Information on EC 2.7.1.36 - mevalonate kinase

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

EC NUMBER
COMMENTARY
2.7.1.36
-
RECOMMENDED NAME
GeneOntology No.
mevalonate kinase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
ATP + (R)-mevalonate = ADP + (R)-5-phosphomevalonate
show the reaction diagram
sequential mechanism
-
ATP + (R)-mevalonate = ADP + (R)-5-phosphomevalonate
show the reaction diagram
sequential mechanism
-
ATP + (R)-mevalonate = ADP + (R)-5-phosphomevalonate
show the reaction diagram
catalytic reaction mechanism, substrate binding structure involves key residue His25 in a deep cavity lined by highly conserved residues, Lys18, Asp155, Val202, and Thr283 are involved in catalysis
Q4Q6K7
ATP + (R)-mevalonate = ADP + (R)-5-phosphomevalonate
show the reaction diagram
role for residue E193 in interacting with the cation of the MgATP substrate, and for D204 as the catalytic base that facilitates deprotonation of the C5 hydroxyl of mevalonic acid
-
ATP + (R)-mevalonate = ADP + (R)-5-phosphomevalonate
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
phospho group transfer
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
Biosynthesis of secondary metabolites
-
isoprene biosynthesis II (engineered)
-
Metabolic pathways
-
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.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
ATP:mevalonate 5-phosphotransferase
-
-
-
-
kinase, mevalonate (phosphorylating)
-
-
-
-
mevalonate 5-phosphotransferase
-
-
-
-
mevalonate phosphokinase
-
-
-
-
mevalonic acid kinase
-
-
-
-
mevalonic kinase
-
-
-
-
MVA kinase
-
-
-
-
SSO0383
Q980D2
gene name
SSO0383
Q980D2
gene name
-
CAS REGISTRY NUMBER
COMMENTARY
9026-52-2
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
(L.) G. Don
-
-
Manually annotated by BRENDA team
Citrus sp.
orange
-
-
Manually annotated by BRENDA team
pumpkin
-
-
Manually annotated by BRENDA team
rubber tree
-
-
Manually annotated by BRENDA team
enhanced and inappropriate expression of mevalonate kinase may lead to increased metabolism of mevalonate and phosphorylation of hitherto unknown cellular proteins
-
-
Manually annotated by BRENDA team
french population
-
-
Manually annotated by BRENDA team
mevalonate kinase deficiency causes mevalonic aciduria, hyperimmunoglobuinemia D and periodic fever syndrome
UniProt
Manually annotated by BRENDA team
patient wih mevalonate kinase deficiency
-
-
Manually annotated by BRENDA team
patient with hyperimmunoglobulinemia D and periodic fever syndrome
-
-
Manually annotated by BRENDA team
patient with mevalonate kinase deficiency
-
-
Manually annotated by BRENDA team
patients with Behcets disease
-
-
Manually annotated by BRENDA team
patients with hyperimmunoglobulinemia D and periodic fever syndrome
-
-
Manually annotated by BRENDA team
patients with mevalonic aciduria
-
-
Manually annotated by BRENDA team
Kalanchoe crenata
-
-
-
Manually annotated by BRENDA team
murine model of hyper-IgD syndrome
-
-
Manually annotated by BRENDA team
french bean
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
-
mutations in the mevalonate kinase gene cause the hyperimmunoglobulin D syndrome, HIDS, an autosomal recessive autoinflammatory disease
metabolism
Q8DR51
the enzyme is regulating the mevalonate pathway in Streptococcus pneumoniae, it is strongly feedback-inhibited by diphosphomevalonate, the penultimate compound in the pathway, overview
metabolism
-
the enzyme is part of the mevalonate pathway leading to the production of farnesyl diphosphate and geranylgeranyl diphosphate, overview
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 ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
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
-
-
-
-
?
ADP + mevalonate
?
show the reaction diagram
-
-
-
-
?
ATP + (R)-mevalonate
ADP + (R)-5-phosphomevalonate
show the reaction diagram
-
-
-
-
?
ATP + (R)-mevalonate
ADP + (R)-5-phosphomevalonate
show the reaction diagram
-
-
-
-
?
ATP + (R)-mevalonate
ADP + (R)-5-phosphomevalonate
show the reaction diagram
-
-
-
-
?
ATP + (R)-mevalonate
ADP + (R)-5-phosphomevalonate
show the reaction diagram
-
-
-
-
?
ATP + (R)-mevalonate
ADP + (R)-5-phosphomevalonate
show the reaction diagram
-
-
-
?
ATP + (R)-mevalonate
ADP + (R)-5-phosphomevalonate
show the reaction diagram
-
-
-
-
r
ATP + (R)-mevalonate
ADP + (R)-5-phosphomevalonate
show the reaction diagram
-
-
-
-
?
ATP + (R)-mevalonate
ADP + (R)-5-phosphomevalonate
show the reaction diagram
-
-
-
-
?
ATP + (R)-mevalonate
ADP + (R)-5-phosphomevalonate
show the reaction diagram
-
-
-
-
?
ATP + (R)-mevalonate
ADP + (R)-5-phosphomevalonate
show the reaction diagram
-, Q4Q6K7
-
-
-
r
ATP + (R)-mevalonate
ADP + (R)-5-phosphomevalonate
show the reaction diagram
Q03426
-
-
-
?
ATP + (R)-mevalonate
ADP + (R)-5-phosphomevalonate
show the reaction diagram
-
-
-
-
?
ATP + (R)-mevalonate
ADP + (R)-5-phosphomevalonate
show the reaction diagram
Q8DR51
-
-
-
?
ATP + (R)-mevalonate
ADP + (R)-5-phosphomevalonate
show the reaction diagram
-, Q8PW39
-
-
-
?
ATP + (R)-mevalonate
ADP + (R)-5-phosphomevalonate
show the reaction diagram
-
involved in cholesterol synthesis
-
-
?
ATP + (R)-mevalonate
ADP + (R)-5-phosphomevalonate
show the reaction diagram
-
involved in cholesterol synthesis
-
-
?
ATP + (R)-mevalonate
ADP + (R)-5-phosphomevalonate
show the reaction diagram
-
involved in cholesterol synthesis, decreased enzyme activity involved in mevalonic aciduria and hyperimmunoglobulin D syndrome
-
-
?
ATP + (R)-mevalonate
ADP + (R)-5-phosphomevalonate
show the reaction diagram
-
involved in cholesterol, steroid hormones und terpenoids synthesis
-
-
?
