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Information on EC 1.1.1.3 - homoserine dehydrogenase
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EC Tree
1.1.1.3 homoserine dehydrogenaseIUBMB Comments
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).
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Word Map
- 1.1.1.3
- l-threonine
-
threonine-sensitive
- corynebacterium
- glutamicum
- l-lysine
- dihydrodipicolinate
- semialdehyde
- brevibacterium
-
2.7.2.4
- l-isoleucine
-
aspartate-derived
-
rhodospirillum
-
i-homoserine
-
lysine-sensitive
- lactofermentum
-
feedback-insensitive
-
feedback-resistant
-
flavum
- drug development
- synthesis
- pharmacology
The enzyme appears in viruses and cellular organisms
Synonyms
homoserine dehydrogenase, hsdh, ak-hsdh, hom-1, aspartokinase-homoserine dehydrogenase i, aspartate kinase-homoserine dehydrogenase, hsedh, ak-hdh, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
AK-HSDH
aspartate kinase-homoserine dehydrogenase
hom
hom-1
Hom6
homoserine dehydrogenase 1
homoserine dehydrogenase 2
HSD
HSDH
HseDH
orf19.2951
SACOL1362
aspartate kinase-homoserine dehydrogenase
-
bifunctional enzyme EC 2.7.2.4/EC 1.1.1.3
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
L-homoserine + NAD(P)+ = L-aspartate 4-semialdehyde + NAD(P)H + H+
-
-
-
-
L-homoserine + NAD(P)+ = L-aspartate 4-semialdehyde + NAD(P)H + H+
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+
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+
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+
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+
ordered bi bi kinetic mechanism in which nicotinamide cofactor binds first and leaves last in the reaction sequence
L-homoserine + NAD(P)+ = L-aspartate 4-semialdehyde + NAD(P)H + H+
role of conserved water molecules and a lysine residue in hydride transfer between the substrate and the cofactor. Lys105, which is located at the interface of the catalytic and cofactor-binding sites, mediates the hydride transfer step of the reaction mechanism of the enzyme. Potential reaction mechanisms for homoserine dehydrogenase, overview
L-homoserine + NAD(P)+ = L-aspartate 4-semialdehyde + NAD(P)H + H+
role of conserved water molecules and a lysine residue in hydride transfer between the substrate and the cofactor. Lys105, which is located at the interface of the catalytic and cofactor-binding sites, mediates the hydride transfer step of the reaction mechanism of the enzyme. Potential reaction mechanisms for homoserine dehydrogenase, overview
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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PATHWAY SOURCE
PATHWAYS
BRENDA
KEGG
MetaCyc
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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).
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CAS REGISTRY NUMBER
COMMENTARY
9028-13-1
-
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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
L-aspartate 4-semialdehyde + NADH
L-homoserine + NAD+
-
-
r
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH
-
-
r
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
-
kinetic mechanism
-
r
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
-
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)+
-
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)+
-
-
-
r
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
-
-
-
?
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
-
-
-
r
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
-
-
?
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
-
-
?
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
-
kinetic mechanism
-
r
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
-
essential step in amino acids L-methionine, L-threonine, and L-isoleucine biosynthesis
-
?
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
-
-
-
r
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
Thermophilic bacterium
-
-
-
r
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
-
-
-
r
L-aspartate 4-semialdehyde + NADPH
L-homoserine + NADP+
-
part of the aspartate pathway of amino acid biosynthesis
-
r
L-aspartate 4-semialdehyde + NADPH
L-homoserine + NADP+
-
-
r
L-aspartate 4-semialdehyde + NADPH + H+
L-homoserine + NADP+
-
-
-
?
L-aspartate 4-semialdehyde + NADPH + H+
L-homoserine + NADP+
Lactiplantibacillus plantarum NCIMB 8826
-
-
-
?
L-homoserine + NAD(P)+
L-aspartate 4-semialdehyde + NAD(P)H
-
-
-
?
L-homoserine + NAD(P)+
L-aspartate 4-semialdehyde + NAD(P)H
-
-
-
r
L-homoserine + NAD(P)+
L-aspartate 4-semialdehyde + NAD(P)H
-
-
-
r
L-homoserine + NAD(P)+
L-aspartate 4-semialdehyde + NAD(P)H
-
-
r
L-homoserine + NAD(P)+
L-aspartate 4-semialdehyde + NAD(P)H
-
-
-
r
L-homoserine + NAD(P)+
L-aspartate 4-semialdehyde + NAD(P)H
-
-
r
L-homoserine + NAD(P)+
L-aspartate 4-semialdehyde + NAD(P)H
-
-
r
L-homoserine + NAD(P)+
L-aspartate 4-semialdehyde + NAD(P)H
Thermophilic bacterium
-
-
-
r
L-homoserine + NAD(P)+
L-aspartate 4-semialdehyde + NAD(P)H + H+
-
-
r
L-homoserine + NAD(P)+
L-aspartate 4-semialdehyde + NAD(P)H + H+
Sulfurisphaera tokodaii DSM 16993 / JCM 10545 / NBRC 100140 / 7
-
-
r
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH + H+
-
-
r
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH + H+
-
-
r
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH + H+
-
-
r
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH + H+
Sulfurisphaera tokodaii DSM 16993 / JCM 10545 / NBRC 100140 / 7
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH
-
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
Candida albicans SC5314 / ATCC MYA-2876
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
no activity of the wild-type enzyme with NADP+, but only with enzyme mutants R40A and K57A
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
no activity of the wild-type enzyme with NADP+, but only with enzyme mutants R40A and K57A
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
r
additional information
?
-
enzyme does not show aspartate kinase activity
-
?
additional information
?
-
enzyme does not show aspartate kinase activity
-
?
additional information
?
-
enzyme does not show aspartate kinase activity
-
?
additional information
?
-
-
enzyme does not show aspartate kinase activity
-
?
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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
L-aspartate 4-semialdehyde + NADPH
L-homoserine + NADP+
-
part of the aspartate pathway of amino acid biosynthesis
-
-
r
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
-
kinetic mechanism
-
-
r
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
-
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)+
-
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)+
-
kinetic mechanism
-
-
r
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
-
essential step in amino acids L-methionine, L-threonine, and L-isoleucine biosynthesis
-
-
?
