Information on EC 2.7.1.39 - homoserine kinase

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

EC NUMBER
COMMENTARY
2.7.1.39
-
RECOMMENDED NAME
GeneOntology No.
homoserine kinase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
ATP + L-homoserine = ADP + O-phospho-L-homoserine
show the reaction diagram
ordered random mechanism with ATP preferentially binding before L-homoserine
-
ATP + L-homoserine = ADP + O-phospho-L-homoserine
show the reaction diagram
rapid equilibrium random bi bi mechanism
-
ATP + L-homoserine = ADP + O-phospho-L-homoserine
show the reaction diagram
the catalytic mechanism of the enzyme does not involve a catalytic base for activating the phosphoryl acceptor hydroxyl but instead is mediated via a transition state stabilization mechanism
Q58504
ATP + L-homoserine = ADP + O-phospho-L-homoserine
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
phospho group transfer
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
Glycine, serine and threonine metabolism
-
Metabolic pathways
-
methionine biosynthesis II
-
Microbial metabolism in diverse environments
-
threonine biosynthesis from homoserine
-
SYSTEMATIC NAME
IUBMB Comments
ATP:L-homoserine O-phosphotransferase
-
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
homoserine kinase
Q8L7R2
-
homoserine kinase
-
-
homoserine kinase (phosphorylating)
-
-
-
-
HSK
-
-
-
-
kinase (phosphorylating), homoserine
-
-
-
-
kinase, homoserine (phosphorylating)
-
-
-
-
Thr1
-
gene name
Thr1
-
gene name
Thr1
-
gene name
-
CAS REGISTRY NUMBER
COMMENTARY
9026-58-8
-
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
-
deletion mutants show homoserine-mediated lethality
malfunction
-
homoserine kinase deletion mutants are attenuated in virulence and die rapidly upon threonine starvation and serum incubation
malfunction
-
homoserine kinase deletion mutants are extremely serum sensitive and hypersensitive to DNA-damaging agents
malfunction
-
deletion mutants show homoserine-mediated lethality
-
metabolism
-, Q8L7R2
downy mildew resistance is mediated by mutation of homoserine kinase: homoserine accumulation in the chloroplast triggers a novel form of downy mildew resistance
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + 4-hydroxynorvaline
ADP + 4-phospho-L-norvaline
show the reaction diagram
-
0.3% of the activity with L-homoserine
-
-
?
ATP + D-homoserine
ADP + O-phospho-D-homoserine
show the reaction diagram
-
32% of the turnover number with L-homoserine
-
-
?
ATP + L-2-amino-1,4-butanediol
ADP + ?
show the reaction diagram
-
7.9% of the turnover number with L-homoserine
-
-
?
ATP + L-2-amino-5-hydroxyvalerate
ADP + L-2-amino-5-phosphovalerate
show the reaction diagram
-
9.9% of the turnover number with L-homoserine
-
-
?
ATP + L-aspartate 4-semialdehyde
?
show the reaction diagram
-
8.2% of the turnover number with L-homoserine
-
-
?
ATP + L-aspartate 4-semialdehyde
?
show the reaction diagram
-
10% of the activity with L-homoserine
-
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
-
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
-
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
-
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
-
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
-
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
-
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
-
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
-
-
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
-
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
-
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
-
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-, Q9XEE0
-
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
-
-
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
-
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
-
-
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
-
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
-
-
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
-
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
-
-
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
-
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
-
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
Q58504
-
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
-
-
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
Q58504
fourth enzyme in the aspartate pathway of amino acid biosynthesis
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
enzyme in the aspartate pathway of amino acid biosynthesis
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
key enzyme in the aspartate pathway of amino acid biosynthesis in E. coli
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
the enzyme plays an important role in the regulation of the threonine biosynthesis
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
the enzyme is not involved in the regulation of methionine, threonine and isoleucine biosynthesis
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
enzyme of threonine biosynthesis
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-, Q9XEE0
formation of O-phospho-L-homoserine, a branch point intermediate in the pathways for Met and Thr in plants
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
the enzyme catalyzes a reaction common to synthesis of Thr, Ile and Met in plants
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
the enzyme catalyzes a reaction common to synthesis of Thr, Ile and Met in plants, the enzyme is a potential control point in the biosyntic pathway for Thr, Ile and Met
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
enzyme catalyzes an obligatory step of threonine biosynthesis
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
enzyme of L-Thr synthesis
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
involved in the biosynthesis of threonine
-
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
involved in the biosynthesis of threonine and isoleucine
-
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
involved in the biosynthesis of threonine, isoleucine, and methionine, substrate availability rather than enzyme level rate limiting for the reaction
-
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
-
-
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
Rhodospirillum rubrum S1
-
-, enzyme of L-Thr synthesis
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
-
-
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
-, involved in the biosynthesis of threonine
-
-
?
