Information on EC 2.7.1.36 - mevalonate kinase

New: Word Map on EC 2.7.1.36
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
2.7.1.36
-
RECOMMENDED NAME
GeneOntology No.
mevalonate kinase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + (R)-mevalonate = ADP + (R)-5-phosphomevalonate
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phospho group transfer
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Biosynthesis of antibiotics
-
-
Biosynthesis of secondary metabolites
-
-
isoprene biosynthesis II (engineered)
-
-
Metabolic pathways
-
-
mevalonate metabolism
-
-
mevalonate pathway I
-
-
mevalonate pathway II (archaea)
-
-
Terpenoid backbone biosynthesis
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP:(R)-mevalonate 5-phosphotransferase
CTP, GTP and UTP can also act as donors.
CAS REGISTRY NUMBER
COMMENTARY hide
9026-52-2
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
Citrus sp.
orange
-
-
Manually annotated by BRENDA team
pumpkin
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
-
mutations in the mevalonate kinase gene cause the hyperimmunoglobulin D syndrome, HIDS, an autosomal recessive autoinflammatory disease
metabolism
additional information
-
mevalonate kinase and Rho kinase are involved in regulation of BMP-2 mRNA expression, inhibition of both enzymes in osteoblastic MC3T3-E1 cells upregulates BMP-2 mRNA expression
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
adenosine 5'-O-(1-thio-triphosphate) + mevalonate
adenosine 5'-O-(1-thio-diphosphate) + 5-phosphomevalonate
show the reaction diagram
-
40% of activity with ATP in the presence of 2 mM Mg2+
-
-
adenosine 5'-O-(2-thio-triphosphate) + mevalonate
adenosine 5'-O-(2-thio-diphosphate) + 5-phosphomevalonate
show the reaction diagram
-
54% of activity with ATP in the presence of 2 mM Mg2+
-
-
adenosine 5'-O-(3-thio-triphosphate) + mevalonate
adenosine 5'-O-(3-thio-diphosphate) + 5-phosphomevalonate
show the reaction diagram
-
4% of activity with ATP in the presence of 2 mM Mg2+
-
-
ADP + mevalonate
?
show the reaction diagram
ATP + (R)-mevalonate
ADP + (R)-5-phosphomevalonate
show the reaction diagram
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
CTP + (R)-mevalonate
CDP + (R)-5-phosphomevalonate
show the reaction diagram
-
-
-
-
?
CTP + mevalonate
CDP + phosphomevalonate
show the reaction diagram
dATP + mevalonate
dADP + phosphomevalonate
show the reaction diagram
-
67% of the activity with ATP
-
?
dCTP + mevalonate
dCDP + phosphomevalonate
show the reaction diagram
-
17% of the activity with ATP
-
?
dGTP + mevalonate
dGDP + phosphomevalonate
show the reaction diagram
-
17% of the activity with ATP
-
?
GTP + (R)-mevalonate
GDP + (R)-5-phosphomevalonate
show the reaction diagram
-
-
-
-
?
GTP + mevalonate
GDP + phosphomevalonate
show the reaction diagram
ITP + (R)-mevalonate
IDP + (R)-5-phosphomevalonate
show the reaction diagram
-
-
-
-
?
ITP + mevalonate
IDP + phosphomevalonate
show the reaction diagram
TTP + (R)-mevalonate
TDP + (R)-5-phosphomevalonate
show the reaction diagram
-
-
-
-
?
TTP + mevalonate
TDP + phosphomevalonate
show the reaction diagram
-
15% of the activity with ATP
-
?
UTP + (R)-mevalonate
UDP + (R)-5-phosphomevalonate
show the reaction diagram
-
-
-
-
?
