under optimised fed batch methanol fermentation, the hom-1 mutant M168-20 secretes 11 g/l L-lysine and 69 g/l of L-glutamate. Overproduction of pyruvate carboxylase and its mutant enzyme P455S in M168-20 has no positive effect on the volumetric L-lysine yield and the L-lysine yield on methanol, and causes significantly reduced volumetric L-glutamate yield and L-glutamate yield on methanol
physiological function
-
contrary to wild-type MGA3 cells that secrete 0.4 g/l L-lysine and 59 g/l L-glutamate under optimised fed batch methanol fermentation, the hom-1 mutant M168-20 secretes 11 g/l L-lysine and 69 g/l of L-glutamate. Overproduction of pyruvate carboxylase and its mutant enzyme P455S in M168-20 has no positive effect on the volumetric L-lysine yield and the L-lysine yield on methanol, and causes significantly reduced volumetric L-glutamate yield and L-glutamate yield on methanol
-
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
show the reaction diagram
-
-
-
r
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
show the reaction diagram
-
-
-
r
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
show the reaction diagram
-
-
-
r
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
show the reaction diagram
-
-
-
r
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
show the reaction diagram
P31116
-
-
-
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
show the reaction diagram
-
-
-
-
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
show the reaction diagram
-
-
-
-
?
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
show the reaction diagram
-
-
-
r
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
show the reaction diagram
-
-
-
-
r
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
show the reaction diagram
-
-
-
r
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
show the reaction diagram
-
-
-
r
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
show the reaction diagram
-
-
-
r
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
show the reaction diagram
-
-
-
r
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
show the reaction diagram
-
-
-
r
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
show the reaction diagram
-
-
-
r
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
show the reaction diagram
-
-
-
r
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
show the reaction diagram
Thermophilic bacterium
-
-
-
r
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
show the reaction diagram
-
kinetic mechanism
-
-
r
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
show the reaction diagram
-
kinetic mechanism
-
-
r
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
show the reaction diagram
-
third reaction in the pathway between aspartate and the amino acids threonine, isoleucine, methionine
-
-
r
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
show the reaction diagram
-
essential step in amino acids L-methionine, L-threonine, and L-isoleucine biosynthesis
-
-
?
L-aspartate 4-semialdehyde + NADH
L-homoserine + NAD+
show the reaction diagram
O63067, O65027, Q3S3F6
-
-
-
r
L-aspartate 4-semialdehyde + NADPH
L-homoserine + NADP+
show the reaction diagram
-
-
-
-
r
L-aspartate 4-semialdehyde + NADPH
L-homoserine + NADP+
show the reaction diagram
-
-
-
-
?
L-aspartate 4-semialdehyde + NADPH
L-homoserine + NADP+
show the reaction diagram
O63067, O65027, Q3S3F6
-
-
-
r
L-aspartate 4-semialdehyde + NADPH
L-homoserine + NADP+
show the reaction diagram
-
part of the aspartate pathway of amino acid biosynthesis
-
-
r
L-aspartate 4-semialdehyde + NADPH + H+
L-homoserine + NADP+
show the reaction diagram
Lactobacillus plantarum, Lactobacillus plantarum NCIMB 8826
-
-
-
-
?