L-homoserine + NAD(P)+
L-aspartate 4-semialdehyde + NAD(P)H
-
-
-
r
L-homoserine + NAD(P)+
L-aspartate 4-semialdehyde + NAD(P)H
-
-
-
r
L-homoserine + NAD(P)+
L-aspartate 4-semialdehyde + NAD(P)H + H+
-
-
-
r
L-homoserine + NAD(P)+
L-aspartate 4-semialdehyde + NAD(P)H + H+
Sulfurisphaera tokodaii DSM 16993 / JCM 10545 / NBRC 100140 / 7
-
-
-
r
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH + H+
-
-
-
r
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH + H+
-
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
Candida albicans SC5314 / ATCC MYA-2876
-
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
r
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
NADP does not act as a cofactor for this enzyme, but as a strong inhibitor of NAD+-dependent oxidation of Hse, analysis of the cofactor-binding site of the enzyme, Pyrococcus horikoshii HseDH shows a unique cofactor binding mode, which is not observed in conventional NAD(P)-dependent dehydrogenases. Superposition of the Hse/NADPH-bound K57A structure onto the NADPH-bound wild-type structure shows that the NADPH molecule in the mutant structure is positioned/configured nearly identically to the NADPH molecule in the wild-type structure, except for the positioning of the C2 phosphate group of the adenine ribose. The C2 phosphate is tightly held in position through five surrounding hydrogen bonds in the wild-type enzyme. In K57A mutant the C2 phosphate group is rotates in a clockwise direction around C2B of NADPH by about 30° relative to the wild-type structure. The guanidino group of Arg40 in the mutant is also rotated clockwise by about 90° around the NE atom of Arg40 relative to the wild-type structure
-
NADH
-
threonine sensitive isozyme can use NADPH or NADH, threonine insensitive isozyme can use NADPH only
NADH
-
threonine sensitive isozyme can use NADPH or NADH, threonine insensitive isozyme can use NADPH only
NADH
-
threonine sensitive isozyme can use NADPH or NADH, threonine insensitive isozyme can use NADPH only
NADH
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+
no activity of the wild-type enzyme with NADP+, but only with enzyme mutants R40A and K57A
NADPH
-
threonine sensitive isozyme can use NADPH or NADH, threonine insensitive isozyme can use NADPH only
NADPH
-
threonine sensitive isozyme can use NADPH or NADH, threonine insensitive isozyme can use NADPH only
NADPH
-
threonine sensitive isozyme can use NADPH or NADH, threonine insensitive isozyme can use NADPH only
NADPH
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
NADPH
no activity of the wild-type enzyme with NADPH, but only with enzyme mutants R40A and K57A
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Cs+
K+
Li+
Mg2+
Na+
NH4+
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1-[(1S,2S)-2-(bromomethyl)cyclopropyl]-4-[(trifluoromethyl)sulfanyl]benzene
-
2,2'-[thiobis[[2-(1,1-dimethylethyl)-5-methyl-4,1-phenylene]oxy]]bis-acetic acid diethyl ester
-
-
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-(4-hydroxy-3-isopropylphenylthio)-2-isopropylphenol
competitive to L-aspartate 4-semialdehyde, enzyme binding structure anaysis from crystal structure, overview
4-[[[4-(1,1-dimethylethyl)phenyl]thio]methyl]-2,6-bis(1-methylethyl)-phenol
-
-
L-lysine
allosteric regulation of recombinant engineered homoserine dehydrogenase by nonnatural inhibitor L-lysine
[2-(1,1-dimethylethyl)-4-[[5-(1,1-dimethylethyl)-4-hydroxy-2-methylphenyl]thio]-5-methylphenoxy]-acetic acid ethyl ester
-
-
L-cysteine
-
slight inhibition of chloroplast isozyme, strong inhibition of cytoplasmic isozyme
L-cysteine
-
slight inhibition of chloroplast isozyme, strong inhibition of cytoplasmic isozyme
L-threonine
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
the enzyme activity is subjected to feedback regulation by L-threonine
L-threonine
the natural threonine binding sites of the enzyme are predicted and verified by mutagenesis experiments
L-threonine
-
degree of inhibition depends on age of plant; sensitive and insensitive isozymes
L-threonine
-
degree of inhibition depends on age of plant; sensitive and insensitive isozymes
L-threonine
-
degree of inhibition depends on age of plant; sensitive and insensitive isozymes
NADP+
NADP+ does not act as a cofactor for this enzyme, but as a strong inhibitor of NAD+-dependent oxidation of Hse, evaluation of the factors responsible for the NADP+-mediated inhibition
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
threonine
-
the methionine-producing strain contains a deregulated homoserine dehydrogenase that is not sensitive to feedback inhibition as the wild-type enzyme
additional information
-
Lys, Met, and S-2-aminoethyl-L-cysteine do not affect HSDH activity at 1-5 mM
-
additional information
the natural threonine binding sites of the enzyme are engineered to a lysine binding pocket. The reengineered enzyme only responds to lysine inhibition but not to threonine
-
additional information
-
the natural threonine binding sites of the enzyme are engineered to a lysine binding pocket. The reengineered enzyme only responds to lysine inhibition but not to threonine
-
additional information
enzyme is not inhibited by other aspartate-derived amino acids than threonine
-
additional information
enzyme is not inhibited by other aspartate-derived amino acids than threonine
-
additional information
enzyme is not inhibited by other aspartate-derived amino acids than threonine
-
additional information
-
enzyme is not inhibited by other aspartate-derived amino acids than threonine
-
additional information
-
Thr does not inhibit homoserine dehydrogenase 1
-
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
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
dithiothreitol
the enzyme is 2.5fold activated by the addition of 0.8 mM dithiothreitol. The activation is caused by cleavage of the disulfide bond formed between two cysteine residues in the C-terminal regions of the two subunits
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
11.6
L-aspartate
pH 8.0, 37°C, purified recombinant soluble enzyme
0.098
L-aspartate 4-semialdehyde
cosubstrate NADPH, pH 8.0, 25°C
0.15
L-aspartate 4-semialdehyde
-
threonine-resistant enzyme, pH and temperature not specified in the publication
0.25
L-aspartate 4-semialdehyde
-
threonine-sensitive enzyme, pH and temperature not specified in the publication
0.569
L-aspartate 4-semialdehyde
cosubstrate NADH, pH 8.0, 25°C
0.845
L-aspartate 4-semialdehyde
cosubstrate NADH, pH 8.0, 25°C
1.19
L-aspartate 4-semialdehyde
cosubstrate NADH, pH 8.0, 25°C
1.25
L-aspartate 4-semialdehyde
cosubstrate NADPH, pH 8.0, 25°C
2.19
L-aspartate 4-semialdehyde
cosubstrate NADPH, pH 8.0, 25°C
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
1.2
L-homoserine
-
recombinant wild-type bifunctional holoenzyme, homoserine dehydrogenase activity
5.2
L-homoserine