UTP + mevalonate
UDP + phosphomevalonate
show the reaction diagram
XTP + mevalonate
XDP + phosphomevalonate
show the reaction diagram
-
27% of the activity with ATP
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + (R)-mevalonate
ADP + (R)-5-phosphomevalonate
show the reaction diagram
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Sr2+
-
can partially replace Mg2+ in activation, 8% of activity with Mg2+ at 5 mM
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(3R),(5S)-P'-geranyl 3,5,8-trihydroxy-3-methyloctanate 8-diphosphate
-
-
(3S),(5R)-P'-geranyl 3,5,8-trihydroxy-3-methyloctanate 8-diphosphate
-
-
25-hydroxycholesterol
-
expression of mevalonate kinase is regulated by sterol response element-binding protein-1, which is sensitive to the cllular concentration of 25-hydroxycholesterol. Presence of 25-hydroxycholesterol inhibits mevalonate kinase expression and subsequently its binding to luteinizing hormone receptor mRNA
3,3-dimethylallyl diphosphate
-
-
5-diphosphomevalonate
-
allosteric and potent inhibition, the molecule functions as a partial bisubstrate analogue that elicits a ternary-complex-like form of the enzyme, binding structure, overview
5-phosphomevalonate
-
product inhibition, non-competitive with ATP and mevalonate
8-[[hydroxy(phosphonooxy)phosphoryl]oxy]octanoic acid
-
-
diphosphomevalonate
dolichol phosphate
-
-
estradiol
-
together with follicle-stimulating hormone, decreases mevalonate kinase mRNA levels, resulting in up-regulation of luteinizing hormone receptor mRNA that is inversely correlated to mevalonate kinase mRNA expression
Farnesol
-
-
farnesyl diphosphate
farnesyl thiodiphosphate
follicle-stimulating hormone
-
together with estradiol, decreases mevalonate kinase mRNA levels, resulting in up-regulation of luteinizing hormone receptor mRNA that is inversely correlated to mevalonate kinase mRNA expression
-
geranyl diphosphate
geranylgeranyl diphosphate
HgCl2
-
0.1 mM, 90% inhibition
isopentenyl diphosphate
-
-
lovastatin
-
inhibition of isoprenoid pathway, resulting in a dose-dependent reduction of amyloid formed compared with mononuclear cells that are exposed only to serum amyloid. The inhibitory effects of lovastatin are reversible by addition of farnesol but not geranylgeraniol. Farnesyl transferase inhibition also inhibits amyloidogenesis
mevalonate
mevalonate 5-diphosphate
-
-
mevalonate 5-phosphate
N-ethylmaleimide
-
0.1 mM, 66% inhibition, 1 mM, 94% inhibition
P'-geranyl 3,5,7-trihydroxy-3-methylheptanate 7-diphosphate
-
-
P'-geranyl 3,5,8-trihydroxy-3-methyloctanate 8-diphosphate
-
-
P'-geranyl 3,5,9-trihydroxy-3-methylnonanate 9-diphosphate
-
-
P'-geranyl octanate 8-diphosphate
-
-
p-chloromercuribenzoate
phytyl diphosphate
prenyl phosphates
-
competitive with ATP
pyridoxal 5'-phosphate
-
-
SH-group directed reagent
-
-
-
ZnSO4
-
0.1 mM, 90% inhibition
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
arsenate
-
hyperbolic activation curve, 13% activation at 25 mM, 87% activation at 500 mM
atorvastatin
-
besides increases in mRNA level of HMG CoA reductase, treatment increases hepatic mRNA levels of both mevalonate kinase and cob(I)alamin adenosyltransferase
ATP4-
-
most effective activator, maximal activation at 8 mM
cysteine
iodoacetamide
-
10 mM, 20% activation
phosphate
testosterone
treatment of meibomian gland stimulates a significant increase in the mRNA levels of mevalonate kinase, phosphomevalonate kinase, mevalonate diphosphate decarboxylase, isopentenyl diphosphate isomerase, geranylgeranyl diphosphate synthase, squalene epoxidase, lanosterol synthase, lanosterol demethylase, and DELTA7-sterol reductase
UTP
-
stimulation of ATP utilization
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0324 - 2.16
(R)-mevalonate
0.035 - 2.88
(R,S)-mevalonate
0.024 - 0.167
(R,S)mevalonate
0.27
(RS)-mevalonate
-
pH 7.0, 25C
0.019 - 0.27
(RS)mevalonate
0.025 - 7.4
ATP
0.6
Ca-adenosine 5'-O-(2-thio-(R)triphosphate)
-
pH 8.0
0.14