ATP + (R)-mevalonate
ADP + (R)-5-phosphomevalonate
show the reaction diagram
-
involved in isopentenyl diphosphate synthesis
-
-
?
ATP + (R)-mevalonate
ADP + (R)-5-phosphomevalonate
show the reaction diagram
-
involved in isopentenyl diphosphate synthesis
-
-
?
ATP + (R)-mevalonate
ADP + (R)-5-phosphomevalonate
show the reaction diagram
-
a step in the mevalonate pathway, overview
-
-
?
ATP + (R)-mevalonate
ADP + (R)-5-phosphomevalonate
show the reaction diagram
-
the enzyme catalyzes a step in the isoprenoid biosynthetic pathway via the essential intermediate 5-diphosphomevalonate, substrate binding structure, overview
-
-
?
ATP + (R)-mevalonate
ADP + (R)-5-phosphomevalonate
show the reaction diagram
-
a step in the production of farnesyldiphosphate and geranylgeranyl diphosphate, overview
-
-
?
ATP + (R)-mevalonate
ADP + (R)-5-phosphomevalonate
show the reaction diagram
Q980D2
the enzyme is involved in the modified mevalonate pathway. The recombinant protein is active. However in vitro conversion of the intermediates in the classical and modified pathways by cell-free extract from Sulfolobus solfataricus indicates that only the classical pathway likely works in the organism
-
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
-
-
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
-
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
-
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
-
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
-
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
-
-
-
-
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
-
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
-
-
-
-
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
-
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
-
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
-
-
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
-
-
-
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
P17256
-
-
-
-
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
-
-
-
-
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
-
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
-
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
-
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
-
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
-
-
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
-
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
-
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
-
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
-
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
-
-
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
-
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
-
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
-
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
-
-
-
-
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
-
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
-
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
-
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
-
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
-
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
-
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
-
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
-
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
-
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
-
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
-
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
-
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
-
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
-
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
Kalanchoe crenata
-
-
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
no activity with GTP
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
no activity with GTP
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
stereospecific reaction with R-mevalonate
-
-
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
ATP is the most effective phosphate donor
-
-
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
ATP is the most effective phosphate donor
-
ir
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
ATP is the most effective phosphate donor
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
ATP is the most effective phosphate donor
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
no activity with CTP
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
no activity with ADP, GTP and UTP
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
no activity with ITP, UTP and ADP
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
no activity with ADP
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
no activity with ADP
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
ATPgammaS, ATPalphaS and ATPbetaS can act as substrates in presence of different activating divalent metal cations, in the presence of Mg2+ the R diastereomers of both ATPalphaS and ATPbetaS are the preferred substrates, in presence of Cd2+ the S diastereomers are more active
-
-
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
mevalonate kinase is probably involved in regulation of cholesterol biosynthesis
-
-
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
involved in mevalonate pathway of terpenoid biosynthesis
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
via mevalonate pathway involved in isoprenoid biosynthesis
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
part of the cholesterol and nonsterol isoprene biosynthetic pathway
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
enzyme may play a key role in regulating cholesterol biosynthesis
-
?
CTP + (R)-mevalonate
CDP + (R)-5-phosphomevalonate
show the reaction diagram
-
-
-
-
?
CTP + mevalonate
CDP + phosphomevalonate
show the reaction diagram
-
-
-
?
CTP + mevalonate
CDP + phosphomevalonate
show the reaction diagram
-
weak activity
-
?
CTP + mevalonate
CDP + phosphomevalonate
show the reaction diagram
-
18% of activity with ATP
-
?
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
-
-
-
?
GTP + mevalonate
GDP + phosphomevalonate
show the reaction diagram
-
-
-
?
GTP + mevalonate
GDP + phosphomevalonate
show the reaction diagram
-
weak activity
-
?
GTP + mevalonate
GDP + phosphomevalonate
show the reaction diagram
-
18% of the activity with ATP
-
?
ITP + (R)-mevalonate
IDP + (R)-5-phosphomevalonate
show the reaction diagram
-
-
-
-
?
ITP + mevalonate
IDP + phosphomevalonate
show the reaction diagram
-
-
-
?
ITP + mevalonate
IDP + phosphomevalonate
show the reaction diagram
-
-
-
?
ITP + mevalonate
IDP + phosphomevalonate
show the reaction diagram
-
-
-
?
ITP + mevalonate
IDP + phosphomevalonate
show the reaction diagram
-
as effective as ATP
-
?
ITP + mevalonate
IDP + phosphomevalonate
show the reaction diagram
-
88% of activity with ATP
-
?
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
-
-
-
?
UTP + mevalonate
UDP + phosphomevalonate
show the reaction diagram
-
-
-
?
UTP + mevalonate
UDP + phosphomevalonate
show the reaction diagram
-
-
-
?
UTP + mevalonate
UDP + phosphomevalonate
show the reaction diagram
-
weak activity
-
?
UTP + mevalonate
UDP + phosphomevalonate
show the reaction diagram
-
61% of the activity with ATP
-
?
XTP + mevalonate
XDP + phosphomevalonate
show the reaction diagram
-
27% of the activity with ATP
-
?
ITP + mevalonate
IDP + phosphomevalonate
show the reaction diagram
-
36% of activity with ATP
-
?
additional information
?
-
-
the enzyme catalyzes a step in the isoprenoid biosynthetic pathway, which leads to a huge number of compounds that play important roles in plant growth and development
-
-
-
additional information
?
-
-
mevalonate kinase is directly involved in regulation of luteinizing hormone receptor expression
-
-
-
additional information
?
-
Q8DR51
the recombinant enzyme phosphorylates racemic vinyl, ethyl, n-propyl, n-butyl, i-butyl, 2-propenyl, allyl, ethynyl, and 1-propynyl mevalonate lactone analogues, that are diphosphorylated by phosphomevalonate kinase, EC 2.7.4.2, in a second step, overview
-
-
-
additional information
?
-
Q980D2
the enzyme is involved in the modified mevalonate pathway. The recombinant protein is active. However in vitro conversion of the intermediates in the classical and modified pathways by cell-free extract from Sulfolobus solfataricus indicates that only the classical pathway likely works in the organism
-
-
-
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 + (R)-mevalonate
ADP + (R)-5-phosphomevalonate
show the reaction diagram
-
-
-
-
?
ATP + (R)-mevalonate
ADP + (R)-5-phosphomevalonate
show the reaction diagram
-
-
-
-
r
ATP + (R)-mevalonate
ADP + (R)-5-phosphomevalonate
show the reaction diagram
Q4Q6K7
-
-
-
r
ATP + (R)-mevalonate
ADP + (R)-5-phosphomevalonate
show the reaction diagram
Q8DR51
-
-
-
?