pH 8.0, 37°C, purified recombinant soluble enzyme
17.2
L-homoserine
-
recombinant isolated catalytic HDH-domain not containing the interface region, homoserine dehydrogenase activity
0.46
NADH
-
isoenzyme II, at pH 7.5, temperature not specified in the publication
0.036
NADPH
-
threonine-resistant enzyme, pH and temperature not specified in the publication
0.04
NADPH
-
threonine-sensitive enzyme, pH and temperature not specified in the publication
additional information
additional information
enzyme HseDH shows typical Michaelis-Menten kinetics for oxidation
-
additional information
additional information
kinetic profile
-
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2.8
L-aspartate 4-semialdehyde
cosubstrate NADPH, pH 8.0, 25°C
9.68
L-aspartate 4-semialdehyde
cosubstrate NADH, pH 8.0, 25°C
11.58
L-aspartate 4-semialdehyde
cosubstrate NADPH, pH 8.0, 25°C
12.98
L-aspartate 4-semialdehyde
cosubstrate NADPH, pH 8.0, 25°C
19.3
L-aspartate 4-semialdehyde
cosubstrate NADH, pH 8.0, 25°C
22.58
L-aspartate 4-semialdehyde
cosubstrate NADH, pH 8.0, 25°C
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
3.3
L-homoserine
-
recombinant isolated catalytic HDH-domain containing the interface region, homoserine dehydrogenase activity
24
L-homoserine
-
recombinant hybrid bifunctional holoenzyme AKIII-HDHI+ containing the interface region, homoserine dehydrogenase activity
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
5.29
L-aspartate 4-semialdehyde
cosubstrate NADPH, pH 8.0, 25°C
10.39
L-aspartate 4-semialdehyde
cosubstrate NADPH, pH 8.0, 25°C
16.22
L-aspartate 4-semialdehyde
cosubstrate NADH, pH 8.0, 25°C
17.02
L-aspartate 4-semialdehyde
cosubstrate NADH, pH 8.0, 25°C
26.73
L-aspartate 4-semialdehyde
cosubstrate NADH, pH 8.0, 25°C
28.54
L-aspartate 4-semialdehyde
cosubstrate NADPH, pH 8.0, 25°C
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0131
(2S)-2-[[4-(propan-2-yl)phenyl]sulfanyl]propanenitrile
pH and temperature not specified in the publication
0.01307
1-tert-butyl-4-[(difluoromethyl)sulfanyl]benzene
pH and temperature not specified in the publication
0.00963
1-[(1S,2S)-2-(bromomethyl)cyclopropyl]-4-[(trifluoromethyl)sulfanyl]benzene
pH and temperature not specified in the publication
0.01568
3-[(4-tert-butylphenyl)sulfanyl]propane-1-thiol
pH and temperature not specified in the publication
0.01
4-(4-hydroxy-3-isopropylphenylthio)-2-isopropylphenol
pH and temperature not specified in the publication
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.0044 - 0.0046
-
enzyme activity at different seed developmental stages, overview
18.87
purified recombinant soluble enzyme, reverse reaction of homoserine dehydrogenase
5.4
purified recombinant soluble enzyme, forward reaction of aspartate kinase
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
8.5
the catalytic activity of the enzyme for the conversion of L-homoserine to L-aspartate 4-semialdehyde (the reverse reaction) is enhanced at basic pH
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30
37
additional information
-
above 50°C temperature dependent conformational change
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TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
bifunctional enzyme showing aspartate dehydrogenase and aspartate kinase activity
-
-
brenda
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
brenda
var. Bensheim showing threonine and methionine prototrophy, bifunctional enzyme showing aspartate dehydrogenase and aspartate kinase activity, gene akthr2
-
-
brenda
a methionine-producing strain carrying mutations in the hom and the thrB genes
-
-
brenda
bifunctional aspartokinase-homoserine dehydrogenase AK-HSD-1
UniProt
brenda
bifunctional aspartokinase-homoserine dehydrogenase AK-HSD-2
UniProt
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
-
akthr2 is not or time-restricted expressed in stem, gynoecium, and during seed formation
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
metabolism
physiological function
additional information
evolution
the catalytic region of the enzyme is unique, the nucleotide-binding domain conforms to the Rossmann fold-like conventional NAD(P)-dependent dehydrogenases
evolution
-
the catalytic region of the enzyme is unique, the nucleotide-binding domain conforms to the Rossmann fold-like conventional NAD(P)-dependent dehydrogenases
malfunction
HOM6 deletions cause translational arrest in cells grown under amino acid starvation conditions. HOM6 deletion reduces Candida albicans cell adhesion to polystyrene, which is a common plastic used in many medical devices. HOM6-homozygous mutants are hypersensitive to hygromycin B and cycloheximide as compared with wild-type, HOM6-heterozygous, and HOM6-reintegrated strains. HOM6 deletion affects translation and leads to the accumulation of free ribosomes
malfunction
Candida albicans SC5314 / ATCC MYA-2876
-
HOM6 deletions cause translational arrest in cells grown under amino acid starvation conditions. HOM6 deletion reduces Candida albicans cell adhesion to polystyrene, which is a common plastic used in many medical devices. HOM6-homozygous mutants are hypersensitive to hygromycin B and cycloheximide as compared with wild-type, HOM6-heterozygous, and HOM6-reintegrated strains. HOM6 deletion affects translation and leads to the accumulation of free ribosomes
metabolism
homoserine dehydrogenase (HSD) is an oxidoreductase in the aspartic acid pathway. The L-homoserine produced by this enzyme at the first branch point of the aspartic acid pathway is a precursor for essential amino acids such as L-threonine, L-methionine and L-isoleucine
metabolism
homoserine dehydrogenase (HSD) is an oxidoreductase that is involved in the reversible conversion of L-aspartate semialdehyde to L-homoserine in a dinucleotide cofactor-dependent reduction reaction. HSD is thus a crucial intermediate enzyme linked to the biosynthesis of several essential amino acids such as lysine, methionine, isoleucine and threonine
metabolism
homoserine dehydrogenase activity and is involved in the biosynthesis of methionine and threonine
metabolism
homoserine dehydrogenase is a key enzyme in the L-threonine pathway
metabolism
-
homoserine dehydrogenase (HSD) is an oxidoreductase in the aspartic acid pathway. The L-homoserine produced by this enzyme at the first branch point of the aspartic acid pathway is a precursor for essential amino acids such as L-threonine, L-methionine and L-isoleucine
metabolism
-
homoserine dehydrogenase (HSD) is an oxidoreductase that is involved in the reversible conversion of L-aspartate semialdehyde to L-homoserine in a dinucleotide cofactor-dependent reduction reaction. HSD is thus a crucial intermediate enzyme linked to the biosynthesis of several essential amino acids such as lysine, methionine, isoleucine and threonine
metabolism
-
homoserine dehydrogenase is a key enzyme in the L-threonine pathway