ATP + L-homoserine ethyl ester
ADP + O-phospho-L-homoserine ethyl ester
show the reaction diagram
-
74% of the turnover number with L-homoserine
-
-
?
ATP + L-homoserine isopropyl ester
ADP + O-phospho-L-homoserine isopropyl ester
show the reaction diagram
-
74% of the turnover number with L-homoserine
-
-
?
ATP + L-homoserine isubutyl ester
ADP + O-phospho-L-homoserine isobutyl ester
show the reaction diagram
-
84% of the turnover number with L-homoserine
-
-
?
ATP + L-homoserine methyl ester
ADP + O-phospho-L-homoserine methyl ester
show the reaction diagram
-
80% of the turnover number with L-homoserine
-
-
?
ATP + L-homoserine n-butyl ester
ADP + O-phospho-L-homoserine n-butyl ester
show the reaction diagram
-
160% of the turnover number with L-homoserine
-
-
?
ATP + L-homoserine n-propyl ester
ADP + O-phospho-L-homoserine n-propyl ester
show the reaction diagram
-
76% of the turnover number with L-homoserine
-
-
?
L-homoserine + ATP
O-phospho-L-homoserine + ADP
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
enzyme has inherent ATPase activity
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
Q58504
fourth enzyme in the aspartate pathway of amino acid biosynthesis
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
enzyme in the aspartate pathway of amino acid biosynthesis
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
key enzyme in the aspartate pathway of amino acid biosynthesis in E. coli
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
the enzyme plays an important role in the regulation of the threonine biosynthesis
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
the enzyme is not involved in the regulation of methionine, threonine and isoleucine biosynthesis
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
enzyme of threonine biosynthesis
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-, Q9XEE0
formation of O-phospho-L-homoserine, a branch point intermediate in the pathways for Met and Thr in plants
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
the enzyme catalyzes a reaction common to synthesis of Thr, Ile and Met in plants
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
the enzyme catalyzes a reaction common to synthesis of Thr, Ile and Met in plants, the enzyme is a potential control point in the biosyntic pathway for Thr, Ile and Met
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
enzyme catalyzes an obligatory step of threonine biosynthesis
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
enzyme of L-Thr synthesis
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
involved in the biosynthesis of threonine
-
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
involved in the biosynthesis of threonine and isoleucine
-
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
involved in the biosynthesis of threonine, isoleucine, and methionine, substrate availability rather than enzyme level rate limiting for the reaction
-
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
Rhodospirillum rubrum S1
-
enzyme of L-Thr synthesis
-
?
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
-
involved in the biosynthesis of threonine
-
-
?