L-homoserine + NAD(P)+
L-aspartate 4-semialdehyde + NAD(P)H
show the reaction diagram
-
-
-
-
r
L-homoserine + NAD(P)+
L-aspartate 4-semialdehyde + NAD(P)H
show the reaction diagram
-
-
-
r
L-homoserine + NAD(P)+
L-aspartate 4-semialdehyde + NAD(P)H
show the reaction diagram
-
-
-
-
r
L-homoserine + NAD(P)+
L-aspartate 4-semialdehyde + NAD(P)H
show the reaction diagram
-
-
-
r
L-homoserine + NAD(P)+
L-aspartate 4-semialdehyde + NAD(P)H
show the reaction diagram
-
-
-
r
L-homoserine + NAD(P)+
L-aspartate 4-semialdehyde + NAD(P)H
show the reaction diagram
-
-
-
-
r
L-homoserine + NAD(P)+
L-aspartate 4-semialdehyde + NAD(P)H
show the reaction diagram
-
-
-
-
r
L-homoserine + NAD(P)+
L-aspartate 4-semialdehyde + NAD(P)H
show the reaction diagram
-
-
-
-
r
L-homoserine + NAD(P)+
L-aspartate 4-semialdehyde + NAD(P)H
show the reaction diagram
-
-
-
-
r
L-homoserine + NAD(P)+
L-aspartate 4-semialdehyde + NAD(P)H
show the reaction diagram
-
-
-
r
L-homoserine + NAD(P)+
L-aspartate 4-semialdehyde + NAD(P)H
show the reaction diagram
-
-
-
-
L-homoserine + NAD(P)+
L-aspartate 4-semialdehyde + NAD(P)H
show the reaction diagram
-
-
-
-
r
L-homoserine + NAD(P)+
L-aspartate 4-semialdehyde + NAD(P)H
show the reaction diagram
Thermophilic bacterium
-
-
-
r
L-homoserine + NAD(P)+
L-aspartate 4-semialdehyde + NAD(P)H
show the reaction diagram
Streptomyces clavuligerus, Streptomyces clavuligerus NRRL 3585
Q56R01
-
-
-
r
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH
show the reaction diagram
O63067, O65027, Q3S3F6
-
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH
show the reaction diagram
-
-
-
-
?
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH
show the reaction diagram
-
-
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH
show the reaction diagram
O81852
-
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH
show the reaction diagram
O63067, O65027, Q3S3F6
-
-
-
r
additional information
?
-
O63067, O65027, Q3S3F6
enzyme does not show aspartate kinase activity
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
show the reaction diagram
-
-
-
-
r
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
show the reaction diagram
-
kinetic mechanism
-
-
r
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
show the reaction diagram
-
kinetic mechanism
-
-
r
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
show the reaction diagram
-
third reaction in the pathway between aspartate and the amino acids threonine, isoleucine, methionine
-
-
r
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
show the reaction diagram
-
essential step in amino acids L-methionine, L-threonine, and L-isoleucine biosynthesis
-
-
?
L-aspartate 4-semialdehyde + NADPH
L-homoserine + NADP+
show the reaction diagram
-
part of the aspartate pathway of amino acid biosynthesis
-
-
r
L-homoserine + NAD(P)+
L-aspartate 4-semialdehyde + NAD(P)H
show the reaction diagram
Streptomyces clavuligerus, Streptomyces clavuligerus NRRL 3585
Q56R01
-
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH
show the reaction diagram
-
-
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
NAD+
Thermophilic bacterium
-
low activity
NADH
-
threonine sensitive isozyme can use NADPH or NADH, threonine insensitive isozyme can use NADPH only
NADH
O63067, O65027, Q3S3F6
GmHSD displays a 1.6fold preference for NADPH over NADH as the cofactor in the oxidation reaction. In the reduction reaction NADP+ is favored nearly 4fold as the cofactor
NADP+
-
-
NADP+
Thermophilic bacterium
-
preferred
NADPH
-
-
NADPH
-
threonine sensitive isozyme can use NADPH or NADH, threonine insensitive isozyme can use NADPH only
