Information on EC 2.7.1.39 - homoserine kinase

New: Word Map on EC 2.7.1.39
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Mark a special word or phrase in this record:
Search Reference ID:
Select one or more organisms in this record:
Show additional data
Do not include text mining results
Include (text mining) results (more...)
Include results (AMENDA + additional results, but less precise; more...)


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

EC NUMBER
COMMENTARY hide
2.7.1.39
-
RECOMMENDED NAME
GeneOntology No.
homoserine kinase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + L-homoserine = ADP + O-phospho-L-homoserine
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phospho group transfer
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Biosynthesis of secondary metabolites
-
-
Glycine, serine and threonine metabolism
-
-
L-methionine biosynthesis II
-
-
L-threonine biosynthesis
-
-
Metabolic pathways
-
-
Microbial metabolism in diverse environments
-
-
threonine metabolism
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP:L-homoserine O-phosphotransferase
-
CAS REGISTRY NUMBER
COMMENTARY hide
9026-58-8
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
gene is essential for growth
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
L. cv. Pillert Fenomen
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
strain S1
-
-
Manually annotated by BRENDA team
strain S1
-
-
Manually annotated by BRENDA team
strain SK36
-
-
Manually annotated by BRENDA team
strain SK36
-
-
Manually annotated by BRENDA team
strain NRRL 5331
-
-
Manually annotated by BRENDA team
strain NRRL 5331
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
-
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
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
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
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
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
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + L-homoserine
ADP + O-phospho-L-homoserine
show the reaction diagram
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(2Z)-2-cyano-N-(2,5-dibromophenyl)-3-hydroxybut-2-enamide
-
-
(4R)-4-hydroxypentan-2-one
-
-
(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-Glutamic acid
-
-
L-homocysteine
-
-
L-homoserine
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-Leu
-
10 mM, 20% inhibition
L-Lys
-
10 mM, 35% inhibition
L-norvaline
-
-
L-Orn
-
10 mM, 64% 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
additional information
-
no feedback inhibition by Thr, Met or Ile
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
L-Cys
-
slight activation
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
3.8
4-hydroxynorvaline
-
pH 7.8
0.0676 - 2.7
ATP
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 - 58.2
L-homoserine
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]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
14.2 - 40.8
ATP
3.3
D-homoserine
Escherichia coli
-
wild-type enzyme
2
L-2-amino-1,4-butanediol
Escherichia coli
-
wild-type enzyme
2.5
L-2-amino-5-hydroxyvalerate
Escherichia coli
-
wild-type enzyme
2.1
L-aspartate beta-semialdehyde
Escherichia coli
-
wild-type enzyme
0.2 - 40.2
L-homoserine
0.007 - 2.5
L-homoserine butyl ester
0.021 - 13.6
L-homoserine ethyl ester
16.4
L-homoserine isobutyl ester
Escherichia coli
-
wild-type enzyme
13.6
L-homoserine isopropyl ester
Escherichia coli
-
wild-type enzyme
0.018 - 14.7
L-homoserine methyl ester
29.1
L-homoserine n-butyl ester
Escherichia coli
-
wild-type enzyme
14
L-homoserine n-propyl ester
Escherichia coli
-
wild-type enzyme
0.0111 - 2.7
L-homoserine propyl ester
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
210
ATP
Schizosaccharomyces pombe
-
in 50 mM HEPES, pH 7.5, 40 mM KCl, 10 mM MgCl2, at 37C
4
24.1
L-homoserine
Schizosaccharomyces pombe
-
in 50 mM HEPES, pH 7.5, 40 mM KCl, 10 mM MgCl2, at 37C
345
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
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
0.2 - 0.5
(4R)-4-hydroxypentan-2-one
-
wild-type enzyme
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 - 1
L-Cys
0.2 - 0.5
L-Glutamic acid
-
wild-type enzyme
4
L-homocysteine
-
pH 7.8, 37C
0.1 - 3
L-homoserine
0.9 - 4.5
L-Ile
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 - 1
L-Thr
0.9 - 10
L-Val
2.7
O-phospho-L-serine
-
-
additional information
additional information
-
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.024
-
-
3.09
-
L-homoserine-dependent ADP synthesis assay at pH 8.5 and 37C
additional information
-
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6 - 8.5
-
-
7.4
-
Tris buffer
8.3 - 9
-
-
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
8.1 - 9
-
the enzyme shows good activity in Tris-HCl buffer from pH 8.1 to pH 9.0
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
green
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
soluble in stromal fraction
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
UNIPROT
Agrobacterium fabrum (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)
Yersinia pestis bv. Antiqua (strain Nepal516)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
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
COMMENTARY hide
LITERATURE
Crystallization/COMMENTARY
ORGANISM
UNIPROT
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
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
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
GENERAL STABILITY
ORGANISM
UNIPROT
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
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
LITERATURE
Ni-NTA column chromatography, gel filtration
-
partial
partial purification from host strain
-
recombinant enzyme using His-tag
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed as His-tag fusion protein in Escherichia coli BL21(DE3)
-
expressed in Escherichia coli
-
expressed in Escherichia coli BL21(DE3) cells
-
expression in potato
-
expression of a His-tagged construct in Escherichia coli
-
gene thrH is expressed in Escherichia coli
-
His-tag, expressed in Escherichia coli
-
overexpressed in Arabidopsis thaliana
-
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
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
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
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
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
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
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
Show AA Sequence (8579 entries)
Longer loading times are possible. Please use the Sequence Search for a certain query.