ATP + (R)-mevalonate
ADP + (R)-5-phosphomevalonate
show the reaction diagram
-
involved in cholesterol synthesis
-
-
?
ATP + (R)-mevalonate
ADP + (R)-5-phosphomevalonate
show the reaction diagram
-
involved in cholesterol synthesis
-
-
?
ATP + (R)-mevalonate
ADP + (R)-5-phosphomevalonate
show the reaction diagram
-
involved in cholesterol synthesis, decreased enzyme activity involved in mevalonic aciduria and hyperimmunoglobulin D syndrome
-
-
?
ATP + (R)-mevalonate
ADP + (R)-5-phosphomevalonate
show the reaction diagram
-
involved in cholesterol, steroid hormones und terpenoids synthesis
-
-
?
ATP + (R)-mevalonate
ADP + (R)-5-phosphomevalonate
show the reaction diagram
-
involved in isopentenyl diphosphate synthesis
-
-
?
ATP + (R)-mevalonate
ADP + (R)-5-phosphomevalonate
show the reaction diagram
-
involved in isopentenyl diphosphate synthesis
-
-
?
ATP + (R)-mevalonate
ADP + (R)-5-phosphomevalonate
show the reaction diagram
-
a step in the mevalonate pathway, overview
-
-
?
ATP + (R)-mevalonate
ADP + (R)-5-phosphomevalonate
show the reaction diagram
-
the enzyme catalyzes a step in the isoprenoid biosynthetic pathway via the essential intermediate 5-diphosphomevalonate
-
-
?
ATP + (R)-mevalonate
ADP + (R)-5-phosphomevalonate
show the reaction diagram
-
a step in the production of farnesyldiphosphate and geranylgeranyl diphosphate, overview
-
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
mevalonate kinase is probably involved in regulation of cholesterol biosynthesis
-
-
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
involved in mevalonate pathway of terpenoid biosynthesis
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
via mevalonate pathway involved in isoprenoid biosynthesis
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
part of the cholesterol and nonsterol isoprene biosynthetic pathway
-
?
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
-
enzyme may play a key role in regulating cholesterol biosynthesis
-
?
additional information
?
-
-
the enzyme catalyzes a step in the isoprenoid biosynthetic pathway, which leads to a huge number of compounds that play important roles in plant growth and development
-
-
-
additional information
?
-
-
mevalonate kinase is directly involved in regulation of luteinizing hormone receptor expression
-
-
-
additional information
?
-
Q980D2
the enzyme is involved in the modified mevalonate pathway. The recombinant protein is active. However in vitro conversion of the intermediates in the classical and modified pathways by cell-free extract from Sulfolobus solfataricus indicates that only the classical pathway likely works in the organism
-
-
-
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
ATP
Q4Q6K7
helix alpha2 and the preceding polypeptide adopt a conformation impeding access to the nucleotide triphosphate binding site suggesting that a conformational rearrangement is required to allow ATP binding, the ATP binding structure is distinct from related enzymes, overview
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Ba2+
-
can partially replace Mg2+ in activation
Ba2+
-
at 5 mM 10% of activity with Mg2+; can partially replace Mg2+ in activation
Ba2+
-
weak stimulation
Ca2+
-
at 5 mM 10% of the activity with Mn2+; can partially replace Mn2+ in activation
Ca2+
-
can partially replace Mn2+ in activation
Ca2+
-
71% of activity with Mg2+; can partially replace Mn2+ in activation
Ca2+
-
can partially replace Mn2+ in activation
Ca2+
-
can replace for Mg2+
Co2+
-
approx. 15% of the activity with Mn2+ at 5 mM; can partially replace Mn2+ in activation
Co2+
-
can partially replace Mn2+ in activation; weak stimulation
Co2+
-
approx. 18% of activity with Mg2+ or Mn2+ at 2 mM
Fe2+
-
at 5 mM about 10% of the activity with Mn2+; can partially replace Mn2+ in activation
Fe2+
-
weak stimulation
Fe2+
-
approx. 30% of activity with Mg2+ or Mn2+ at 2 mM
Mg2+
-
Mg2+ becomes increasingly active at higher concentrations and at sufficiently high concentrations the most active metal ion
Mg2+
-
activates; Mn2+ or Mg2+ required; most active divalent cation
Mg2+
-
presence of free ATP4- results in a biphasic Lineweaver-Burk plot with 2 apparent Km-values for MgATP2-: 0.14 mM and 0.006 mM
Mg2+
-
maximal activity at 9 mM
Mg2+
-
maximal activity at 6-8 mM
Mg2+
-
maximal activity at 4 mM; maximal activity at 4 mM, 77% of activity with Mn2+
Mg2+
-
required
Mg2+
-
required
Mg2+
Q4Q6K7
-
Mg2+
-
-
Mg2+
-
binding structure, overview
Mn2+
-
divalent cation required for activity; higher activation than with Mg2+ at concentrations below approx. 0.008 mM, lower activation than with Mg2+ above
Mn2+
-
divalent cation required for activity; maximal activation at approx. 0.0013 mM
Mn2+
-
most active at low concentrations
Mn2+
-
can partially replace Mg2+ in activation, maximal activation at 2.5 mM, inhibition above; most active at low concentrations
Mn2+
-
maximal activation at 2 mM; most active at low concentrations
Mn2+
-
maximal acitvation at 2 mM, inhibition above
Mn2+
-
divalent cation required for activity; maximal activation at 1 mM; most active at low concentrations
Mn2+
-
as effectiv as Mg2+; divalent cation required for activity
Mn2+
-
25% of the activity with Mg2+
Mn2+
-
can replace for Mg2+
Sr2+
-
can partially replace Mg2+ in activation, 8% of activity with Mg2+ at 5 mM
Zn2+
-
at 5 mM about 30% of the activity of Mn2+; can partially replace Mn2+ in activation
Zn2+
-
approx. 35% of activity with Mg2+ or Mn2+ at 2 mM
Zn2+
-
can replace for Mg2+
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