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Co2+
-
divalent cation required, efficiency of activation in descending order: Mg2+, Mn2+, Zn2+, Co2+
Co2+
-
ineffective
K+
-
monovalent cation required, K+ or NH4+
K+
-
absolute requirement for monovalent cation. Km: 21 mM
K+
-
KCl stimulates, maximum activation at 0.2 M
K+
-
activates
K+
-
200 mM, enhances activity about twice
K+
-
requires 40 mM K+
Mg2+
-
divalent cation required, efficiency of activation in descending order: Mg2+, Mn2+, Zn2+, Co2+
Mg2+
-
absolute requirement for divalent cation, Mg2+ or Mn2+
Mg2+
-
required
Mg2+
-
absolute requirement, optimal activity between 10 mM and 20 mM
Mg2+
-
stimulates
Mg2+
-
required
Mn2+
-
divalent cation required, efficiency of activation in descending order: Mg2+, Mn2+, Zn2+, Co2+
Mn2+
-
absolute requirement for divalent cation, Mg2+ or Mn2+
Mn2+
-
can replace Mg2+ in stimulation
Mn2+
-
high requirement
Mn2+
-
requires 3 mM
Zn2+
-
divalent cation required, efficiency of activation in descending order: Mg2+, Mn2+, Zn2+, Co2+
Zn2+
-
ineffective
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(2Z)-2-cyano-N-(2,5-dibromophenyl)-3-hydroxybut-2-enamide
-
-
(p-hydroxyphenyl)-glyoxal
-
-
1,2-amino-5-hydroxyvalerate
-
substrate inhibition
-
1-(naphthalen-2-yl)prop-2-en-1-one
-
-
2-(2-methylpropyl)-6,7,8,9-tetrahydro-4H,5H-cyclohepta[4,5]thieno[2,3-d][1,3]oxazin-4-one
-
-
2-(3,4-dihydroxyphenyl)-3,6,7-trihydroxy-2,3-dihydro-4H-chromen-4-one
-
-
2-amino-3-(phosphonoethyl)thiopropionate
-
-
2-Amino-5-phosphonovalerate
-
-
2-amino-5-phosphovalerate
-
-
2-chloro-L-alanine
-
-
3-methyl-1-phenyl-6-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyridin-4-ol
-
-
4-hydroxy-3-[(4-hydroxy-2-oxo-3,8a-dihydro-2H-chromen-3-yl)methyl]-2H-chromen-2-one
-
-
5'-adenylylimidodiphosphate
-
-
6-hydroxy-DL-Lys
-
5 mM, 92% inhibition
alpha-amino-beta-hydroxy valeric acid
-
-
diethyl dicarbonate
-
-
L-2-aminobutyrate
-
-
L-2-aminobutyric acid
-
40 mM, 50% inhibition
L-alpha-Aminobutyric acid
-
-
L-Arg
-
10 mM, 13% inhibition
L-aspartate
-
slight
L-aspartate semialdehyde
-
mixed inhibition versus L-homoserine and ATP
L-Cys
-
10 mM, 25% inhibition
L-Glutamic acid
-
-
L-homocysteine
-
-
L-homoserine
-
above 0.75 mM
L-homoserine
-
-
L-homoserine
-
substrate inhibition
L-homoserine alpha-methyl ester
-
substrate inhibition
L-homoserine ethyl ester
-
unlike the wild-type enzyme the mutant enzyme H202L is inhibited
L-homoserine isopropyl ester
-
unlike the wild-type enzyme the mutant enzyme H202L is inhibited
L-homoserine n-propyl ester
-
unlike the wild-type enzyme the mutant enzyme H202L is inhibited
L-Ile
-
7.5 mM, 90% inhibition
L-Ile
-
no inhibition with the D-isomer
L-Leu
-
10 mM, 20% inhibition
L-Lys
-
10 mM, 35% inhibition
L-Met
-
10 mM, 17% inhibition
L-norvaline
-
-
L-Orn
-
10 mM, 64% inhibition
L-Ser
-
10 mM, 10% inhibition
L-Thr
-
10 mM, 18% inhibition
L-Thr
-
8.1 mM, 50% inhibition
L-Thr
-
half-maximal inhibition at 10 mM
L-Thr
-
competitive to the substrate L-homoserine
L-Thr
-
substrate inhibition
L-Val
-
16 mM, 86% inhibition
O-Phospho-DL-homoserine
-
10 mM, 91% inhibition
O-phospho-L-serine
-
-
phosphohomoserine
-
inhibits phosphorylation of L-homoserine
pyridoxal 5'-phosphate
-
-
S-adenosyl-L-methionine
-
10 mM, 92% inhibition
S-adenosyl-L-methionine
-
-