Ca-adenosine 5'-O-(2-thio-(S)triphosphate)
-
pH 8.0
0.22
Cd-adenosine 5'-O-(1-thio-(R)triphosphate)
-
pH 8.0
0.28
Cd-adenosine 5'-O-(1-thio-(S)triphosphate)
-
pH 8.0
0.059
Cd-adenosine 5'-O-(2-thio-(R)triphosphate)
-
pH 8.0
0.46
Cd-adenosine 5'-O-(2-thio-(S)triphosphate)
-
pH 8.0
0.09
Co-adenosine 5'-O-(1-thio-(R)triphosphate)
-
pH 8.0
0.2
Co-adenosine 5'-O-(1-thio-(S)triphosphate)
-
pH 8.0
0.05
Co-adenosine 5'-O-(2-thio-(R)triphosphate)
-
pH 8.0
0.1
Co-adenosine 5'-O-(2-thio-(S)triphosphate)
-
pH 8.0
0.8
CTP
-
pH 10, 37C
0.13 - 5.1
DL-mevalonate
0.3
GTP
-
pH 10, 37C
1.4
ITP
-
pH 10, 37C
0.012 - 9.28
mevalonate
2.44
Mg-adenosine 5'-O-(1-thio-(R)triphosphate)
-
pH 8.0
0.16
Mg-adenosine 5'-O-(1-thio-(S)triphosphate)
-
pH 8.0
0.59
Mg-adenosine 5'-O-(2-thio-(R)triphosphate)
-
pH 8.0
0.12
Mg-adenosine 5'-O-(2-thio-(S)triphosphate)
-
pH 8.0
3.3
Mg2+
-
pH 10, 37C
0.68 - 1.75
MgATP2-
0.29
Mn-adenosine 5'-O-(2-thio-(R)triphosphate)
-
pH 8.0
0.075
Mn-adenosine 5'-O-(2-thio-(S)triphosphate)
-
pH 8.0
0.091
Ni-adenosine 5'-O-(2-thio-(R)triphosphate)
-
pH 8.0
0.14
Ni-adenosine 5'-O-(2-thio-(S)triphosphate)
-
pH 8.0
-
0.041
R,S-mevalonate
-
pH 7.5, 30C
0.0426 - 0.046
RS-mevalonate
1.9
TTP
-
pH 10, 37C
2.8
UTP
-
pH 10, 37C
0.12
Zn-adenosine 5'-O-(2-thio-(R)triphosphate)
-
pH 8.0
0.058
Zn-adenosine 5'-O-(2-thio-(S)triphosphate)
-
pH 8.0
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
3.1 - 28.5
(R)-mevalonate
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.02
3,3-dimethylallyl diphosphate
-
pH 7.0, 25C, recombinant mevalonate kinase
2.7
ADP
-
pH 10, 37C
0.083
dolichol phosphate
-
pH 7.0, 25C, recombinant mevalonate kinase
0.072
Farnesol
-
pH 7.0, 25C, recombinant mevalonate kinase
0.000034 - 0.046
farnesyl diphosphate
0.000029 - 0.045
farnesyl thiodiphosphate
0.002 - 0.116
geranyl diphosphate
0.022 - 0.115
geranylgeranyl diphosphate
0.016
isopentenyl diphosphate
-
pH 7.0, 25C, recombinant mevalonate kinase
0.0036 - 0.016
phytyl diphosphate
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0075
(3R),(5S)-P'-geranyl 3,5,8-trihydroxy-3-methyloctanate 8-diphosphate
Rattus norvegicus
-
pH 7.0, 30C
0.0025
(3S),(5R)-P'-geranyl 3,5,8-trihydroxy-3-methyloctanate 8-diphosphate
Rattus norvegicus
-
pH 7.0, 30C
0.45
8-[[hydroxy(phosphonooxy)phosphoryl]oxy]octanoic acid
Rattus norvegicus
-
pH 7.0, 30C
0.005
geranyl diphosphate
Rattus norvegicus
-
-
0.18
mevalonate 5-diphosphate
Rattus norvegicus
-
-
0.008
P'-geranyl 3,5,7-trihydroxy-3-methylheptanate 7-diphosphate
Rattus norvegicus
-
pH 7.0, 30C
0.0038
P'-geranyl 3,5,8-trihydroxy-3-methyloctanate 8-diphosphate
Rattus norvegicus
-
pH 7.0, 30C
0.0039
P'-geranyl 3,5,9-trihydroxy-3-methylnonanate 9-diphosphate
Rattus norvegicus
-
pH 7.0, 30C
0.0055
P'-geranyl octanate 8-diphosphate
Rattus norvegicus
-
pH 7.0, 30C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.014
-
-
12.4
-
purified enzyme, pH 7.5, 30C
17.5
-
-
24
-
purified enzyme, pH 10, 37C
30.4
-
-
37
-
pH 7.0, 30C
387
-
recombinant mevalonate kinase
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.5 - 7.5
-
-
7.8 - 8
-
-
8.9
-
broad optimum between pH 7.0 and pH 10.0
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5 - 10
-
approx. 10% of maximal activity at pH 5.0, approx. 90% of maximal activity at pH 10.0
5 - 7
-
at least 60% of maximal activity between pH 5.0 and 7.0
5 - 9
-
more than 50% of maximal activity at pH 5.0 and pH 9.0
5.5 - 9
-
approx. 30% of maximal activity at pH 5.5, approx. 60% of maximal activity at pH 9
6.5 - 9
-
approx. 40% of maximal activity at pH 6.5, approx. 70% of maximal activity at pH 9.0
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
35 - 37
-
assay at
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
34
-
wild-type, 25% of maximal activity
37 - 90
-
approx. 25% of maximal activity at 40C and 90C, respectively
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4.7 - 4.8
-
isoelectric focusing
6.2
-
isoelectric focusing
7.8
-
MonoP chromatography