NADPH
-
-
NADPH
O63067, O65027, Q3S3F6
GmHSD displays a 1.6fold preference for NADPH over NADH as the cofactor in the oxidation reaction. In the reduction reaction NADP+ is favored nearly 4fold as the cofactor
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Cs+
-
activation of threonine sensitive enzyme
K+
-
activation of threonine sensitive isozyme
K+
Thermophilic bacterium
-
required
K+
-
activation
Li+
-
activation of threonine sensitive isozyme
Li+
Thermophilic bacterium
-
can partially replace K+
Mg2+
-
required for aspartate kinase activity
Na+
-
activation of threonine sensitive form
Na+
Thermophilic bacterium
-
can partially replace K+
Na+
-
activation
NH4+
-
activation of threonine sensitive isozyme
NH4+
Thermophilic bacterium
-
can partially replace K+
Rb+
Thermophilic bacterium
-
can partially replace K+
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(S)-2-amino-4-oxo-5-hydroxypentanoic acid
-
RI-331
2,2'-[thiobis[[2-(1,1-dimethylethyl)-5-methyl-4,1-phenylene]oxy]]bis-acetic acid diethyl ester
-
-
4,4'-thiobis[2-(1,1-dimethylethyl)]-5-methyl-phenol
-
-
4,4'-thiobis[2-(1,1-dimethylethyl)]-phenol
-
-
4,4'-thiobis[2-(1-methylethyl)]-phenol
-
-
4,4'-thiobis[5-methyl-2-(1-methylethyl)]-phenol
-
-
4,4'-[1,2-ethanediylbis(thio)]bis[2,6-bis(1-methylpropyl)]-phenol
-
-
4,4'-[1,2-ethanediylbis(thio)]bis[2-(1,1-dimethylethyl)-6-methyl]-phenol
-
-
4-(1-methylheptyl)-1,3-benzenediol
-
-
4-[[2-(2-furanyl)ethyl]thio]-phenol
-
-
4-[[[4-(1,1-dimethylethyl)phenyl]thio]methyl]-2,6-bis(1-methylethyl)-phenol
-
-
aspartate
-
-
bis(4-chlorophenyl)ethyloxiranyl-silane
-
-
D-threonine
Thermophilic bacterium
-
slight
DL-allo-threonine
Thermophilic bacterium
-
-
H-(1,2,4-triazol-3-yl)-DL-alanine
-
-
homoserine
-
-
L-cysteine
-
slight inhibition of chloroplast isozyme, strong inhibition of cytoplasmic isozyme
L-cysteine
-
-
L-cysteine
Thermophilic bacterium
-
slight
L-cysteine
-
-
L-cysteine
-
-
L-serine
-
-
L-threonine
-
-
L-threonine
-
degree of inhibition depends on age of plant; sensitive and insensitive isozymes
L-threonine
-
sensitive and insensitive isozymes
L-threonine
Thermophilic bacterium
-
-
L-threonine
-
not inhibitory
L-threonine
-
-
L-threonine
-
-
L-threonine
-
weakly inhibits reverse but not forward reaction
L-threonine
-
-
L-threonine
O81852
strong inhibition of both enzyme activities, aspartate dehydrogenase and aspartate kinase activity, by decreasing the affinity of the enzyme for substrate and cofactors, kinetic effects
L-threonine
-
the regulatory domain of the enzyme contains 2 binding sites, interaction with Gln443 leads to inhibition of the aspartate kinase activity and facilitates the binding of a second threonine on Gln524 leading to inhibition of the homoserine dehydrogenase activity, inhibition of the forward reactions
L-threonine
-
-
L-threonine
O63067, O65027, Q3S3F6
-
methionine
-
-
methionine
-
-
p-chloromercuribenzoate
-
-
Thr
-
90% inhibition of homoserine dehydrogenase 2 at 10 mM
threonine
-
the methionine-producing strain contains a deregulated homoserine dehydrogenase that is not sensitive to feedback inhibition as the wild-type enzyme
threonine
-
feedback inhibition, one isozyme is resistant and another is sensitive to threonine inhibition, 46.9% inhibition at 1 mM, 63.9% at 5 mM
Trifluoperazine
-
-
[2-(1,1-dimethylethyl)-4-[[5-(1,1-dimethylethyl)-4-hydroxy-2-methylphenyl]thio]-5-methylphenoxy]-acetic acid ethyl ester
-
-
methionine
-
weakly inhibits reverse but not forward reaction
additional information
-