metabolism
Candida albicans SC5314 / ATCC MYA-2876
-
homoserine dehydrogenase activity and is involved in the biosynthesis of methionine and threonine
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
physiological function
homoserine dehydrogenase catalyzes an NAD(P)-dependent reversible reaction between L-homoserine and aspartate 4-semialdehyde and is involved in the aspartate pathway
physiological function
the enzyme coordinates a critical branch point of the metabolic pathway that leads to the synthesis of bacterial cell-wall components such as L-lysine and m-DAP in addition to other amino acids such as L-threonine, L-methionine and L-isoleucine. The kinetic behaviour of Staphylococcus aureus HSD is not altered in the presence of plausible allosteric inhibitors such as L-threonine and L-serine
physiological function
the enzyme is involved in cell-wall maintenance and essential amino acid biosynthesis. Homoserine dehydrogenase catalyzes a reaction at the branch point of the pathway leading to lysine biosynthesis. This pathway is also referred to as the diaminopimelate (dap) pathway
physiological function
the enzyme is naturally allosterically regulated by threonine and isoleucine
physiological function
-
the enzyme coordinates a critical branch point of the metabolic pathway that leads to the synthesis of bacterial cell-wall components such as L-lysine and m-DAP in addition to other amino acids such as L-threonine, L-methionine and L-isoleucine. The kinetic behaviour of Staphylococcus aureus HSD is not altered in the presence of plausible allosteric inhibitors such as L-threonine and L-serine
physiological function
-
the enzyme is involved in cell-wall maintenance and essential amino acid biosynthesis. Homoserine dehydrogenase catalyzes a reaction at the branch point of the pathway leading to lysine biosynthesis. This pathway is also referred to as the diaminopimelate (dap) pathway
physiological function
Sulfurisphaera tokodaii DSM 16993 / JCM 10545 / NBRC 100140 / 7
-
homoserine dehydrogenase catalyzes an NAD(P)-dependent reversible reaction between L-homoserine and aspartate 4-semialdehyde and is involved in the aspartate pathway
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
additional information
structural basis for the catalytic mechanism of homoserine dehydrogenase, the cofactor-binding site and catalytic site are docked with the cofactor NADP+ and L-homoserine, respectively, modelling, overview
additional information
-
structural basis for the catalytic mechanism of homoserine dehydrogenase, the cofactor-binding site and catalytic site are docked with the cofactor NADP+ and L-homoserine, respectively, modelling, overview
additional information
structure homology modelling using the template, homoserine dehydrogenase from Thiobacillus denitrificans, PDB ID 3MTJ, three-dimensional structure analysis and molecular dynamics simulation, overview. Identification of substrate- and cofactor-binding regions. In L-aspartate semialdehyde binding, the substrate docks to the protein involving residues Thr163, Asp198, and Glu192, which may be important because they form a hydrogen bond with the enzyme. Key recognition residues are Lys107 and Lys207
additional information
-
structure homology modelling using the template, homoserine dehydrogenase from Thiobacillus denitrificans, PDB ID 3MTJ, three-dimensional structure analysis and molecular dynamics simulation, overview. Identification of substrate- and cofactor-binding regions. In L-aspartate semialdehyde binding, the substrate docks to the protein involving residues Thr163, Asp198, and Glu192, which may be important because they form a hydrogen bond with the enzyme. Key recognition residues are Lys107 and Lys207
additional information
-
structural basis for the catalytic mechanism of homoserine dehydrogenase, the cofactor-binding site and catalytic site are docked with the cofactor NADP+ and L-homoserine, respectively, modelling, overview
Show AA Sequence and Transmembrane Helices (44081 entries)
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PDB
SCOP
CATH
UNIPROT
ORGANISM
Mycolicibacterium hassiacum (strain DSM 44199 / CIP 105218 / JCM 12690 / 3849)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Sulfurisphaera tokodaii (strain DSM 16993 / JCM 10545 / NBRC 100140 / 7)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thiobacillus denitrificans (strain ATCC 25259)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Sulfurisphaera tokodaii (strain DSM 16993 / JCM 10545 / NBRC 100140 / 7)
Sulfurisphaera tokodaii (strain DSM 16993 / JCM 10545 / NBRC 100140 / 7)
Sulfurisphaera tokodaii (strain DSM 16993 / JCM 10545 / NBRC 100140 / 7)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
168000 - 174000
220000
320000
40000
470000
55000
70000
75000
470000
-
wild-type enzyme in absence of L-threonine, mutant enzymes Q443A and Q524A both in presence or absence of L-threonine, gel filtration
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
homodimer
tetramer
additional information
homodimer
-
2 * 36925, sequence calculation, 2 * 40000, SDS-PAGE
homodimer
the enzyme is a dimer in solution as well as in the crystal. Enzyme HSD from stapylococcus aureus is an elongated molecule with three domains: a nucleotide cofactor binding domain at the N-terminus, a central catalytic domain and a C-terminal ACT domain, structure overview
homodimer
-
the enzyme is a dimer in solution as well as in the crystal. Enzyme HSD from stapylococcus aureus is an elongated molecule with three domains: a nucleotide cofactor binding domain at the N-terminus, a central catalytic domain and a C-terminal ACT domain, structure overview
homodimer
Sulfurisphaera tokodaii DSM 16993 / JCM 10545 / NBRC 100140 / 7
-
dimeric enzyme structure, overview
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
additional information
structure homology modelling, three-dimensional structure analysis and molecular dynamics simulation, overview
additional information
-
structure homology modelling, three-dimensional structure analysis and molecular dynamics simulation, overview
additional information
structural basis for the catalytic mechanism of homoserine dehydrogenase, overview
additional information
-
structural basis for the catalytic mechanism of homoserine dehydrogenase, overview
additional information
-
structural basis for the catalytic mechanism of homoserine dehydrogenase, overview
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
for the purified ligand-free recombinant wild-type enzyme: sitting drop vapor diffusion method, mixing of 0.001 ml of 12.0 mg/ml protein solution with an equal volume of mother liquor composed of 0.1 M potassium phosphate, pH 6.2, and 20% MPD, 2 days, 20°C, for the homoserine-bound K57A mutant enzyme: sitting drop vapor diffusion method, mixing of 0.002 ml of 10 mg/ml protein solution containing 1 mM homoserine with 0.002 ml of mother liquor containing 16% polyethylene glycol monomethyl ether 2000 and 0.1 M citrate buffer, pH 6.5, 7 days, 20°C, X-ray diffraction structure determination and analysis at 2.3 A resolution, molecular replacement and modelling