8.4
-
calculated from amino acid sequence
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
-
Manually annotated by BRENDA team
-
enzyme activity during different stages of plant regeneration from nodular callus cultures in white pine, enzyme activity peaked in adventitious shoot organogenesis and at the onset of root formation, overview
Manually annotated by BRENDA team
-
primary skin fibrobasts from healthy donors and patients with Zellweger syndrome
Manually annotated by BRENDA team
-
cell line PLC/PRF/5
Manually annotated by BRENDA team
-
a clonal osteoblast-like mouse calvarial cell line
Manually annotated by BRENDA team
from castrated mice. Treatment with androgens may promote cholesterol biosynthesis
Manually annotated by BRENDA team
-
LPS-stimulated peripheral blood mononuclear cell
Manually annotated by BRENDA team
-
superovulated
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
mevalonate kinase is predominantly localized in peroxisomes, but is easily solubilized and released into the cytosol
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
UNIPROT
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)
Methanosarcina mazei (strain ATCC BAA-159 / DSM 3647 / Goe1 / Go1 / JCM 11833 / OCM 88)
Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
32200
-
sedimentation velocity
33840
-
calculated from the deduced amino acid sequence
34500
-
gel filtration
64600
gel filtration
68000
-
gel filtration
71100
-
sedimentation velocity, 10% of total enzyme
83000
-
stokes radius and partial specific volume
84000
-
recombinant mevalonate kinase, gel filtration
86000
-
gel filtration
94800 - 100000
-
gel filtration, sucrose density gradient
96600 - 100000
-
gel filtration, sucrose density gradient
96600 - 103500
-
gel filtration, sucrose density gradient
97000 - 104000
-
gel filtration
98000 - 102000
-
gel filtration, sucrose density gradient
98000
-
gel filtration
99400 - 101600
-
gel filtration, sucrose density gradient centrifugation
99800 - 103500
-
gel filtration, sucrose density gradient
101900
-
additional bands at 19100, 23500, 45100, 73500 and 271200 Da, native PAGE
104000
-
gel filtration
104600
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
homodimer
monomer
additional information
-
enzyme is involved in post-transcriptional regulation of luteinizing hormone receptor
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
free enzyme, 2.5 A resolution. Modeling of complex with farnesyl thiophosphate
free enzyme and in complex with mevalonate, 1.75 A and 1.9 A resolution, respectively. The mevalonate binds in a deep cavity lined by highly conserved residues. His25 is key for binding and for discrimination of (R)- over (S)-mevalonate, with the main chain amide interacting with the C3 hydroxyl group of (R)-mevalonate, and the side chain contributing, together with Val202 and Thr283, to the construction of a hydrophobic binding site for the C3 methyl substituent. The C5 hydroxyl, where phosphorylation occurs, points towards catalytic residues, Lys18 and Asp155
-
purified recombinant wild-type and selenomethionine-labeled enzyme as apoenzyme and in complex with (R)-mevalonate, hanging drop vapor diffusion method, 0.002 ml of 7.5 mg/ml protein in 10 mM Tris-HCl, pH 8.5, 20 mM NaCl, and 1 mM DTT, in presence of 3-25 mM adenosine 5'-(beta,gamma-imino)triphosphate, 6-50 mM (R)-mevalonate, 10 mM Mg2+, mixing with reservoir solution containing 1.15 M sodium citrate, pH 6.2, 18C, X-ray diffraction structure determination and analysis at 1.75-1.9 A resolution, single-wavelength anomalous dispersion, molecular replacement fails
hanging drop vapor diffusion method, the crystal structure is determined at 2.4 A
hanging drop vapor diffusion method, using 0.32 M MgCl2, 0.08 M bis-Tris pH 5.5, 16% (w/v) PEG 3350, at 18C