S-adenosyl-L-methionine
-
10 mM, 26% inhibition
additional information
-
no feedback inhibition by Thr, Met or Ile
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
L-Cys
-
slight activation
NH4+
-
monovalent cation required, K+ or NH4+
NH4+
-
100 mM NH4Cl results in 35% of the activation compared to 100 mM K+
NH4+
-
30% of the activity obtained with 0.5 M K+
NH4+
-
not essential, but stimulates
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
3.8
-
4-hydroxynorvaline
-
pH 7.8
0.0676
-
ATP
-
in 50 mM HEPES, pH 7.5, 40 mM KCl, 10 mM MgCl2, at 37C
0.11
-
ATP
-
mutant enzyme H202L
0.11
-
ATP
-
method: isothermal titration calometry
0.13
-
ATP
-
mutant enzyme R234H; wild-type enzyme
0.15
-
ATP
-
mutant enzyme H205Q
0.21
-
ATP
-
mutant enzyme R234L
0.27
-
ATP
-
pH 7.5, 30C
0.3
-
ATP
-
pH 7.8, 27C
0.44
-
ATP
-
pH 8, 28C
0.49
-
ATP
-
mutant enzyme H139L
0.55
-
ATP
-
pH 7.8, 37C
0.6
-
ATP
-
pH 7.5, 30C
0.88
-
ATP
-
mutant enzyme R234C
1.2
-
ATP
-
pH 7.5, 30C
2.7
-
ATP
-
pH 8.5
31.8
-
D-homoserine
-
wild-type enzyme
0.087
-
homoserine
-
method: isothermal titration calometry
11.6
-
L-2-amino-1,4-butanediol
-
wild-type enzyme
1.1
-
L-2-amino-5-hydroxyvalerate
-
wild-type enzyme
0.28
-
L-aspartate beta-semialdehyde
-
wild-type enzyme
0.58
-
L-aspartate semialdehyde
-
pH 7.8
0.11
-
L-homoserine
-
mutant enzyme H202L
0.13
-
L-homoserine
-
mutant enzyme R234H
0.14
-
L-homoserine
-
wild-type enzyme
0.15
-
L-homoserine
-
pH 7.8
0.24
-
L-homoserine
-
-
0.24
-
L-homoserine
-
pH 7.8, 37C
0.25
-
L-homoserine
-
pH 7.5, 30C
0.3
-
L-homoserine
-
pH 7.8, 27C
0.4
-
L-homoserine
-
-
0.4
-
L-homoserine
-
-
0.463
-
L-homoserine
-
in 50 mM HEPES, pH 7.5, 40 mM KCl, 10 mM MgCl2, at 37C
0.52
-
L-homoserine
-
pH 7.5, 30C
0.77
-
L-homoserine
-
pH 7.5, 30C
2.5
-
L-homoserine
-
mutant enzyme H139L
3
-
L-homoserine
-
pH 8, 28C
3.7
-
L-homoserine
-
mutant enzyme H205Q
6.2
-
L-homoserine
-
mutant enzyme R234H
6.7
-
L-homoserine
-
pH 8.5
6.9
-
L-homoserine
-
wild-type enzyme
8.5
-
L-homoserine
-
mutant enzyme R234C
40.1
-
L-homoserine
-
mutant enzyme R234L
58.2
-
L-homoserine
-
mutant enzyme H202L
1.9
-
L-homoserine ethyl ester
-
wild-type enzyme
6.9
-
L-homoserine isobutyl ester
-
wild-type enzyme
1.2
-
L-homoserine isopropyl ester
-
wild-type enzyme
4.9
-
L-homoserine methyl ester
-
wild-type enzyme
5.8
-
L-homoserine n-butyl ester
-
wild-type enzyme
3.5
-
L-homoserine n-propyl ester
-
wild-type enzyme
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
14.2
-
ATP
-
in 50 mM HEPES, pH 7.5, 40 mM KCl, 10 mM MgCl2, at 37C
40.8
-
ATP
-
pH 7.5, 30C
3.3
-
D-homoserine
-
wild-type enzyme
2
-
L-2-amino-1,4-butanediol
-
wild-type enzyme
2.5
-
L-2-amino-5-hydroxyvalerate
-
wild-type enzyme
2.1
-
L-aspartate beta-semialdehyde
-
wild-type enzyme
0.2
-
L-homoserine
-
mutant R234L
0.75
-
L-homoserine
-
method: isothermal titration calometry
9.1
-
L-homoserine
-
mutant H202L
11.2
-
L-homoserine
-
in 50 mM HEPES, pH 7.5, 40 mM KCl, 10 mM MgCl2, at 37C
18.3
-
L-homoserine
-
wild-type enzyme
40.2
-
L-homoserine
-
pH 7.5, 30C
0.007
-
L-homoserine butyl ester
-
mutant R234L
2.5
-
L-homoserine butyl ester
-
mutant H202L
0.021
-
L-homoserine ethyl ester
-
mutant R234L
4.1
-
L-homoserine ethyl ester
-
mutant H202L
13.6
-
L-homoserine ethyl ester
-
wild-type enzyme
16.4
-
L-homoserine isobutyl ester