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
-
purified enzyme, crystallization at different pH values in the range of pH 6.0-8.5, hanging drop and sitting drop methods of vapour diffusion, 8 mg/ml protein solution is mixed with reservoir solution, different conditions involving addition of 0.2 M magnesium acetate and PEG 3350 or 8000, and 3.5% glycerol, overview. X-ray diffraction structure determination and analysis at 2.1-2.2 A resolution
purified enzyme, crystallization at different pH values in the range of pH 6.0-8.5, X-ray diffraction structure determination and analysis at 2.1-2.2 A resolution
purified recombinant enzyme in oxidized and in reduced form, hanging drop vapor diffusion method, for the oxidized form: mixing of 0.0015 ml of 5.9 mg/ml protein solution with 0.0015 ml of reservoir solution, pH 4.1, containing 9.5% w/v PEG 3350, 19% w/v PEG 400, 0.19 M magnesium chloride, and 2.5% DMSO, for the reduced form: soaking of the oxidized enzyme crystals in a solution consisting of 0.003 ml of reservoir solution and 0.001 ml of 200 mM DTT for 60 min prior to the first diffraction data collection, 12°C, X-ray diffraction structure determmination and analysis at 1.60-1.83 A resolution, molecular replacement and modelling
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PROTEIN VARIANTS
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
Q524A
-
site-directed mutagenesis, altered reaction kinetics for both activities and altered inhibition pattern by L-threonine compared to the wild-type enzyme, overview
G378S
L200F
-
site-directed mutagenesis, compared to mutant L200F, the double mutant shows 2 degree higher optimum temperature, 1.24 times higher activity, but the same pH optimum of pH 7.5 as mutant L200F. Both mutants L200F/D215K and L200F show good resistance to organic solvents and metal ions
L200F/D215K
-
site-directed mutagenesis, compared to mutant L200F, the double mutant shows 2 dgree higher optimum temperature, 1.24 times higher activity, but the same pH optimum of pH 7.5 as mutant L200F. Both mutants L200F/D215K and L200F show good resistance to organic solvents and metal ions
L200F
-
site-directed mutagenesis, compared to mutant L200F, the double mutant shows 2 degree higher optimum temperature, 1.24 times higher activity, but the same pH optimum of pH 7.5 as mutant L200F. Both mutants L200F/D215K and L200F show good resistance to organic solvents and metal ions
L200F/D215K
-
site-directed mutagenesis, compared to mutant L200F, the double mutant shows 2 dgree higher optimum temperature, 1.24 times higher activity, but the same pH optimum of pH 7.5 as mutant L200F. Both mutants L200F/D215K and L200F show good resistance to organic solvents and metal ions
K57Aa
site-directed mutagenesis, in contrast to the wild-type enzyme, the mutant enzyme shows catalytic activity with NADP+, the activity with NAD+ is increased compared to the wild-type enzyme
R40A
site-directed mutagenesis, in contrast to the wild-type enzyme, the mutant enzyme shows catalytic activity with NADP+, the activity with NAD+ is decreased compared to the wild-type enzyme
K57Aa
-
site-directed mutagenesis, in contrast to the wild-type enzyme, the mutant enzyme shows catalytic activity with NADP+, the activity with NAD+ is increased compared to the wild-type enzyme
R40A
-
site-directed mutagenesis, in contrast to the wild-type enzyme, the mutant enzyme shows catalytic activity with NADP+, the activity with NAD+ is decreased compared to the wild-type enzyme
H309A
decrease of catalytic activity and elimination of substrate inhibition
additional information
G378S
construction of a homoserine dehydrogenase mutant HDG378S, encoded by hom1, in Corynebacterium glutamicum strain IWJ001, one of the best L-isoleucine producing strains. Strain HDG378S is partially resistant to L-threonine with the half maximal inhibitory concentration between 12 and 14 mM. Overexpression of lysC1, hom1 and thrB1 increased L-threonine and L-lysine production in Corynebacterium glutamicum ATCC13869 by 96folds and 21.2folds, respectively, overview
G378S
-
construction of a homoserine dehydrogenase mutant HDG378S, encoded by hom1, in Corynebacterium glutamicum strain IWJ001, one of the best L-isoleucine producing strains. Strain HDG378S is partially resistant to L-threonine with the half maximal inhibitory concentration between 12 and 14 mM. Overexpression of lysC1, hom1 and thrB1 increased L-threonine and L-lysine production in Corynebacterium glutamicum ATCC13869 by 96folds and 21.2folds, respectively, 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
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
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
additional information
generation of HOM6-deleted (HOM6/hom6DELT and hom6DELTA/hom6DELTA) and HOM6-reintegrated (hom6DELTA/hom6DELTA::HOM6 and hom6DELTA::HOM6/hom6DELTA::HOM6) strains
additional information
-
generation of HOM6-deleted (HOM6/hom6DELT and hom6DELTA/hom6DELTA) and HOM6-reintegrated (hom6DELTA/hom6DELTA::HOM6 and hom6DELTA::HOM6/hom6DELTA::HOM6) strains
additional information
Candida albicans SC5314 / ATCC MYA-2876
-
generation of HOM6-deleted (HOM6/hom6DELT and hom6DELTA/hom6DELTA) and HOM6-reintegrated (hom6DELTA/hom6DELTA::HOM6 and hom6DELTA::HOM6/hom6DELTA::HOM6) strains
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
design of an artificial allosteric enzyme to sense an unnatural signal for a precise and dynamical control of fluxes of growth-essential but byproduct pathways in metabolic engineering of industrial microorganisms. The natural threonine binding sites of the enzyme are engineered to a lysine binding pocket. The reengineered enzyme only responds to lysine inhibition but not to threonine
additional information
-
design of an artificial allosteric enzyme to sense an unnatural signal for a precise and dynamical control of fluxes of growth-essential but byproduct pathways in metabolic engineering of industrial microorganisms. The natural threonine binding sites of the enzyme are engineered to a lysine binding pocket. The reengineered enzyme only responds to lysine inhibition but not to threonine
additional information
releasing the enzymes of the L-threonine biosynthesis pathway from feedback control and coordinating their expression plays a pivotal role in engineering Corynebacterium glutamicum into L-isoleucine producers, construction of transgenic Corynebacterium glutamicum with deregulated L-threonine biosynthesis pathway enzymes for enhanced L-isoleucine biosynthesis
additional information
-