no inhibition by [2-(1,1-dimethylethyl)-4-[[5-(1,1-dimethylethyl)-4-hydroxy-2-methylphenyl]thio]-5-methylphenoxy]-acetic acid and 4-amino-butyric acid 2-tert-butyl-4-(3-tert-butyl-4-hydroxy-phenylsulfanyl)-phenyl ester
-
additional information
-
Thr does not inhibit homoserine dehydrogenase 1
-
additional information
-
Lys, Met, and S-2-aminoethyl-L-cysteine do not affect HSDH activity at 1-5 mM
-
additional information
O63067, O65027, Q3S3F6
enzyme is not inhibited by other aspartate-derived amino acids than threonine
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Calmodulin
-
in the presence of above 0.1 mM Ca2+
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.04
aspartate 4-semialdehyde
-
isozyme II
5.5
ATP
O81852
pH 8.0, 37C, purified recombinant soluble enzyme
0.1
DL-aspartate 4-semialdehyde
-
-
11.6
L-aspartate
O81852
pH 8.0, 37C, purified recombinant soluble enzyme
0.066
L-aspartate 4-semialdehyde
-
isozyme I
0.08
L-aspartate 4-semialdehyde
-
threonine insensitive isozyme
0.098
L-aspartate 4-semialdehyde
O63067, O65027, Q3S3F6
cosubstrate NADPH, pH 8.0, 25C
0.1
L-aspartate 4-semialdehyde
-
isozyme I
0.13 - 0.15
L-aspartate 4-semialdehyde
-
threonine resistant isozyme
0.13 - 0.15
L-aspartate 4-semialdehyde
-
threonine resistant isozyme
0.17
L-aspartate 4-semialdehyde
-
-
0.24 - 0.25
L-aspartate 4-semialdehyde
-
threonine sensitive isozyme
0.24 - 0.25
L-aspartate 4-semialdehyde
-
threonine sensitive isozyme
0.36 - 0.4
L-aspartate 4-semialdehyde
-
isozyme II
0.5
L-aspartate 4-semialdehyde
-
threonine sensitive isozyme
0.5
L-aspartate 4-semialdehyde
-
-
0.569
L-aspartate 4-semialdehyde
O63067, O65027, Q3S3F6
cosubstrate NADH, pH 8.0, 25C
0.845
L-aspartate 4-semialdehyde
O63067, O65027, Q3S3F6
cosubstrate NADH, pH 8.0, 25C
1.19
L-aspartate 4-semialdehyde
O63067, O65027, Q3S3F6
cosubstrate NADH, pH 8.0, 25C
1.25
L-aspartate 4-semialdehyde
O63067, O65027, Q3S3F6
cosubstrate NADPH, pH 8.0, 25C
2.19
L-aspartate 4-semialdehyde
O63067, O65027, Q3S3F6
cosubstrate NADPH, pH 8.0, 25C
0.013
L-homoserine
-
-
0.275
L-homoserine
O63067, O65027, Q3S3F6
cosubstrate NADP+, pH 8.0, 25C
0.41
L-homoserine
-
recombinant hybrid bifunctional holoenzyme AKIII-HDHI+ containing the interface region, homoserine dehydrogenase activity
0.68
L-homoserine
-
recombinant isolated catalytic HDH-domain containing the interface region, homoserine dehydrogenase activity
0.69
L-homoserine
O63067, O65027, Q3S3F6
cosubstrate NADP+, pH 8.0, 25C
1.08
L-homoserine
O63067, O65027, Q3S3F6
cosubstrate NADP+, pH 8.0, 25C
1.2
L-homoserine
-
recombinant wild-type bifunctional holoenzyme, homoserine dehydrogenase activity
5.2
L-homoserine
O81852
pH 8.0, 37C, purified recombinant soluble enzyme
9.57
L-homoserine
O63067, O65027, Q3S3F6
cosubstrate NAD+, pH 8.0, 25C
13.4
L-homoserine
O63067, O65027, Q3S3F6
cosubstrate NAD+, pH 8.0, 25C
17.2
L-homoserine
-
recombinant isolated catalytic HDH-domain not containing the interface region, homoserine dehydrogenase activity
2.7
NAD+
O63067, O65027, Q3S3F6
pH 8.0, 25C
24.1
NAD+
O63067, O65027, Q3S3F6
pH 8.0, 25C
24.9
NAD+
O63067, O65027, Q3S3F6
pH 8.0, 25C
0.158
NADH
O63067, O65027, Q3S3F6
pH 8.0, 25C
0.19
NADH
O63067, O65027, Q3S3F6
pH 8.0, 25C
0.213
NADH
O63067, O65027, Q3S3F6
pH 8.0, 25C
0.3
NADH
-
-
0.46
NADH
-
isozyme II
0.034
NADP+
O63067, O65027, Q3S3F6
pH 8.0, 25C
0.073
NADP+
-
-
0.166
NADP+
O81852
pH 8.0, 37C, purified recombinant soluble enzyme
0.17 - 0.18
NADP+
Thermophilic bacterium
-
-
0.17 - 0.18
NADP+
-
-
0.235
NADP+
O63067, O65027, Q3S3F6
pH 8.0, 25C
0.245
NADP+
O63067, O65027, Q3S3F6
pH 8.0, 25C
0.027
NADPH
-
isozyme II
0.028
NADPH
O63067, O65027, Q3S3F6
pH 8.0, 25C
0.031
NADPH
-
threonine sensitive isozyme
0.032 - 0.036
NADPH
-
threonine resistant isozyme