-
wild-type enzyme
13.6
-
L-homoserine isopropyl ester
-
wild-type enzyme
0.018
-
L-homoserine methyl ester
-
mutant R234L
5.4
-
L-homoserine methyl ester
-
mutant H202L
14.7
-
L-homoserine methyl ester
-
wild-type enzyme
29.1
-
L-homoserine n-butyl ester
-
wild-type enzyme
14
-
L-homoserine n-propyl ester
-
wild-type enzyme
0.0111
-
L-homoserine propyl ester
-
mutant R234L
2.7
-
L-homoserine propyl ester
-
mutant H202L
kcat/KM VALUE [1/mMs-1]
kcat/KM VALUE [1/mMs-1] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
210
-
ATP
-
in 50 mM HEPES, pH 7.5, 40 mM KCl, 10 mM MgCl2, at 37C
22040
24.1
-
L-homoserine
-
in 50 mM HEPES, pH 7.5, 40 mM KCl, 10 mM MgCl2, at 37C
12256
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.012
-
(2Z)-2-cyano-N-(2,5-dibromophenyl)-3-hydroxybut-2-enamide
-
in 50 mM HEPES, pH 7.5, 40 mM KCl, 10 mM MgCl2, at 37C
0.032
-
1-(naphthalen-2-yl)prop-2-en-1-one
-
in 50 mM HEPES, pH 7.5, 40 mM KCl, 10 mM MgCl2, at 37C
0.0358
-
2-(2-methylpropyl)-6,7,8,9-tetrahydro-4H,5H-cyclohepta[4,5]thieno[2,3-d][1,3]oxazin-4-one
-
in 50 mM HEPES, pH 7.5, 40 mM KCl, 10 mM MgCl2, at 37C
0.0271
-
2-(3,4-dihydroxyphenyl)-3,6,7-trihydroxy-2,3-dihydro-4H-chromen-4-one
-
in 50 mM HEPES, pH 7.5, 40 mM KCl, 10 mM MgCl2, at 37C
0.3
-
2-amino-3-(phosphonoethyl)thiopropionate
-
wild-type enzyme
10.4
-
2-amino-5-phosphovalerate
-
-
15
-
2-chloro-L-alanine
-
pH 7.8, 37C
0.0086
-
3-methyl-1-phenyl-6-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyridin-4-ol
-
in 50 mM HEPES, pH 7.5, 40 mM KCl, 10 mM MgCl2, at 37C
0.00046
-
4-hydroxy-3-[(4-hydroxy-2-oxo-3,8a-dihydro-2H-chromen-3-yl)methyl]-2H-chromen-2-one
-
in 50 mM HEPES, pH 7.5, 40 mM KCl, 10 mM MgCl2, at 37C
0.9
-
5'-adenylylimidodiphosphate
-
pH 7.4
0.4
-
L-2-aminobutyrate
-
pH 7.8, 37C
0.15
-
L-alpha-Aminobutyric acid
-
-
0.46
-
L-Cys
-
wild-type enzyme
1
-
L-Cys
-
pH 7.8, 37C
0.2
0.5
L-Glutamic acid
-
wild-type enzyme
4
-
L-homocysteine
-
pH 7.8, 37C
0.1
-
L-homoserine
-
in 20% DMSO
2
-
L-homoserine
-
pH 7.6
2
-
L-homoserine
-
pH 7.5, 30C
3
-
L-homoserine
-
aqueous sulution, pH 8
0.9
-
L-Ile
-
pH 8.5
4.5
-
L-Ile
-
pH 7.8, 37C
35
-
L-Met
-
pH 7.8, 37C
0.2
0.5
L-norvaline
-
wild-type enzyme
4.3
-
L-Orn
-
pH 8.5
27
-
L-Ser
-
pH 7.8, 37C
0.3
-
L-Thr
-
wild-type enzyme
0.6
-
L-Thr
-
pH 7.8, 37C
1
-
L-Thr
-
pH 7.8, 27C
0.9
-
L-Val
-
pH 8.5
2.7
-
O-phospho-L-serine
-
-
10
-
L-Val
-
pH 7.8, 37C
additional information
-
additional information
-
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.024
-
-
-
3.09
-
-
L-homoserine-dependent ADP synthesis assay at pH 8.5 and 37C
additional information
-
-
-
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7.4
-
-
Tris buffer
8
-
-
wild-type enzyme
8.5
-
-
-
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
8.1
9
-
the enzyme shows good activity in Tris-HCl buffer from pH 8.1 to pH 9.0
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
soluble in stromal fraction
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Agrobacterium tumefaciens (strain C58 / ATCC 33970)
Cytophaga hutchinsonii (strain ATCC 33406 / NCIMB 9469)
Listeria monocytogenes serovar 1/2a (strain ATCC BAA-679 / EGD-e)
Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440)
Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440)
Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440)
Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440)
Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440)
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
55000
-
-
gel filtration
60000
-
-
gel filtration
73000
-
-
gel filtration
75000
-
-
gel filtration
145000
-
-
gel filtration
additional information
-
-
2 peaks of MW 120000 Da and 240000 Da are detected by gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
dimer
-
2 * 36000, SDS-PAGE
dimer
-
2 * 40000, SDS-PAGE
dimer
-
2 * 29000, SDS-PAGE
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
crystals are grown by the hanging drop vapor diffusion method; crystal structure of the enzyme with ADP reveals a novel nucleotide binding fold. The N-terminal domain contains an unusual left-handed beta,alpha,beta unit, while the C-terminal domain has a central alpha-beta plait fold with an insertion of four helices
-
crystals are grown by the hanging drop vapor diffusion method; the enzyme ternary complexes with its amino acid substrate and ATP analogues determined by X-ray crystallography
Q58504
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
50
-
-
stable up to in absence of ligands
57
-
-
half-life is 10 min in absence of L-Thr ot L-homoserine
additional information
-
-
homoserine and MgATP2- protect against heat inactivation
additional information
-
-
homoserine and MgATP2- do not protect against heat inactivation
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
enzyme stored with 3 mM ATP loses 50% of its activity after two freezing cycles. In presence of 50% v/v glycerol the enzyme loses 50% of its activity after 10 cycles. In the basic storage buffer, the enzyme loses 80% of its activity after a single freeze-thaw cycle
-
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-25C, purified enzyme is stable for at least 1 month
-
-80C, 20 mM HEPES, pH 8.0, 10% glycerol, storage of purified enzyme
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
partial
-
Ni-NTA column chromatography, gel filtration
-
recombinant enzyme using His-tag
-
partial purification from host strain
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expression of a His-tagged construct in Escherichia coli
-
His-tag, expressed in Escherichia coli
-, Q8L7R2
overexpressed in Arabidopsis thaliana
-
expression in potato
-
the combination of pTZ19u(ThrB) and the BL21(DE3) cell line is the best expression system with nearly 160 mg of enzyme produced in 4 liters of growth medium
-
gene thrH is expressed in Escherichia coli
-
expressed as His-tag fusion protein in Escherichia coli BL21(DE3)
-
expressed in Escherichia coli BL21(DE3) cells
-
expressed in Escherichia coli
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
H139L
-
mutant enzyme with diminished kinase activity and ATPase activity 150fold greater than that of the wild-type enzyme
H202L
-
Km-value for L-homoserine and ATP remain unchanged, the Ki-value for substrate inhibition by L-homoserine increases about 8fold, the turnover-number decreases by 50%,unlike the wild-type enzyme the L-homoserine ethyl, isopropyl, and n-propyl esters show substrate inhibition
R234C
-
no observable homoserine kinase activity, the ATPase activity is nearly 20 times that of the wild-type enzyme at pH 8.0. 7fold increase in Km-value for ATP. Mutant enzyme is sensitive to heat treatment and begins to precipitate at 55C