releasing the enzymes of the L-threonine biosynthesis pathway from feedback control and coordinating their expression plays a pivotal role in engineering Corynebacterium glutamicum into L-isoleucine producers, construction of transgenic Corynebacterium glutamicum with deregulated L-threonine biosynthesis pathway enzymes for enhanced L-isoleucine biosynthesis
additional information
-
releasing the enzymes of the L-threonine biosynthesis pathway from feedback control and coordinating their expression plays a pivotal role in engineering Corynebacterium glutamicum into L-isoleucine producers, construction of transgenic Corynebacterium glutamicum with deregulated L-threonine biosynthesis pathway enzymes for enhanced L-isoleucine biosynthesis
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
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
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
-
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
-
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
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pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5 - 12
purified recombinant His-tagged enzyme, 10 min, 50°C, stable at
741408
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
-
half-life of mutant L200F/D215K is 4.16 h, of mutant L200F 3.71 h
75
purified recombinant His-tagged enzyme, 10 min, retains full activity
90
90
purified recombinant His-tagged enzyme, 10 min, retains 70% activity
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ORGANIC SOLVENT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
both mutants L200F/D215K and L200F show good resistance to organic solvents and metal ions
additional information
-
both mutants L200F/D215K and L200F show good resistance to organic solvents and metal ions
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, 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
-
-20°C, 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
-
-25°C, 50 mM potassium phosphate buffer, pH 7.2, 15% v/v glycerol, 1 mM EDTA, 1 mM threonine, 14 mM 2-mercaptoethanol
-
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
native enzyme partially from seeds by ammonium sulfate fractionation and desalting gel filtration
-
recombinant enzyme
recombinant enzyme from Escherichia coli strain BL21(DE3) by heat treatment at 70°C for 3 h, anion exchange chromatography, dialysis, and ultrafiltration
recombinant His-tagged enzyme from Echerichia coli strain Rosetta (DE3) pLysS by nickel affinty chromatography and gel filtration
recombinant His-tagged wild-type and mutant enzymes from Echerichia coli strain Rosetta (DE3) pLysS by nickel affinty chromatography and gel filtration
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli strain BL21 (DE3) codon plus-RIPL by heat treatment at 90°C for 10 min, nickel affinity chromatography, dialysis, gel filtration, and ultrafiltration
separation of the two isozymes using Matrex Gel Red A affinity chromatography
-
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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
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
-
gene hom, DNA and amino acid sequence determination and analysis, expression in the auxotroph mutant Escherichia coli CGSC 5075
gene hom, recombinant expression of His-tagged enzyme in Echerichia coli strain Rosetta (DE3) pLysS
gene hom, recombinant expression of His-tagged wild-type and mutant enzymes in Echerichia coli strain Rosetta (DE3) pLysS
gene hom, recombinant overexpression in Escherichia coli strain BL21(DE3)
gene hom1, recombinant expression of wild-type and mutant enzymes in Escherichia coli strain BL21(DE3), recombinant overexpression of constructs comprising the enzyme with homoserine kinase, aspartate kinase, acetohydroxy acid synthase, or threonine dehydratase, overview
gene HOM6, DNA and amino acid sequence determination and analysis from the strain SC5314 genome, sequence comparison, reintegration of the gene encoding the wild-type enzyme into HOM6-deletion strains
gene PH1075, recombinant expression of His-tagged wild-type and mutant enzymes in Escherichia coli strain BL21 (DE3) codon plus-RIPL
recombinant expression of wild-type and mutant enzymes in Escherichia coli strain BL21
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
strongly repressed by L-methionine
strongly repressed by L-threonine
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RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
pharmacology
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enzyme is a target for inhibitor design for construction of antimicrobial agents
synthesis
additional information
drug development
the enzyme might be a good target for anti-fungal drug development
drug development
Candida albicans SC5314 / ATCC MYA-2876
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the enzyme might be a good target for anti-fungal drug development
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
synthesis
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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
additional information
HOM6 deletion reduces Candida albicans cell adhesion to polystyrene, which is a common plastic used in many medical devices
additional information
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HOM6 deletion reduces Candida albicans cell adhesion to polystyrene, which is a common plastic used in many medical devices
additional information
Candida albicans SC5314 / ATCC MYA-2876
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HOM6 deletion reduces Candida albicans cell adhesion to polystyrene, which is a common plastic used in many medical devices
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Sainis, J.K.; Mayne, R.G.; Wallsgrove, R.M.; Lea, P.J.; Miflin, B.J.
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Hordeum vulgare, Pisum sativum
brenda
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Use of monoclonal antibodies for the purification and characterization of the threonine-sensitive isozyme of maize homoserine dehydrogenase
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Zea mays
brenda
Krishnaswamy, S.; Bryan, J.K.
Ligand-induced interconversions of maize homoserine dehydrogenase among different states
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222
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1983
Zea mays
brenda
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Zea mays
brenda
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Comparison of sensitive and desensitized forms of maize homoserine dehydrogenase
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Zea mays
brenda
Wedler, F.C.; Ley, B.W.
Kinetic and regulatory mechanisms for (Escherichia coli) homoserine dehydrogenase-I
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brenda
Grego, S.; Tricoli, D.; Di Marco, G.