0.032 - 0.036
NADPH
-
threonine resistant isozyme
0.039
NADPH
O63067, O65027, Q3S3F6
pH 8.0, 25C; pH 8.0, 25C
0.04
NADPH
-
threonine sensitive isozyme
0.043
NADPH
-
threonine sensitive isozyme
0.046
NADPH
-
isozyme I
0.09
NADPH
-
-
17.4
L-homoserine
O63067, O65027, Q3S3F6
cosubstrate NAD+, pH 8.0, 25C
additional information
additional information
O81852
kinetics
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2.8
L-aspartate 4-semialdehyde
O63067, O65027, Q3S3F6
cosubstrate NADPH, pH 8.0, 25C
9.68
L-aspartate 4-semialdehyde
O63067, O65027, Q3S3F6
cosubstrate NADH, pH 8.0, 25C
11.58
L-aspartate 4-semialdehyde
O63067, O65027, Q3S3F6
cosubstrate NADPH, pH 8.0, 25C
12.98
L-aspartate 4-semialdehyde
O63067, O65027, Q3S3F6
cosubstrate NADPH, pH 8.0, 25C
19.3
L-aspartate 4-semialdehyde
O63067, O65027, Q3S3F6
cosubstrate NADH, pH 8.0, 25C
22.58
L-aspartate 4-semialdehyde
O63067, O65027, Q3S3F6
cosubstrate NADH, pH 8.0, 25C
0.042
L-homoserine
O63067, O65027, Q3S3F6
cosubstrate NADP+, pH 8.0, 25C
0.052
L-homoserine
O63067, O65027, Q3S3F6
cosubstrate NADP+, pH 8.0, 25C
0.07
L-homoserine
O63067, O65027, Q3S3F6
cosubstrate NADP+, pH 8.0, 25C
0.24
L-homoserine
-
recombinant wild-type bifunctional holoenzyme, homoserine dehydrogenase activity
0.51
L-homoserine
-
recombinant isolated catalytic HDH-domain not containing the interface region, homoserine dehydrogenase activity
1.43
L-homoserine
O63067, O65027, Q3S3F6
cosubstrate NAD+, pH 8.0, 25C
3.3
L-homoserine
-
recombinant isolated catalytic HDH-domain containing the interface region, homoserine dehydrogenase activity
7
L-homoserine
O63067, O65027, Q3S3F6
cosubstrate NAD+, pH 8.0, 25C
10.15
L-homoserine
O63067, O65027, Q3S3F6
cosubstrate NAD+, pH 8.0, 25C
24
L-homoserine
-
recombinant hybrid bifunctional holoenzyme AKIII-HDHI+ containing the interface region, homoserine dehydrogenase activity
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
5.29
L-aspartate 4-semialdehyde
O63067, O65027, Q3S3F6
cosubstrate NADPH, pH 8.0, 25C
573
10.39
L-aspartate 4-semialdehyde
O63067, O65027, Q3S3F6
cosubstrate NADPH, pH 8.0, 25C
573
16.22
L-aspartate 4-semialdehyde
O63067, O65027, Q3S3F6
cosubstrate NADH, pH 8.0, 25C
573
17.02
L-aspartate 4-semialdehyde
O63067, O65027, Q3S3F6
cosubstrate NADH, pH 8.0, 25C
573
26.73
L-aspartate 4-semialdehyde
O63067, O65027, Q3S3F6
cosubstrate NADH, pH 8.0, 25C
573
28.54
L-aspartate 4-semialdehyde
O63067, O65027, Q3S3F6
cosubstrate NADPH, pH 8.0, 25C
573
0.039
L-homoserine
O63067, O65027, Q3S3F6
cosubstrate NADP+, pH 8.0, 25C
345
0.082
L-homoserine
O63067, O65027, Q3S3F6
cosubstrate NAD+, pH 8.0, 25C
345
0.095
L-homoserine
O63067, O65027, Q3S3F6
cosubstrate NADP+, pH 8.0, 25C
345
0.256
L-homoserine
O63067, O65027, Q3S3F6
cosubstrate NADP+, pH 8.0, 25C
345
0.731
L-homoserine
O63067, O65027, Q3S3F6
cosubstrate NAD+, pH 8.0, 25C
345
0.757
L-homoserine
O63067, O65027, Q3S3F6
cosubstrate NAD+, pH 8.0, 25C
345
0.281
NAD+
O63067, O65027, Q3S3F6
pH 8.0, 25C
7
0.421
NAD+
O63067, O65027, Q3S3F6
pH 8.0, 25C
7
0.53
NAD+
O63067, O65027, Q3S3F6
pH 8.0, 25C
7
61.29
NADH
O63067, O65027, Q3S3F6
pH 8.0, 25C
8
90.61
NADH
O63067, O65027, Q3S3F6
pH 8.0, 25C
8
118.9
NADH
O63067, O65027, Q3S3F6
pH 8.0, 25C
8
0.18
NADP+
O63067, O65027, Q3S3F6
pH 8.0, 25C
10
0.268
NADP+
O63067, O65027, Q3S3F6
pH 8.0, 25C
10
2.07
NADP+
O63067, O65027, Q3S3F6
pH 8.0, 25C
10
101.4
NADPH
O63067, O65027, Q3S3F6
pH 8.0, 25C
5
296.2
NADPH
O63067, O65027, Q3S3F6
pH 8.0, 25C
5
331.2
NADPH
O63067, O65027, Q3S3F6
pH 8.0, 25C
5
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
160 - 240
L-threonine
O63067, O65027, Q3S3F6