R234H
-
mutant enzyme has a diminished kinase activity, 0.4% of that of the wild-type enzyme, and an enhanced ATPase activity, Km-values for both substrates are unchanged
R234L
-
Km-value for L-homoserine increases nearly 300fold, the turnover-number decreases by 90fold compared to the wild-type enzyme. Less than a 2fold change in Km for ATP, the inherent ATPase activity increases by 3fold. The mutant enzyme has turnover-numbers for homoserine esters that are only 10% that of homoserine, but has higher affinity for the esters than for L-homoserine itself. L-Cys, a strong inhibitor of the wild-type enzyme, is 50fold less effective as inhibitor of the mutant enzyme. L-Thr no longer inhibits the mutant enzyme. Unlike the wild-type enzyme, addition of 10 mM L-homoserine to the mutant enzyme has no protective effect on the number of arginyl residues titrated with (p-hydroxyphenyl)glyoxal
additional information
-, Q8L7R2
six independent mutants of homoserine kinase (E46K, G118R, G180D, G202R, M241I, and A267V) are analyzed: 0-10% of wild-type activity
additional information
-
gene is essential for growth in rich media, when ammonium is the nitrogen source, or when threonine is supplied as an amino acid instead of a dipeptide. the severity of the growth defect associated with THR1 repression increases with increasing incubation temperature
H205Q
-
Km-value for ATP remains unchanged, ATPase activity is within a factor 2 of the wild-type enzyme, the kinase activity is less than 0.03% that of the wild-type enzyme
additional information
-
expression in Solanum tuberosum plant with targeting to chloroplast and cytosol. Both approaches result in up to 11fold increase in total enzyme activity. Transgenic plants exhibit reduced homoserine levels while methionine and threonine do not accumulate significantly. Plants with elevated levels of cytosolic enzyme exhibit a reduction in transcript levels of the endogenous homoserine kinase, as well as of threonine synthase, cystathionine beta-lyase, and methionine synthase. In all plants, cystathionine gamma-synthase expression remains unchanged, while S-adenosylmethionine synthetase expression increases. Excess of plastidial localized homoserine kinase does not influence the de novo synthesis of methionine and threonine
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
agriculture
-
expression of Escherichia coli homoserine kinase in Solanum tuberosum plants with targeting to chloroplast and cytosol. Both approaches result in up to 11fold increase in total enzyme activity. Transgenic plants exhibit reduced homoserine levels while methionine and threonine do not accumulate significantly. Plants with elevated levels of cytosolic enzyme exhibit a reduction in transcript levels of the endogenous homoserine kinase, as well as of threonine synthase, cystathionine beta-lyase, and methionine synthase. In all plants, cystathionine gamma-synthase expression remains unchanged, while S-adenosylmethionine synthetase expression increases. Excess of plastidial localized homoserine kinase does not influence the de novo synthesis of methionine and threonine
medicine
-
potential target for antibiotics due to the fact, that the pathway is not found in mammals