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
-
-
ADP
-
very weak inhibition
ADP
-
product inhibition vs. ATP at concentration above 2 mM
CuSO4
-
10 mM, almost complete inhibition
CuSO4
-
0.1 mM, 56% inhibition, 1 mM, 77% inhibition
diphosphomevalonate
-
functions as a partial bisubstrate analogue and elicits a ternary-complex like form of the enzyme
diphosphomevalonate
Q8DR51
strong feedback inhibitor of the enzyme
dolichol phosphate
-
-
EDTA
-
10 mM, almost complete inhibition
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
farnesyl diphosphate
-
potent inhibitor
farnesyl diphosphate
-
-
farnesyl diphosphate
-
-
farnesyl diphosphate
-
0.3 mM, approx. 75% inhibition
farnesyl diphosphate
-
-
farnesyl diphosphate
-
0.01 mM, 65% inhibition
farnesyl diphosphate
-
competitive vs. ATP
farnesyl diphosphate
-
-
farnesyl diphosphate
-
-
farnesyl diphosphate
-
feedback inhibition, competitive with ATP
farnesyl diphosphate
-
competitive with ATP
farnesyl diphosphate
Q03426
feedback regulation
farnesyl thiodiphosphate
-
feedback inhibition, competitive with ATP
farnesyl thiodiphosphate
-
competitive with ATP, feedback regulation
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
-
potent inhibitor
geranyl diphosphate
-
-
geranyl diphosphate
-
-
geranyl diphosphate
-
0.3 mM, approx. 10% inhibition
geranyl diphosphate
-
0.01 mM, 55% inhibition
geranyl diphosphate
-
-
geranyl diphosphate
-
-
geranyl diphosphate
-
competitive with ATP
geranyl diphosphate
-
-
geranylgeranyl diphosphate
-
0.3 mM, approx. 90% inhibition
geranylgeranyl diphosphate
-
-
geranylgeranyl diphosphate
-
competitive with ATP
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
-
at high concentrations
mevalonate
-
substrate inhibition at millimolar concentrations, 50% inhibition at 2.88 mM
mevalonate 5-diphosphate
-
-
mevalonate 5-phosphate
-
0.3 mM, approx. 45% inhibition
mevalonate 5-phosphate
-
noncompetitive vs. ATP, mixed-type vs. mevalonate
Mn2+
-
inhibition above 2.5 mM
Mn2+
-
inhibition at high concentrations
Mn2+
-
inhibition at high concentrations
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
-
0.1 mM, 83% inhibition, completely reversed by reduced glutathione
p-chloromercuribenzoate
-
activity can be almost completely restored by incubation with an excess of cysteine
p-chloromercuribenzoate
-
1 mM, almost complete inhibition
p-chloromercuribenzoate
-
0.1 mM, 95% inhibition, 1 mM, complete inhibition
phytyl diphosphate
-
0.3 mM, almost complete inhibition
prenyl phosphates
-
competitive with ATP
pyridoxal 5'-phosphate
-
-
SH-group directed reagent
-
-
-
ZnSO4
-
0.1 mM, 90% inhibition
Mn2+
-
inhibition at 10 mM in crude extracts
additional information
-
-
-
additional information
-
not inhibited by isopentenyl and dimethyldiphosphate and phosphate
-
additional information
-
not inhibited by iodoacetamide
-
additional information
-
not inhibited by R-mevalonate 5-diphosphate, geraniol and dolichol up to 0.084, 0.226 and 0.68 mM, respectively
-
additional information
-
no inhibition with AMP
-
additional information
-
organic synthesis of bisubstrate analogues, organic synthesis and biological characterization of bifunctional molecules, which can inhibit both MVK and mevalonate 5-diphosphate decarboxylase
-
additional information
Q8DR51
synthesis of a series of C3-substituted mevalonate analogues to probe the steric and electronic requirements of the mevalonate kinase active site for development of specific mechanism-based inhibitors, overview
-
additional information
-
the enzyme is not inhibited by dimethylallyl diphosphate, geranyl diphosphate, farnesyl diphosphate, isopentenyl monophosphate, and diphosphomevalonate
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
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
-
or to a lesser extent other SH-compounds required
cysteine
-
not required for activity
iodoacetamide
-
10 mM, 20% activation
phosphate
-
required for activity
phosphate
-
50% activation at 100 mM
testosterone
Q9R008
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]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0324
-
(R)-mevalonate
Q03426
mutant T104A, 30C, pH 7.5
0.035
-
(R)-mevalonate
-
native enzyme, pH 7.5, 25C
0.035
-
(R)-mevalonate
-
wild-type, pH 7.5, 34C
0.0408
-
(R)-mevalonate
Q03426
wild-type, 30C, pH 7.5
0.0459
-
(R)-mevalonate
Q03426
mutant R388X, 30C, pH 7.5
0.0473
-
(R)-mevalonate
Q03426
mutant L54A, 30C, pH 7.5
0.061
-
(R)-mevalonate
-
mutant C281S, pH 7.5, 34C
0.068
-
(R)-mevalonate
-
apparent value, in 50 mM Tris, 50 mM NaCl (pH 7.6), at 30C
0.07
-
(R)-mevalonate
-
mutant C107A, pH 7.5, 34C
0.071
-
(R)-mevalonate
-
mutant C107A/C281A, pH 7.5, 34C
0.0745
-
(R)-mevalonate
Q03426
mutant T104A/I196A, 30C, pH 7.5
0.076
-
(R)-mevalonate
-
mutant C107S, pH 7.5, 34C
0.106
-
(R)-mevalonate
-
mutant C281A, pH 7.5, 34C; wild-type, pH 7.5, 34C
0.111
-
(R)-mevalonate
-
mutant C107S/C281S, pH 7.5, 34C
0.1163
-
(R)-mevalonate
Q03426
mutant I196A, 30C, pH 7.5
0.186
-
(R)-mevalonate
-
mutant A141C, pH 7.5, 34C
0.228
-
(R)-mevalonate
Q03426
mutant I56A, 30C, pH 7.5
0.323
-
(R)-mevalonate
Q03426
mutant Y149A, 30C, pH 7.5
0.4591
-
(R)-mevalonate
Q03426
mutant T104A/I196A/R388X, 30C, pH 7.5
0.616
-
(R)-mevalonate
-
H20L mutant enzyme, pH 7.5, 25C
2.16
-
(R)-mevalonate
-
H20Y mutant enzyme, pH 7.5, 25C
0.035
-
(R,S)-mevalonate
-
pH 7.5, 25C, recombinant mevalonate kinase
0.069
-
(R,S)-mevalonate
-
pH 8.0, 70C, recombinant mevalonate kinase
0.15
-
(R,S)-mevalonate
-
pH 7.0, 25C, recombinant mevalonate kinase
0.288
-