complex with farnesyl thiodiphosphate, 2.5 A resolution. Significant farnesyl thiodiphosphate hydrolysis occurs under crystallization conditions, this results in detection of farnesyl thiophosphate in the structure of the binary complex. Binding sites for these metabolites overlap, with the phosphate of farnesyl thiophosphate nearly superimposed on ATP's phosphate and farnesyl thiophosphate's polyisoprenoid chain overlapping ATPs adenosine moiety
-
crystals of mevalonate kinase-MgATP complex are grown at 4C using the sitting drop method by mixing equal volumes of an enzyme solution containing 13 mg/ml protein, 1 mM ATP and 2 mM MgCl2 and a precipitant solution containing 100 mM HEPES buffer, pH 7.5 and 17.5% polyethylene glycol 5000 monomethylester, crystals appear after 3 days, crystal structure at 2.4 A resolution
-
in complex with diphosphomevalonate and Mg2+, diffraction to 2.5 A resolution. Diphosphomevalonate functions as a partial bisubstrate analogue and elicits a ternary-complex like form of the enzyme; purified enzyme in complex with 5-diphosphomevalonate and Mg2+ bound to the active cleft, sitting drop vapour diffusion method, 0.002 ml of 6,0 mg/ml protein in 50 mM HEPES, pH 7.5, 50 mM KCl, 1 mM DTT, 10 mM adenosine 5'-(beta,gamma-imino)triphosphate, 12 mM MgCl2, and 0.5 mM diphosphomevalonate is mixed with 0.002 ml of precipitatnt solution containing 40% v/v PEG 400, and 200 mM sodium formate, at room temperature, X-ray diffraction structure determination and anaylsis at 2.5 A resolution, single-wavelength anomalous diffraction method
-
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4.5 - 9
-
1 h, no loss of activity
641443
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
approx. 50% and 70% loss of activity after 40 min and 90 min, respectively, H20P/V377I double mutant is only slightly more temperature sensitive
44
-
10 min, residual activity of wild-type 50%, of mutant A141C 85%
47
-
10 min, residual activity of wild-type 15%, of mutant A141C 55%
70
-
no loss of activity after 24 h
80
-
1 h, 60% loss of activity
83
-
10 min, residual activity of wild-type 50%, mutants C107S and C281S 20%, mutant C107S/C281S 15%, mutants C107A and C281A 20%, mutant C107A/C281A 18%
90
-
50% loss of activity after 15 min
100
-
50% loss of activity after 5 min
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
almost complete loss of activity after dialysis against 1000 volumes of water, 2-mercaptoethanol, EDTA or glutathione
-
freezing of pure enzyme causes irreversible loss of activity
-
sensitive to dialysis
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-10C, several months, no loss of activity
-
-20C, 50% loss of activity after 1 month
-
4C, 20 mM potassium phosphate, pH 7.5, 5% glycerol, 5 mM 2-mercaptoethanol, 1 month, no loss of activity
-
4C, 5% glycerol, 5 mM 2-mercaptoethanol, stable for more than 1 month
-
5C, stable for several months in buffer containing dithiothreitol
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ammonium sulfate, Blue-Sepharose, ammonium sulfate, Sephadex G-150, ATP-agarose
-
ammonium sulfate, Blue-Sepharose, DEAE-Trisacryl, ATP-agarose, Sephadex G-150
-
ammonium sulfate, calcium phosphate gel, DEAE-cellulose, Sephadex G-200, DEAE-cellulose, Sephadex G-150
-
ammonium sulfate, protamine sulfate, ammonium sulfate, DEAE-cellulose
-
ammonium sulfate, Sephadex G-100
-
ammonium sulfate, Sephadex G-100, DEAE-Sephadex
-
enzyme from cotyledons and leaves, ammonium sulfate, Sephadex G-200, DEAE-Sephadex
-
HiTrap IMAC column chromatography and HiTrap Q column chromatography
-
Ni-NTA bead column chromatography, Resource 15Q column chromatography, and Superdex 200 gel filtration
precipitation at pH 4.5, Sephadex G-200, DEAE-Sephadex
-
protamine sulfate, ammonium sulfate, acid treatment at pH 5.0, ammonium sulfate
-
protamine sulfate, ammonium sulfate, Sephadex G-100
-
Q-Sepharose, Phenyl-Sepharose, Mono Q, Shodex KW 803
-
recombinant dual-tagged His6-GST enzyme from Escherichia coli by affinity chromatography
recombinant enzyme
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography, dialysis, and anion exchange chromatography to homogeneity