Comparison of homoserine dehydrogenase from different plant sources
Phytochemistry
19
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1980
Ricinus communis, Pisum sativum, Triticum aestivum
-
brenda
Epstein, C.C.; Datta, P.
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82
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Rhodospirillum rubrum
brenda
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Reaction of Tris with aldehydes. Effect of Tris on reactions catalyzed by homoserine dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase
Biochim. Biophys. Acta
445
525-536
1976
Escherichia coli
brenda
Aarnes, H.; Rognes, S.E.
Threonine-sensitive aspartate kinase and homoserine dehydrogenase from Pisum sativum
Phytochemistry
13
2717-2724
1974
Pisum sativum
-
brenda
Cavari, B.Z.; Grossowicz, N.
Properties of homoserine dehydrogenase in a thermophilic bacterium
Biochim. Biophys. Acta
302
183-190
1973
Thermophilic bacterium
brenda
Saiki, T.; Shinshi, H.; Arima, K.
Studies on homoserine dehydrogenase from an extreme thermophile, Thermus flavus AT-62. Partial purification and properties
J. Biochem.
74
1239-1248
1973
Thermus thermophilus
brenda
Morbach, S.; Kelle, R.; Winkels, S.; Sahm, H.; Eggeling, L.
Engineering the homoserine dehydrogenase and threonine dehydratase control points to analyse flux towards L-isoleucine in Corynebacterium glutamicum
Appl. Microbiol. Biotechnol.
45
612-620
1996
Corynebacterium glutamicum
-
brenda
Pavagi, S.; Kochhar, S.; Kochhar, V.K.; Sane, P.V.
Purification and characterization of homoserine dehydrogenase from spinach leaves
Biochem. Mol. Biol. Int.
36
649-658
1995
Spinacia oleracea
brenda
DeLaBarre, B.; Thompson, P.R.; Wright, G.D.; Berghuis, A.M.
Crystal structures of homoserine dehydrogenase suggest a novel catalytic mechanism for oxidoreductases
Nat. Struct. Biol.
7
238-244
2000
Saccharomyces cerevisiae (P31116), Saccharomyces cerevisiae
brenda
Yamaki, H.; Yamaguchi, M.; Imamura, H.; Suzuki, H.; Nishimura, T.; Saito, H.; Yamaguchi, H.
The mechanism of antifungal action of (S)-2-amino-4-oxo-5-hydroxypentanoic acid, RI-331: The inhibition of homoserine dehydrogenase in Saccharomyces cerevisiae
Biochem. Biophys. Res. Commun.
168
837-843
1990
Saccharomyces cerevisiae
brenda
Hama, H.; Kayahara, T.; Tsuda, M.; Tsuchiya, T.
Inhibition of homoserine dehydrogenase I by L-serine in Escherichia coli
J. Biochem.
109
604-608
1991
Escherichia coli
brenda
Yumoto, N.; Kawata, Y.; Noda, S.; Tokushige, M.
Rapid purification and characterization of homoserine dehydrogenase from Saccharomyces cerevisiae
Arch. Biochem. Biophys.
285
270-275
1991
Saccharomyces cerevisiae
brenda
Angeles, T.S.; Viola, R.E.
The kinetic mechanism of the bifunctional enzyme aspartokinase - Homoserine dehydrogenase I from Escherichia coli
Arch. Biochem. Biophys.
283
96-101
1990
Escherichia coli
brenda
Jacques, S.L.; Ejim, L.J.; Wright, G.D.
Homoserine dehydrogenase from Saccharomyces cerevisiae: kinetic mechanism and stereochemistry of hydride transfer
Biochim. Biophys. Acta
1544
42-54
2001
Saccharomyces cerevisiae
brenda
Jacques, S.L.; Nieman, C.; Bareich, D.; Broadhead, G.; Kinach, R.; Honek, J.F.; Wright, G.D.
Characterization of yeast homoserine dehydrogenase, an antifungal target: the invariant histidine 309 is important for enzyme integrity
Biochim. Biophys. Acta
1544
28-41
2001
Saccharomyces cerevisiae (P31116), Saccharomyces cerevisiae
brenda
Omori, K.; Komatsubara, S.
Role of serine 352 in the allosteric response of Serratia marcescens aspartokinase I-homoserine dehydrogenase I analyzed by using site-directed mutagenesis
J. Bacteriol.
175
959-965
1993
Serratia marcescens
brenda
Paris, S.; Wessel, P.M.; Dumas, R.
Overproduction, purification, and characterization of recombinant bifunctional threonine-sensitive aspartate kinase-homoserine dehydrogenase from Arabidopsis thaliana
Protein Expr. Purif.
24
105-110
2002
Arabidopsis thaliana (O81852), Arabidopsis thaliana
brenda
Paris, S.; Viemon, C.; Curien, G.; Dumas, R.
Mechanism of control of Arabidopsis thaliana aspartate kinase-homoserine dehydrogenase by threonine
J. Biol. Chem.
278
5361-5366
2003
Arabidopsis thaliana
brenda
James, C.L.; Viola, R.E.
Production and characterization of bifunctional enzymes. Domain swapping to produce new bifunctional enzymes in the aspartate pathway
Biochemistry
41
3720-3725
2002
Escherichia coli
brenda
Ejim, L.; Mirza, I.A.; Capone, C.; Nazi, I.; Jenkins, S.; Chee, G.L.; Berghuis, A.M.; Wright, G.D.
New phenolic inhibitors of yeast homoserine dehydrogenase
Bioorg. Med. Chem.
12
3825-3830
2004
Saccharomyces cerevisiae
brenda
Rognes, S.E.; Dewaele, E.; Aas, S.F.; Jacobs, M.; Frankard, V.
Transcriptional and biochemical regulation of a novel Arabidopsis thaliana bifunctional aspartate kinase-homoserine dehydrogenase gene isolated by functional complementation of a yeast hom6 mutant
Plant Mol. Biol.
51
281-294
2003
Arabidopsis thaliana, Saccharomyces cerevisiae
brenda
Curien, G.; Ravanel, S.; Robert, M.; Dumas, R.
Identification of six novel allosteric effectors of Arabidopsis thaliana aspartate kinase-homoserine dehydrogenase isoforms. Physiological context sets the specificity
J. Biol. Chem.
280
41178-41183
2005
Arabidopsis thaliana
brenda
Cahyanto, M.N.; Kawasaki, H.; Nagashio, M.; Fujiyama, K.; Seki, T.