(R,S)-mevalonate
-
pH 7.0, 30C
2.88
-
(R,S)-mevalonate
-
pH 7.0, 30C, K13M mutant mevalonate kinase
0.024
-
(R,S)mevalonate
-
-
0.167
-
(R,S)mevalonate
-
V377I mutant mevalonate kinase
0.27
-
(RS)-mevalonate
-
pH 7.0, 25C
0.019
-
(RS)mevalonate
-
liver mevalonate kinase
0.069
-
(RS)mevalonate
-
-
0.069
-
(RS)mevalonate
-
recombinant mevalonate kinase
0.27
-
(RS)mevalonate
-
liver mevalonate kinase
0.025
-
ATP
-
mutant D204A, pH 7.0, 30C
0.0403
-
ATP
Q03426
mutant T104A, 30C, pH 7.5
0.066
-
ATP
-
mutant D204N, pH 7.0, 30C
0.074
-
ATP
-
-
0.074
-
ATP
-
wild-type, pH 7.0, 30C
0.092
-
ATP
-
pH 8.0, 70C, recombinant mevalonate kinase
0.092
-
ATP
-
recombinant mevalonate kinase
0.1
-
ATP
-
V377I mutant mevalonate kinase
0.113
-
ATP
-
mutant E19D, pH 7.0, 30C
0.13
-
ATP
-
pH 7.5, 30C
0.131
-
ATP
-
mutant E296Q, pH 7.0, 30C
0.14
-
ATP
-
pH 7.9, 37C
0.14
-
ATP
-
pH 7.9, 37C
0.15
-
ATP
-
pH 7.5, 30C, recombinant S145A mutant mevalonate kinase
0.166
-
ATP
-
pH 7.0, 30C, K13M mevalonate kinase
0.1784
-
ATP
Q03426
wild-type, 30C, pH 7.5
0.2321
-
ATP
Q03426
mutant L54A, 30C, pH 7.5
0.3
-
ATP
-
liver mevalonate kinase
0.3018
-
ATP
Q03426
mutant I196A, 30C, pH 7.5
0.3077
-
ATP
Q03426
mutant T104A/I196A, 30C, pH 7.5
0.339
-
ATP
-
pH 7.5, 30C
0.38
-
ATP
-
pH 7.5, 30C, recombinant T243A mevalonate kinase
0.3954
-
ATP
Q03426
mutant T104A/I196A/R388X, 30C, pH 7.5
0.41
-
ATP
-
pH 7.5, 30C, recombinant S146A mevalonate kinase
0.44
-
ATP
-
pH 7.0, 25C, recombinant mevalonate kinase
0.464
-
ATP
-
apparent value, in 50 mM Tris, 50 mM NaCl (pH 7.6), at 30C
0.51
-
ATP
-
pH 7.5, 30C, recombinant S201A mevalonate kinase
0.614
-
ATP
Q03426
mutant R388X, 30C, pH 7.5
0.6896
-
ATP
Q03426
mutant Y149A, 30C, pH 7.5
0.69
-
ATP
-
pH 8.0
0.8097
-
ATP
Q03426
mutant I56A, 30C, pH 7.5
0.95
-
ATP
-
pH 7.5, 25C, recombinant mevalonate kinase
0.95
-
ATP
-
wild-type, pH 7.5, 34C
0.953
-
ATP
-
native enzyme, pH 7.5, 25C
0.97
-
ATP
-
mutant A141C, pH 7.5, 34C
1.1
-
ATP
-
pH 10, 37C
1.18
-
ATP
-
pH 7.5, 34C
1.18
-
ATP
-
wild-type, pH 7.5, 34C
1.22
-
ATP
-
pH 7.5, 34C, K272R mutant mevalonate kinase
1.24
-
ATP
-
pH 7.0, 30C
1.5
-
ATP
-
pH 7.0, 30C
1.54
-
ATP
-
pH 7.0, 30C, enzyme from etiolated cotyledons
1.54
-
ATP
-
pH 7.5, 34C, R196L mutant mevalonate kinase
1.56
-
ATP
-
mutant E193Q, pH 7.0, 30C
1.58
-
ATP
-
mutant C107A/C281A, pH 7.5, 34C
1.75
-
ATP
-
pH 7.0, 30C, enzyme fom green leaves
1.75
-
ATP
-
liver mevalonate kinase
1.81
-
ATP
-
H20L mutant enzyme, pH 7.5, 25C
2
-
ATP
-
pH 7.0, 30C
2
-
ATP
-
pH 7.0, 30C
2
-
ATP
-
pH 7.5, 30C
2.61
-
ATP
-
mutant C107A, pH 7.5, 34C
2.7
-
ATP
-
H20Y mutant enzyme enzyme, pH 7.5, 25C
2.76
-
ATP
-
mutant C281A, pH 7.5, 34C
2.95
-
ATP
-
pH 7.5, 34C, K272A mutant mevalonate kinase
2.97
-
ATP
-
mutant C281S, pH 7.5, 34C
2.98
-
ATP
-
pH 7.5, 34C, R196Q mutant mevalonate kinase
3
-
ATP
-
pH 7.5, 34C, R196V mutant mevalonate kinase
3.11
-
ATP
-
mutant C107S, pH 7.5, 34C
3.36
-
ATP
-
mutant C107S/C281S, pH 7.5, 34C
5.4
-
ATP
-
pH 7.0, 30C
7.4
-
ATP
-
pH 7.0, 30C
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
-
DL-mevalonate
-
pH 7.5, 30C
0.62
-
DL-mevalonate
-
-
5.1
-
DL-mevalonate
-
pH 7.0, 35C
0.3
-
GTP
-
pH 10, 37C
1.4
-
ITP
-
pH 10, 37C
0.012
-
mevalonate
-
mutant D204N, pH 7.0, 30C
0.024
-
mevalonate
-
wild-type, pH 7.0, 30C
0.05
-
mevalonate
-
pH 7.9, 37C
0.052
-
mevalonate
-
mutant E19D, pH 7.0, 30C
0.076
-
mevalonate
-
pH 7.5, 30C
0.08
-
mevalonate
-
pH 7.9, 37C
0.11
-
mevalonate
-
pH 7.5, 34C
0.11
-
mevalonate
-
mutant E296Q, pH 7.0, 30C
0.2
-
mevalonate
-
mutant D204A, pH 7.0, 30C
0.25
-
mevalonate
-
pH 7.5, 34C, K272R mutant mevalonate kinase
0.253
-
mevalonate
-
pH 7.5, 30C, recombinant S145A mevalonate kinase
0.33
-
mevalonate
-
pH 10, 37C
0.47
-
mevalonate
-
pH 7.5, 30C, recombinant T243A mevalonate kinase
0.51
-
mevalonate
-
pH 7.5, 30C, recombinant S146A mevalonate kinase
0.51
-
mevalonate
-
pH 7.5, 34C, K272A mutant mevalonate kinase
1.02
-
mevalonate
-
mutant E193Q, pH 7.0, 30C
1.43
-
mevalonate
-
pH 7.5, 34C, R196L mutant mevalonate kinase
1.92
-
mevalonate
-
-
2.5
-
mevalonate
-
pH 7.5, 30C, recombinant S201A mevalonate kinase
4.03
-
mevalonate
-
pH 7.5, 34C, R196V mutant mevalonate kinase
9.28
-
mevalonate
-
pH 7.5, 34C, R196Q mutant mevalonate kinase
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
-
MgATP2-
-
pH 6.5, 30C, at 1 mM Mg2+
1.75
-
MgATP2-
-
pH 7.0, 25C
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
-
RS-mevalonate
-
pH 7.0, 30C, enzyme from etiolated cotyledons
0.046
-
RS-mevalonate
-
pH 7.0, 30C, leaf enzyme
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]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
3.1
-
(R)-mevalonate
-
mutant C107S/C281S, pH 7.5, 34C
4.3
-
(R)-mevalonate
-
in 50 mM Tris, 50 mM NaCl (pH 7.6), at 30C
5.2
-
(R)-mevalonate
-
mutant A141C, pH 7.5, 34C
8.6
-
(R)-mevalonate
-
mutant C107A/C281A, pH 7.5, 34C
10.5
-
(R)-mevalonate
-
mutant C107S, pH 7.5, 34C
12.7
-
(R)-mevalonate
-
mutant C281S, pH 7.5, 34C
17.1
-
(R)-mevalonate
-
mutant C107A, pH 7.5, 34C
21.9
-
(R)-mevalonate
-
wild-type, pH 7.5, 34C
23.3
-
(R)-mevalonate
-
mutant C281A, pH 7.5, 34C
28.5
-
(R)-mevalonate
-
wild-type, pH 7.5, 34C
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
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
3.4e-05
-
farnesyl diphosphate
Q03426
wild-type, 30C, pH 7.5
3.5e-05
-
farnesyl diphosphate
-
pH 7.5, 30C
5.53e-05
-
farnesyl diphosphate
Q03426
mutant I56A, 30C, pH 7.5
6.26e-05
-
farnesyl diphosphate
Q03426
mutant Y149A, 30C, pH 7.5
7.34e-05
-
farnesyl diphosphate
Q03426