recombinant His-tagged mevalonate kinase, hiTrap column
-
recombinant mevalonat kinase-glutathione S-transferase fusion protein, glutathione Sepharose beads
-
recombinant mevalonate kinase, 70C heat treatment, Talon metal-affinity resin
-
recombinant mevalonate kinase, Fast Q, Phenyl-agarose
-
recombinant protein using His-tag
-
recombinant proteins using His-tag
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cloning of ERG12 gene
-
DNA and amino acid sequence determination and anaylsis, overexpression in a procyclic form of Trypanosoma brucei, and expression of His-tagged wild-type enzyme in Escherichia coli strain BL21(DE3), and of His-tagged selenomethionine-labeled enzyme in Escherichia coli strain B834
DNA and amino acid sequence determination and anaylsis, overexprssion in a procyclic form of Trypanosoma brucei
-
expressed as His-tag fusion protein in Escherichia coli BL21(DE3)
-
expressed in Escherichia coli BL21 Star (lambdaDE3) cells
-
expressed in Escherichia coli BL21(DE3)
-
expressed in Escherichia coli BL21(DE3) cells
expressed in HEK293 Flp-In and CV1 Flp-In cells
-
expression in 293T cell
-
expression in Escherichia coli
expression in Trypanosoma brucei
-
expression of His-tagged mevalonate kinase in Escherichia coli
-
expression of wild-type and N301T mutant mevalonate kinase in COS-7 cells
gene MVK, location on chromosome 12q24
-
native and mutant enzymes expressed as His-tag fusion proteins in Escherichia coli BL21(DE3)
-
overexpression in Escherichia coli
-
overexpression in Escherichia coli as dual-tagged His6-GST fusion protein
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
parathyroid hormone, from human source comprising residues 1-34, suppresses the mevalonate kinase in osteoblastic cells
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
A148T
mutation may be responsible for the hyperimmunoglobulinemia phenotype
D204A
-
stable, with 40000fold diminution in kcat. Mutant is able to bind a spin-labeled ATP analogue with stoichiometries and equilibrium binding constants comparable to wild-type
D204N
-
stable, with 40000fold diminution in kcat. Mutant is able to bind a spin-labeled ATP analogue with stoichiometries and equilibrium binding constants comparable to wild-type
E148Q
-
mutation detected in patient with hyperimmunoglobulinemia D and periodic fever syndrome
E193A
-
labile
E193Q
-
50fold diminution in Vmax and 20fold increase Km values for ATP, 40fold increase in Km for mevalonate
E19A
-
destabilization
E19D
-
stable, decrease in Vmax to 40% of wild-type
E19Q
-
destabilization
E296Q
-
stable. Kinetic parameters similar to wild-type
G336S
-
homozygous mutation determined in a patient with severe deficiency in mevalonate kinase associated with nephritis. Catalytic activity is less than 1% of wild-type activity
H20A
-
insoluble upon expression in Escherichia coli
H20P
markedly decreased mevalonate kinase activity when expressed in Escherichia coli
I196A
modest changes in Km and Ki values
I56A
4.5fold increase in Km value for ATP
L264F
markedly decreased mevalonate kinase activity when expressed in Escherichia coli
L265P
markedly decreased mevalonate kinase activity when expressed in Escherichia coli
L53A
modest changes in Km and Ki values
N301T
5-20% of wild-type activity
P165L
mutation may be responsible for the hyperimmunoglobulinemia phenotype
Q390P
-
mutation determined in patient with mevalonate kinase deficiency. Gene additionally has a four-base deletion c.475-478 delACTG
R388X
modest changes in Km and Ki values
S145A
-
37% of wild-type activity
S146A
-
0.02% of wild-type activity
S201A
-
200% of wild-type activity
S378P/V377I/R92Q
-
naturally occuring mutation in the MVK gene, the mutation leads to reduced enzyme activity, which participates in the development of the hyperimmunoglobulinemia D and periodic fever syndrome, HIDS, an autosomal recessively inherited autoinflammatory disease, R92Q is a low-penetrance mutation, phenotype, overview