pH 8.0, 25C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.0044 - 0.0046
-
enzyme activity at different seed developmental stages, overview
5.4
O81852
purified recombinant soluble enzyme, forward reaction of aspartate kinase
13
O63067, O65027, Q3S3F6
pH 8.0, 25C
18.87
O81852
purified recombinant soluble enzyme, reverse reaction of homoserine dehydrogenase
343
-
-
360
-
-
additional information
-
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7
Q56R01
assay at
8
O81852
assay at
9.8
Thermophilic bacterium
-
-
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
8 - 10
Thermophilic bacterium
-
-
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
22
Q56R01
assay at room temperature
37
O81852
assay at
70
Thermophilic bacterium
-
-
additional information
-
above 50C temperature dependent conformational change
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
20 - 70
Thermophilic bacterium
-
no activity at 80C
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
-
akthr2 is not or time-restricted expressed in stem, gynoecium, and during seed formation
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
PDB
SCOP
CATH
ORGANISM
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thiobacillus denitrificans (strain ATCC 25259)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
34000
-
gel filtration, isozyme II, cytoplasm
246382
69000
-
gel filtration, isozyme II, cytoplasm
246382
70000
-
gel filtration, threonine insensitive isozyme
246385
70000
O63067, O65027, Q3S3F6
gel filtration
712490
75000
-
gel filtration, threonine insensitive isozyme
246388
80000
-
disc gel electrophoresis, threonine insensitive isozyme
246388
81000
-
gel filtration
246399
110000
-
gel filtration, sedimentation equilibrium centrifugation
246389
168000 - 174000
-
gel filtration, isozyme I, chloroplasts
246382
190000
-
gel filtration threonine sensitive isozyme
246385
220000
-
gel filtration, aggregated form
246389
220000
-
gel filtration
246395
280000
-
disc gel electrophoresis, threonine sensitive isozyme
246388
290000
-
gel filtration, threonine sensitive isozyme
246388
320000
O81852
in presence of L-threonine, gel filtration
642340
320000
-
wild-type enzyme in presence of L-threonine, gel filtration
642341
470000
O81852
in absence of L-threonine, gel filtration
642340
470000
-
wild-type enzyme in absence of L-threonine, mutant enzymes Q443A and Q524A both in presence or absence of L-threonine, gel filtration
642341
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 85000, SDS-PAGE, threonine sensitive isozyme
dimer
-
2 * 55000, SDS-PAGE
dimer
-
2 * 40000, SDS-PAGE
dimer
-
crystal structure
dimer
-
2 * 38000, SDS-PAGE, threonine resistant isozyme, x * 89000 + x * 93000, SDS-PAGE, threonine sensitive isozyme
dimer
O63067, O65027, Q3S3F6
2 * 40600, calculated, 2 * 40000, SDS-PAGE
tetramer
-
4 * 55000, SDS-PAGE
tetramer
-
x * 89000 + x * 93000, SDS-PAGE, threonine sensitive isozyme
tetramer
O81852
in presence of L-threonine
hexamer
O81852
in absence of L-threonine
additional information
-
primary and secondary structure comparison, the bifunctional enzyme contains 2 homologous subdomains defined by a common loop-alpha helix-loop-beta strand-loop-beta strand motif, the enzymes' regulatory domain is composed of 2 subdomains, amino acid residues 414-453 and 495-534
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
10 mg/ml purified recombinant enzyme, in TAPS, pH 8.5, in complex with inhibitor 4,4'-thiobis[2-(1-methylethyl)-phenol] in a molar ratio of 1:1, precipitant solution contains either 0.1 CHES, pH 9.5, 35% PEG 600 or 0.1 M CHES, pH 8.5, 40% PEG 400, and 0.2 M NaCl, 0.005 ml protein complex solution are equilibrated against 0.7 ml of precipitant solution using sitting drop technique, 3 months, X-ray diffraction structure determination and analysis at 3.0 A resolution, modeling