mutant L54A, 30C, pH 7.5
7.49e-05
-
farnesyl diphosphate
Q03426
mutant T104A, 30C, pH 7.5
8.57e-05
-
farnesyl diphosphate
Q03426
mutant R388X, 30C, pH 7.5
0.0001
-
farnesyl diphosphate
-
pH 7.5, 30C
0.000104
-
farnesyl diphosphate
-
pH 7.0, 25C, recombinant mevalonate kinase
0.0001807
-
farnesyl diphosphate
Q03426
mutant I196A, 30C, pH 7.5
0.00035
-
farnesyl diphosphate
-
pH 7.5, 30C
0.0013
-
farnesyl diphosphate
-
pH 7.0, 30C
0.001313
-
farnesyl diphosphate
Q03426
mutant T104A/I196A, 30C, pH 7.5
0.001713
-
farnesyl diphosphate
Q03426
mutant T104A/I196A/R388X, 30C, pH 7.5
0.002
-
farnesyl diphosphate
-
liver mevalonate kinase
0.0025
-
farnesyl diphosphate
-
pH 7.0, 25C
0.0025
-
farnesyl diphosphate
-
-
0.0052
-
farnesyl diphosphate
-
pH 7.0, 30C
0.0071
-
farnesyl diphosphate
-
pH 7.0, 30C
0.011
-
farnesyl diphosphate
-
pH 7.0, 30C
0.046
-
farnesyl diphosphate
-
pH 7.5, 30C
2.9e-05
-
farnesyl thiodiphosphate
-
pH 7.5, 30C
0.00047
-
farnesyl thiodiphosphate
-
pH 7.5, 30C
0.045
-
farnesyl thiodiphosphate
-
pH 7.5, 30C
0.002
-
geranyl diphosphate
-
liver mevalonate kinase
0.0023
-
geranyl diphosphate
-
pH 7.0, 30C
0.018
-
geranyl diphosphate
-
pH 7.0, 30C
0.028
-
geranyl diphosphate
-
pH 7.0, 30C
0.031
-
geranyl diphosphate
-
pH 7.0, 30C
0.116
-
geranyl diphosphate
-
pH 7.0, 25C, recombinant mevalonate kinase
0.116
-
geranyl diphosphate
Q03426
-
0.022
-
geranylgeranyl diphosphate
-
pH 7.0, 30C
0.049
-
geranylgeranyl diphosphate
-
pH 7.0, 30C
0.059
-
geranylgeranyl diphosphate
-
pH 7.0, 25C, recombinant mevalonate kinase
0.115
-
geranylgeranyl diphosphate
-
pH 7.0, 30C
0.016
-
isopentenyl diphosphate
-
pH 7.0, 25C, recombinant mevalonate kinase
0.0036
-
phytyl diphosphate
-
pH 7.0, 30C
0.0039
-
phytyl diphosphate
-
pH 7.0, 30C
0.009
-
phytyl diphosphate
-
pH 7.0, 30C
0.016
-
phytyl diphosphate
-
pH 7.0, 30C
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0075
-
(3R),(5S)-P'-geranyl 3,5,8-trihydroxy-3-methyloctanate 8-diphosphate
-
pH 7.0, 30C
0.0025
-
(3S),(5R)-P'-geranyl 3,5,8-trihydroxy-3-methyloctanate 8-diphosphate
-
pH 7.0, 30C
0.45
-
8-[[hydroxy(phosphonooxy)phosphoryl]oxy]octanoic acid
-
pH 7.0, 30C
0.005
-
geranyl diphosphate
-
-
0.18
-
mevalonate 5-diphosphate
-
-
0.008
-
P'-geranyl 3,5,7-trihydroxy-3-methylheptanate 7-diphosphate
-
pH 7.0, 30C
0.0038
-
P'-geranyl 3,5,8-trihydroxy-3-methyloctanate 8-diphosphate
-
pH 7.0, 30C
0.0039
-
P'-geranyl 3,5,9-trihydroxy-3-methylnonanate 9-diphosphate
-
pH 7.0, 30C
0.0055
-
P'-geranyl octanate 8-diphosphate
-
pH 7.0, 30C
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.014
-
-
-
12.4
-
-
purified enzyme, pH 7.5, 30C
17.5
-
-
-
24
-
-
purified enzyme, pH 10, 37C
30.4
-
-
-
32.7
-
-
recombinant mevalonate kinase
32.7
-
-
purified His-tag protein, pH 7.5, 25C
37
-
-
pH 7.0, 30C
387
-
-
recombinant mevalonate kinase
additional information
-
-
assay procedure
additional information
-
-
0.58 dpm/mg
additional information
-
-
0.132 dpm/mg
additional information
-
-
development of a highly sensitive radioactive assay
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7
8
-
recombinant mevalonate kinase
7
-
Q4Q6K7
assay at
8.9
-
-
broad optimum between pH 7.0 and pH 10.0
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
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
9
-
at least 80% of maximal activity over the whole range, recombinant mevalonate kinase
6.5
9
-
approx. 40% of maximal activity at pH 6.5, approx. 70% of maximal activity at pH 9.0
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
30
-
Q4Q6K7
assay ta
35
37
-
assay at
37
-
-
assay at
TEMPERATURE RANGE
TEMPERATURE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
34
-
-
wild-type, 25% of maximal activity
37
90
-
approx. 25% of maximal activity at 40C and 90C, respectively
pI VALUE
pI VALUE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
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 ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
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
-
cultured granulosa cell
Manually annotated by BRENDA team
-
cell line PLC/PRF/5
Manually annotated by BRENDA team
-
3rd instar larvae
Manually annotated by BRENDA team
-
highest expression of both mevalonate kinase and cob(I)alamin adenosyltransferase
Manually annotated by BRENDA team
-
a clonal osteoblast-like mouse calvarial cell line
Manually annotated by BRENDA team
Q9R008
from castrated mice. Treatment with androgens may promote cholesterol biosynthesis
Manually annotated by BRENDA team
-
superovulated
Manually annotated by BRENDA team
-
LPS-stimulated peripheral blood mononuclear cell
Manually annotated by BRENDA team
additional information
-
mevalonate kinase and cob(I)alamin adenosyltransferase display a similar tissue expression pattern. Their genes are located in a head-to-head formation and are suppressed by an excess of cholesterol as well as sterol regulatory element binding protein SREBP-2
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
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
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
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
32200
-
-
sedimentation velocity
33840
-
-
calculated from the deduced amino acid sequence
34500
-
-
gel filtration
64600
-
-, Q8PW39
gel filtration
68000
-
-
gel filtration
71100
-
-
sedimentation velocity, 10% of total enzyme
78000
-
-
gel filtration
78000
-
-
gel filtration
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 ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 42500, recombinant mevalonate kinase, SDS-PAGE