Regulation of aspartokinase, aspartate semialdehyde dehydrogenase, dihydrodipicolinate synthase and dihydrodipicolinate reductase in Lactobacillus plantarum
Microbiology
152
105-112
2006
Lactiplantibacillus plantarum
brenda
Yilmaz, E.I.; Caydasi, A.K.; Ozcengiz, G.
Targeted disruption of homoserine dehydrogenase gene and its effect on cephamycin C production in Streptomyces clavuligerus
J. Ind. Microbiol. Biotechnol.
35
1-7
2008
Streptomyces clavuligerus (Q56R01), Streptomyces clavuligerus, Streptomyces clavuligerus NRRL 3585 (Q56R01)
brenda
Park, S.D.; Lee, J.Y.; Sim, S.Y.; Kim, Y.; Lee, H.S.
Characteristics of methionine production by an engineered Corynebacterium glutamicum strain
Metab. Eng.
9
327-336
2007
Corynebacterium glutamicum
brenda
Varisi, V.A.; Camargos, L.S.; Aguiar, L.F.; Christofoleti, R.M.; Medici, L.O.; Azevedo, R.A.
Lysine biosynthesis and nitrogen metabolism in quinoa (Chenopodium quinoa): study of enzymes and nitrogen-containing compounds
Plant Physiol. Biochem.
46
11-18
2008
Chenopodium quinoa
brenda
Brautaset, T.; Jakobsen, O.M.; Degnes, K.F.; Netzer, R.; Naerdal, I.; Krog, A.; Dillingham, R.; Flickinger, M.C.; Ellingsen, T.E.
Bacillus methanolicus pyruvate carboxylase and homoserine dehydrogenase I and II and their roles for L-lysine production from methanol at 50 degrees C
Appl. Microbiol. Biotechnol.
87
951-964
2010
Bacillus methanolicus (D8WXQ1), Bacillus methanolicus (D8WXQ2), Bacillus methanolicus, Bacillus methanolicus MGA3 (D8WXQ1), Bacillus methanolicus MGA3 (D8WXQ2), Bacillus methanolicus MGA3
brenda
Schroeder, A.C.; Zhu, C.; Yanamadala, S.R.; Cahoon, R.E.; Arkus, K.A.; Wachsstock, L.; Bleeke, J.; Krishnan, H.B.; Jez, J.M.
Threonine-insensitive homoserine dehydrogenase from soybean: genomic organization, kinetic mechanism, and in vivo activity
J. Biol. Chem.
285
827-834
2010
Glycine max (O63067), Glycine max (O65027), Glycine max (Q3S3F6), Glycine max
brenda
Dong, X.; Zhao, Y.; Zhao, J.; Wang, X.
Characterization of aspartate kinase and homoserine dehydrogenase from Corynebacterium glutamicum IWJ001 and systematic investigation of L-isoleucine biosynthesis
J. Ind. Microbiol. Biotechnol.
43
873-885
2016
Corynebacterium glutamicum (P08499), Corynebacterium glutamicum, Corynebacterium glutamicum IWJ001 (P08499), Corynebacterium glutamicum IWJ001
brenda
Chen, Z.; Rappert, S.; Zeng, A.P.
Rational design of allosteric regulation of homoserine dehydrogenase by a nonnatural inhibitor L-lysine
ACS Synth. Biol.
4
126-131
2015
Corynebacterium glutamicum (P08499), Corynebacterium glutamicum
brenda
Navratna, V.; Reddy, G.; Gopal, B.
Structural basis for the catalytic mechanism of homoserine dehydrogenase
Acta Crystallogr. Sect. D
71
1216-1225
2015
Staphylococcus aureus (A0A0H2WVX4), Staphylococcus aureus, Staphylococcus aureus COL (A0A0H2WVX4)
brenda
Navratna, V.; Gopal, B.
Crystallization and preliminary X-ray diffraction studies of Staphylococcus aureus homoserine dehydrogenase
Acta Crystallogr. Sect. F
69
1216-1219
2013
Staphylococcus aureus (A0A0H2WVX4), Staphylococcus aureus, Staphylococcus aureus COL (A0A0H2WVX4)
brenda
Tomonaga, Y.; Kaneko, R.; Goto, M.; Ohshima, T.; Yoshimune, K.
Structural insight into activation of homoserine dehydrogenase from the archaeon
Biochem. Biophys. Rep.
3
14-17
2015
Sulfurisphaera tokodaii (F9VNG5), Sulfurisphaera tokodaii DSM 16993 / JCM 10545 / NBRC 100140 / 7 (F9VNG5)
brenda
Zhan, D.; Wang, D.; Min, W.; Han, W.
Exploring the molecular basis for selective binding of homoserine dehydrogenase from Mycobacterium leprae TN toward inhibitors: a virtual screening study
Int. J. Mol. Sci.
15
1826-1841
2014
Mycobacterium leprae (P46806), Mycobacterium leprae TN (P46806), Mycobacterium leprae TN
brenda
Tsai, P.W.; Chien, C.Y.; Yeh, Y.C.; Tung, L.; Chen, H.F.; Chang, T.H.; Lan, C.Y.
Candida albicans Hom6 is a homoserine dehydrogenase involved in protein synthesis and cell adhesion
J. Microbiol. Immunol. Infect.
50
863-871
2017
Candida albicans (Q5AIA2), Candida albicans, Candida albicans SC5314 / ATCC MYA-2876 (Q5AIA2)
brenda
Hayashi, J.; Inoue, S.; Kim, K.; Yoneda, K.; Kawarabayasi, Y.; Ohshima, T.; Sakuraba, H.
Crystal structures of a hyperthermophilic archaeal homoserine dehydrogenase suggest a novel cofactor binding mode for oxidoreductases
Sci. Rep.
5
11674
2015
Pyrococcus horikoshii (O58802), Pyrococcus horikoshii ATCC 700860 (O58802)
brenda
Shen, S.; Zhu, Y.; Fang, L.; Xu, J.
Heterologous expression and characterization of L200F/D215K mutant of homoserine dehydrogenase from Corynebacterium pekinense AS1.299
Wei Sheng Wu Xue Bao
54
1178-1184
2014
Corynebacterium pekinense, Corynebacterium pekinense AS1.299
brenda
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