-
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
70
-
up to
246393
80
-
slow inactivation, protection by K+, Na+
246393
90
-
rapid inactivation
246393
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-80C, purified recombinant soluble enzyme, at 3 mg/ml, stable
O81852
-25C, 50 mM potassium phosphate buffer, pH 7.2, 15% v/v glycerol, 1 mM EDTA, 1 mM threonine, 14 mM 2-mercaptoethanol
-
-20C, 0.05 M potassium phosphate buffer, pH 7.5, 1.0 mM EDTA, 2.0 mM dithioerythritol, 5.0 mM L-threonine, 20% v/v glycerol, at least 2 years
-
-20C, 30 mM potassium phosphate buffer, pH 7.5, 50% v/v glycerol, threonine resistant isozyme at least 2 months stable, threonine sensitive isozyme at least 4 months stable
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant enzyme
-
native enzyme partially from seeds by ammonium sulfate fractionation and desalting gel filtration
-
recombinant separated catalytic domains
-
recombinant enzyme; recombinant enzyme; recombinant enzyme
O63067, O65027, Q3S3F6
separation of the two isozymes using Matrex Gel Red A affinity chromatography
-
separation of the two isozymes using Blue-Sepharose chromatography
-
overexpressed in Escherichia coli
-
-
Thermophilic bacterium
-
threonine sensitive and threonine insensitive isozymes
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
gene akthr2, DNA sequence determination and analysis, located on chromosome 4, subcloning in Escherichia coli strain DH5alpha, functional complementation of the Saccharomyces cerevisiae homoserine dehydrogenase-deficient hom6 mutant strain and of the aspartate kinase-deficient hom3 mutant strain, conferring L-threonine and L-methionine prototrophy to the yeast cells
-
overexpression of AK-HSDH isoform 1 in Escherichia coli
-
introduction of the gene homFBR allele into strain HL1049
-
both catalytic domains of the enzyme, performing each one of the enzyme activities, are expressed separately with or without the interface region, resulting in increased activity of each domain compared to the wild-type bifunctional holoenzyme, the isolated catalytic domains are no longer allosterically regulated, expression of hybrid holoenzyme AKIII-HDHI+
-
expression in Escherichia coli; expression in Escherichia coli; expression in Escherichia coli
O63067, O65027, Q3S3F6
expression in Escherichia coli
-
overexpression in Escherichia coli
-
gene hom, DNA and amino acid sequence determination and analysis, expression in the auxotroph mutant Escherichia coli CGSC 5075
Q56R01
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
strongly repressed by L-methionine
D8WXQ1, D8WXQ2
strongly repressed by L-threonine
D8WXQ1, D8WXQ2
strongly repressed by L-threonine
-
-
strongly repressed by L-methionine
-
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Q443A
-
site-directed mutagenesis, altered reaction kinetics for both activities and altered inhibition pattern by L-threonine compared to the wild-type enzyme, asparate kinase activity is completely insensitive to inhibition by L-threonine, overview
additional information
-
construction of transgenic Arabidopsis thaliana plants by transformation with gene akthr2 via Agrobacterium tumefaciens infection, determination of expression patterns of the gene akthr1 ans akthr2 in the transgenic plants
Q524A
-
site-directed mutagenesis, altered reaction kinetics for both activities and altered inhibition pattern by L-threonine compared to the wild-type enzyme, overview