?
-
x * 41000, deduced from nucleotide sequence
?
-
x * 42000, SDS-PAGE, His-tag protein
?
Q980D2
x * 37000, calculated from sequence
?
-
x * 37000, calculated from sequence
-
dimer
-
2 * 52000, SDS-PAGE
dimer
-
2 * 39900, SDS-PAGE
dimer
-
2 * 42000, SDS-PAGE
dimer
-
2 * 37000, SDS-PAGE
dimer
-
2 * 41500, SDS-PAGE
dimer
-
2 * 41990, deduced from nucleotide sequence
dimer
-
-
dimer
-
2 * 42000, recombinant mevalonate kinase, SDS-PAGE
dimer
-
2 * 32200, sedimentation velocity, 10% of total enzyme
dimer
-
2 * 42000, SDS-PAGE
homodimer
-, Q8PW39
2 * 33000, SDS-PAGE; 2 * 33600, His-tagged protein, calculated from amino acid sequence
homodimer
-
2 * 35500, calculated from amino acid sequence
monomer
-
1 * 33000, SDS-PAGE and gel filtration
monomer
-
1 * 32200, sedimentation velocity, SDS-PAGE
additional information
-
enzyme is involved in post-transcriptional regulation of luteinizing hormone receptor
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
free enzyme, 2.5 A resolution. Modeling of complex with farnesyl thiophosphate
Q03426
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
Q4Q6K7
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
-, Q8PW39
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
pH STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
4.5
9
-
1 h, no loss of activity
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
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%
50
-
-
1 h, little inactivation
50
-
-
rate constant for inactivation of wild-type and V377I mevalonate kinase: 0.026 and 0.031/min
50
-
-
approx. 50% and 90% loss of activity after 10 min and 30 min, respectively, H20P/V377I double mutant is only slightly more temperature sensitive
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 ACCESSION NO.
LITERATURE
sensitive to dialysis
-
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
-
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
5C, stable for several months in buffer containing dithiothreitol
-
-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
-
-10C, several months, no loss of activity
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
ammonium sulfate, Sephadex G-100, DEAE-Sephadex
-
Q-Sepharose, Phenyl-Sepharose, Mono Q, Shodex KW 803
-
recombinant protein using His-tag
-
precipitation at pH 4.5, Sephadex G-200, DEAE-Sephadex
-
recombinant enzyme
-
recombinant mevalonat kinase-glutathione S-transferase fusion protein, glutathione Sepharose beads
-
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography, dialysis, and anion exchange chromatography to homogeneity
Q4Q6K7
recombinant mevalonate kinase, 70C heat treatment, Talon metal-affinity resin
-
HiTrap IMAC column chromatography and HiTrap Q column chromatography
-
Ni-NTA bead column chromatography, Resource 15Q column chromatography, and Superdex 200 gel filtration
-, Q8PW39
ammonium sulfate, protamine sulfate, ammonium sulfate, DEAE-cellulose
-
enzyme from cotyledons and leaves, ammonium sulfate, Sephadex G-200, DEAE-Sephadex
-
ammonium sulfate, Sephadex G-100
-
protamine sulfate, ammonium sulfate, Sephadex G-100
-
ammonium sulfate, Blue-Sepharose, ammonium sulfate, Sephadex G-150, ATP-agarose
-
recombinant His-tagged mevalonate kinase, hiTrap column
-
recombinant mevalonate kinase, Fast Q, Phenyl-agarose
-
recombinant proteins using His-tag
-
protamine sulfate, ammonium sulfate, acid treatment at pH 5.0, ammonium sulfate
-
recombinant enzyme
-
recombinant dual-tagged His6-GST enzyme from Escherichia coli by affinity chromatography
Q8DR51
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
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expressed as His-tag fusion protein in Escherichia coli BL21(DE3)
-
expression in Escherichia coli
-
expressed in HEK293 Flp-In and CV1 Flp-In cells
-
expression in Escherichia coli
-
expression of wild-type and N301T mutant mevalonate kinase in COS-7 cells
Q03426
gene MVK, location on chromosome 12q24
-
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
Q4Q6K7
expression in Trypanosoma brucei
-
overexpression in Escherichia coli
-
expressed in Escherichia coli BL21 Star (lambdaDE3) cells
-
expressed in Escherichia coli BL21(DE3) cells
-, Q8PW39
expression in 293T cell
-
expression in Escherichia coli
-
expression of His-tagged mevalonate kinase in Escherichia coli
-
native and mutant enzymes expressed as His-tag fusion proteins in Escherichia coli BL21(DE3)
-
cloning of ERG12 gene
-
expressed in Escherichia coli BL21(DE3)
-
overexpression in Escherichia coli as dual-tagged His6-GST fusion protein
Q8DR51
expression in Escherichia coli
Q980D2
DNA and amino acid sequence determination and anaylsis, overexprssion in a procyclic form of Trypanosoma brucei
-
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
parathyroid hormone, from human source comprising residues 1-34, suppresses the mevalonate kinase in osteoblastic cells
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
A148T
Q03426
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
Q03426
markedly decreased mevalonate kinase activity when expressed in Escherichia coli
I196A
Q03426
modest changes in Km and Ki values
I268T
Q03426
markedly decreased mevalonate kinase activity when expressed in Escherichia coli
I268T
-
leads in homozygous state to mevalonic aciduria, inactive mevalonate kinase
I56A
Q03426
4.5fold increase in Km value for ATP
L264F
Q03426
markedly decreased mevalonate kinase activity when expressed in Escherichia coli
L265P
Q03426
