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 hide
1.1.1.3
-
RECOMMENDED NAME
GeneOntology No.
homoserine dehydrogenase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
L-homoserine + NAD(P)+ = L-aspartate 4-semialdehyde + NAD(P)H + H+
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
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).
CAS REGISTRY NUMBER
COMMENTARY hide
9028-13-1
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
two isozymes
-
-
Manually annotated by BRENDA team
barley
-
-
Manually annotated by BRENDA team
castor bean
-
-
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
strain NRRL 3585, gene hom
UniProt
Manually annotated by BRENDA team
Thermophilic bacterium
-
-
-
Manually annotated by BRENDA team
wheat
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
show the reaction diagram
L-aspartate 4-semialdehyde + NADH
L-homoserine + NAD+
show the reaction diagram
-
-
-
r
L-aspartate 4-semialdehyde + NADPH
L-homoserine + NADP+
show the reaction diagram
L-aspartate 4-semialdehyde + NADPH + H+
L-homoserine + NADP+
show the reaction diagram
L-homoserine + NAD(P)+
L-aspartate 4-semialdehyde + NAD(P)H
show the reaction diagram
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH
show the reaction diagram
-
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
show the reaction diagram
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
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH
show the reaction diagram
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NAD+
Thermophilic bacterium
-
low activity
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Mg2+
-
required for aspartate kinase activity
Rb+
Thermophilic bacterium
-
can partially replace K+
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
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
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-
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
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-
H-(1,2,4-triazol-3-yl)-DL-alanine
-
-
homoserine
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-
L-cysteine
L-serine
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-
L-threonine
methionine
p-chloromercuribenzoate
-
-
threonine
Trifluoperazine
-
-
[2-(1,1-dimethylethyl)-4-[[5-(1,1-dimethylethyl)-4-hydroxy-2-methylphenyl]thio]-5-methylphenoxy]-acetic acid ethyl ester
-
-
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Calmodulin
-
in the presence of above 0.1 mM Ca2+
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.04
aspartate 4-semialdehyde
-
isozyme II
5.5
ATP
pH 8.0, 37C, purified recombinant soluble enzyme
0.1
DL-aspartate 4-semialdehyde
-
-
11.6
L-aspartate
pH 8.0, 37C, purified recombinant soluble enzyme
0.066 - 2.19
L-aspartate 4-semialdehyde
0.013 - 17.4
L-homoserine
2.7 - 24.9
NAD+
0.158 - 0.46
NADH
0.034 - 0.245
NADP+
0.027 - 0.09
NADPH
additional information
additional information
kinetics
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2.8 - 22.58
L-aspartate 4-semialdehyde
0.042 - 24
L-homoserine
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
5.29 - 28.54
L-aspartate 4-semialdehyde
0.039 - 0.757
L-homoserine
0.281 - 0.53
NAD+
61.29 - 118.9
NADH
0.18 - 2.07
NADP+
101.4 - 331.2
NADPH
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
160 - 240
L-threonine
pH 8.0, 25C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.0044 - 0.0046
-
enzyme activity at different seed developmental stages, overview
5.4
purified recombinant soluble enzyme, forward reaction of aspartate kinase
18.87
purified recombinant soluble enzyme, reverse reaction of homoserine dehydrogenase
343
-
-
360
-
-
additional information
-
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
9.8
Thermophilic bacterium
-
-
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
8 - 10
Thermophilic bacterium
-
-
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
22
assay at room temperature
70
Thermophilic bacterium
-
-
additional information
-
above 50C temperature dependent conformational change
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
20 - 70
Thermophilic bacterium
-
no activity at 80C
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
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 hide
GeneOntology No.
LITERATURE
SOURCE
PDB
SCOP
CATH
ORGANISM
UNIPROT
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Sulfolobus tokodaii (strain DSM 16993 / JCM 10545 / NBRC 100140 / 7)
Sulfolobus tokodaii (strain DSM 16993 / JCM 10545 / NBRC 100140 / 7)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thiobacillus denitrificans (strain ATCC 25259)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
34000
-
gel filtration, isozyme II, cytoplasm
69000
-
gel filtration, isozyme II, cytoplasm
80000
-
disc gel electrophoresis, threonine insensitive isozyme
81000
-
gel filtration
110000
-
gel filtration, sedimentation equilibrium centrifugation
168000 - 174000
190000
-
gel filtration threonine sensitive isozyme
220000
280000
-
disc gel electrophoresis, threonine sensitive isozyme
290000
-
gel filtration, threonine sensitive isozyme
320000
470000
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
-
x * 85000, SDS-PAGE, threonine sensitive isozyme
hexamer
in absence of L-threonine
tetramer
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 hide
LITERATURE
80
-
slow inactivation, protection by K+, Na+
90
-
rapid inactivation
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-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
-
-25C, 50 mM potassium phosphate buffer, pH 7.2, 15% v/v glycerol, 1 mM EDTA, 1 mM threonine, 14 mM 2-mercaptoethanol
-
-80C, purified recombinant soluble enzyme, at 3 mg/ml, stable
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
native enzyme partially from seeds by ammonium sulfate fractionation and desalting gel filtration
-
overexpressed in Escherichia coli
-
recombinant enzyme
-
recombinant enzyme; recombinant enzyme; recombinant enzyme
recombinant separated catalytic domains
-
separation of the two isozymes using Blue-Sepharose chromatography
-
separation of the two isozymes using Matrex Gel Red A affinity chromatography
-
threonine sensitive and threonine insensitive isozymes
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
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; expression in Escherichia coli
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
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gene hom, DNA and amino acid sequence determination and analysis, expression in the auxotroph mutant Escherichia coli CGSC 5075
introduction of the gene homFBR allele into strain HL1049
-
overexpression in Escherichia coli
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overexpression of AK-HSDH isoform 1 in Escherichia coli
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
strongly repressed by L-methionine; strongly repressed by L-threonine
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
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
Q524A
-
site-directed mutagenesis, altered reaction kinetics for both activities and altered inhibition pattern by L-threonine compared to the wild-type enzyme, overview
G378E
-
feedback resistance of the enzyme
H309A
-
decrease of catalytic activity and elimination of substrate inhibition
additional information
Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
denatures in 3 M guanidine-HCl and refolds by simple dilution
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pharmacology
-
enzyme is a target for inhibitor design for construction of antimicrobial agents
synthesis
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