T104A
modest changes in Km and Ki values
T104A/I196A
39fold increase in Ki value
T104A/I196A/R388X
11fold increase in Km value for mevalonate
T243A
-
39% of wild-type activity
T243I
markedly decreased mevalonate kinase activity when expressed in Escherichia coli
V310M
markedly decreased mevalonate kinase activity when expressed in Escherichia coli
V377I
mutation may be responsible for the hyperimmunoglobulinemia phenotype
V377I/I268T
-
mutation determined in patients with hyperimmunoglobulinemia D and periodic fever syndrome. Patients developed significant B cell cytopenia with hypogammaglobulinemia. Therapy of prednisone, azathioprine, and intravenous immunoglobulins resulted in reduced incidence and severity of febrile attacks
V377I/R92Q
-
naturally occuring mutation in the MVK gene, the mutation leads to reduced enzyme activity, which participates in the development of the hyperimmunoglobulinemia D and periodic fever syndrome, HIDS, an autosomal recessively inherited autoinflammatory disease, R92Q is a low-penetrance mutation, phenotype, overview
Y149A
8fold increase in Km value for mevalonate
C107A
-
decrease in temperature stability, slight increase in Km value for ATP
C107S
-
decrease in temperature stability, slight increase in Km value for ATP
C107S/C281S
-
decrease in temperature stability, slight increase in Km value for ATP
C197A/C281A
-
decrease in temperature stability, slight increase in Km value for ATP
C281A
-
decrease in temperature stability, slight increase in Km value for ATP
C281S
-
decrease in temperature stability, slight increase in Km value for ATP
K272A
-
18% of wild-type activity
K272R
-
18% of wild-type activity
R196L
-
5% of wild-type activity
R196V
-
60% of wild-type activity
A141C
-
significantly higher thermal activity than wild-type
D204N
-
mutation in active site, decrease in luteinizing hormone receptor mRNA binding
D316A
-
mutation outside tie active site, no change in luteinizing hormone receptor mRNA binding
E193Q
-
mutation in active site, decrease in luteinizing hormone receptor mRNA binding
E193Q/D204N
-
significant decrease in luteinizing hormone receptor mRNA binding
E193Q/K13A
-
significant decrease in luteinizing hormone receptor mRNA binding
H20K
-
expressed in inclusion bodies that can be solubilized in 8 M urea, refolding to a soluble protein was unsuccessful indicating irreversible structural changes
H20L
-
no significant changes in secondary structure, increased Km for both substrates
H20Y
-
no significant changes in secondary structure, increased Km for both substrates
I196A
-
modest changes in Km and Ki values
I56A
-
4.5fold increase in Km value for ATP
K13A
-
mutation in active site, decrease in luteinizing hormone receptor mRNA binding
K13M
-
56fold decrease in activity
L53A
-
modest changes in Km and Ki values
R388X
-
modest changes in Km and Ki values
S146A
-
mutation in active site, decrease in luteinizing hormone receptor mRNA binding
S146A/E193Q
-
significant decrease in luteinizing hormone receptor mRNA binding
S314A
-
mutation outside the active site, no change in luteinizing hormone receptor mRNA binding
T104A
-
modest changes in Km and Ki values
T104A/I196A
-
39fold increase in Ki value
T104A/I196A/R388X
-
11fold increase in Km value for mevalonate
Y149A
-
8fold increase in Km value for mevalonate
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
diagnostics
-
mutations in the mevalonate kinase gene cause the hyperimmunoglobulin D syndrome, HIDS, and are an appropriate marker for the disease
medicine
synthesis
-
production of amorpha-4,11-diene by an engineered strain of Escherichia coli containing codon-optimized MevT and amorphadiene synthase operons, and additional copies of mevalonate kinase and amorphadiene synthase genes, which could be identified as rate-limiting enzymes
Show AA Sequence (907 entries)
Please use the Sequence Search for a certain query.