markedly decreased mevalonate kinase activity when expressed in Escherichia coli
N301T
Q03426
5-20% of wild-type activity
P165L
Q03426
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
Q03426
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
Q03426
modest changes in Km and Ki values
T104A/I196A
Q03426
39fold increase in Ki value
T104A/I196A/R388X
Q03426
11fold increase in Km value for mevalonate
T243A
-
39% of wild-type activity
T243I
Q03426
markedly decreased mevalonate kinase activity when expressed in Escherichia coli
V310M
Q03426
markedly decreased mevalonate kinase activity when expressed in Escherichia coli
V377I
Q03426
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
Q03426
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
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
L53A
Q03426
modest changes in Km and Ki values
additional information
-
mutations in the mevalonate kinase gene cause the hyperimmunoglobulin D syndrome, HIDS, an autosomal recessive autoinflammatory disease, phenotype
R196V
-
60% of wild-type activity
additional information
-
deletion of one mevalonate kinase allele yields viable mice with significantly reduced liver mevalonate kinase enzyme activity. Cholesterol levels in tissues and blood, and isoprene end-products ubiquinone and dolichol in tissues are normal in Mvk+/- mice. Mevalonate concentrations are increased in spleen, heart, and kidney yet normal in brain and liver. While the trend is for higher IgA levels in Mvk+/- sera, IgD levels are significantly increased and the animals show increased serum tumor necrosis factor-alpha levels
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
medicine
-
potential target for drugs
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
diagnostics
-
mutations in the mevalonate kinase gene cause the hyperimmunoglobulin D syndrome, HIDS, and are an appropriate marker for the disease
medicine
-
no significant correlation between mutations in the mevalonate kinase gene and Behcet's disease. Of 97 patients, two had paired mutations in the mevalonate kinase gene and displayed typical features of Behcet's disease and mevalonate kinase deficiency
medicine
-
inhibition of HMG-CoA reductase by simvastatin treatment of LPS-stimulated peripheral blood mononuclear cells mimicks mevalonate kinase deficiency and results in increased interleukin-1beta secretion in Rac1/phosphatidylinositol-3 kinase-dependent manner. Results suggest that in mevalonate kinase deficiency, dysregulated isoprenoid biosynthesis activates Rac1/phosphatidylinositol-3 kinase/PKB resulting in caspase-1 activation with increased interleukin-1beta processing and release. Inhibition of Rac1 in LPS-stimulated peripheral blood mononuclear cells from patients with mevalonate kinase deficiency results in dramatic reduction in interleukin-1beta release
medicine
-
patient with hyperimmunoglobulinemia D due to mutations of the gene coding for mevalonatekinase, and periodic fever syndrome. Treatment with etanercept with a dose of 0.8 mg/kg per week results in great improvement of both attacks and acute-phase response but with still persistent massive hepatosplenomegaly
medicine
-
patients with hyperimmunoglobulinemia D and periodic fever syndrome due to mutations V377I/I268T. Patients developed significant B cell cytopenia with hypogammaglobulinemia. Therapy of prednisone, azathioprine, and intravenous immunoglobulins resulted in reduced incidence and severity of febrile attacks
medicine
-
case study of patients with mevalonic aciduria. Patients display high urinary excretion of mevalonic acid. After the second year of life they developed mental retardation, ataxia and hypotonia as well as cerebellar atrophy of both hemispheres and vermis
medicine
-
inhibition of the isoprenoid pathway results in a dose-dependent reduction of amyloid formed. The inhibitory effects of lovastatin are reversible by addition of farnesol but not geranylgeraniol. Farnesyl transferase inhibition also inhibits amyloidogenesis
medicine
-
severe case of mevalonate kinase deficiency associated with nephritis. Patient is homozygous for mutation G336S, catalytic activity of the mutant enzyme is less than 1% of wild-type activity. Laboratory data obtained in a period of well-being show increased values of markers of inflammation, severe anemia, and high serum IgA values. Serum autoantibodies are undetectable. Treatment with interleukin 1 receptor antagonist anakinra resulted in normalization of the C-reactive protein, a rise in the hemoglobin value, and disappearance of proteinuria. Hematuria disappeared after 2 months of treatment
medicine
-
clinical relevance of the measurement of IgD for diagnosis of mevalonate kinase deficiency is poor
medicine
-
patient with mevalonate kinase deficiency due to mutation Q390P and a four-base deletion c.475-478 delACTG. Patient shows high serum immunoglobulin D, elevated mevalonaciduria and low mevalonate kinase activity in lymphocytes. Patient was treated with subcutaneous doses of anakinra. Most disease manifestations regressed dramatically and no new flares have occurred
medicine
-
mouse model for typical mevalonate kinase deficiency can be obtained by treatment of BALB/c mice with aminobisphosphonate alendronate and bacterial muramyldipeptide. Exogenous isoprenoids geraniol, farnesol and geranylgeraniol are effective in prevention of the inflammation induced by alendronate/muramyldipeptide
medicine
-
luteinizing hormone receptor mRNA is up-regulated due to increased stability when estrogen negatively controls mevalonate kinase