additional information
-
heterologous expression in a hom-negative Escherichia coli mutant Gif 102, not able to grow on minimal medium unless added 1.5 mM of both L-threonine and L-methionine results in strains growing well on minimal agar plates without added threonine and methionine
additional information
-
heterologous expression in a hom-negative Escherichia coli mutant Gif 102, not able to grow on minimal medium unless added 1.5 mM of both L-threonine and L-methionine results in strains growing well on minimal agar plates without added threonine and methionine
-
G378E
-
feedback resistance of the enzyme
additional information
-
engineering of a Corynebacterium glutamicum strain HL1049 for effective production of methionine by elimination of the threonine synthesis gene and desensitizing the homoserine dehydrogenase versus inhibition by threonine, analysis of the amino acid spectrum of the engineered strain, overview
additional information
-
construction of a hybrid enzyme AKIII-HDHI+ by fusing a wild-type monofunctional aspartate kinase AKIII enzyme to the thrA2+ gene, encoding the homoserine dehydrogenase including the interface region of the wild-type bifunctional enzyme, the hybrid enzyme shows highly improved kinetic properties for homoserine dehydrogenase activity, and is not sensitive to L-threonine inhibition
H309A
-
decrease of catalytic activity and elimination of substrate inhibition
additional information
-
mutant strain M20-20D is deficient in gene HOM6 and shows no activity, the defect can be complemented by recombinant expression of the Arabidopsis thaliana gene akthr2 in the mutant yeast cells
additional information
Q56R01
construction of a hom disruption mutant by insertional inactivation via double crossover leading to up to 4.3fold and 2fold increases in intracellular free L-lysine concentration and specific cephamycin C production, respectively, during stationary phase in chemically defined medium, overview
additional information
Streptomyces clavuligerus NRRL 3585
-
construction of a hom disruption mutant by insertional inactivation via double crossover leading to up to 4.3fold and 2fold increases in intracellular free L-lysine concentration and specific cephamycin C production, respectively, during stationary phase in chemically defined medium, overview
-
Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
denatures in 3 M guanidine-HCl and refolds by simple dilution
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
synthesis
D8WXQ1, D8WXQ2
contrary to wild-type MGA3 cells that secrete 0.4 g/l L-lysine and 59 g/l L-glutamate under optimised fed batch methanol fermentation, the hom-1 mutant M168-20 secretes 11 g/l L-lysine and 69 g/l of L-glutamate. Overproduction of pyruvate carboxylase and its mutant enzyme P455S in M168-20 has no positive effect on the volumetric L-lysine yield and the L-lysine yield on methanol, and causes significantly reduced volumetric L-glutamate yield and L-glutamate yield on methanol
synthesis
-
contrary to wild-type MGA3 cells that secrete 0.4 g/l L-lysine and 59 g/l L-glutamate under optimised fed batch methanol fermentation, the hom-1 mutant M168-20 secretes 11 g/l L-lysine and 69 g/l of L-glutamate. Overproduction of pyruvate carboxylase and its mutant enzyme P455S in M168-20 has no positive effect on the volumetric L-lysine yield and the L-lysine yield on methanol, and causes significantly reduced volumetric L-glutamate yield and L-glutamate yield on methanol
-
pharmacology
-
enzyme is a target for inhibitor design for construction of antimicrobial agents