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Information on EC 1.1.1.88 - hydroxymethylglutaryl-CoA reductase
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EC Tree
1.1.1.88 hydroxymethylglutaryl-CoA reductaseSpecify your search results
Word Map
- 1.1.1.88
- cholesterol
- statin
- lipoprotein
- simvastatin
- sterol
-
low-density
- coronary
- cardiovascular
- lovastatin
- hypercholesterolemia
- pravastatin
- atorvastatin
-
lipid-lowering
-
cholesterol-lowering
- 3-hydroxy-3-methylglutaryl-coa
- cerivastatin
- mevinolin
-
alpha-hydroxylase
-
statin-induced
- compactin
- mevalonolactone
- cholestyramine
- mevalonii
-
lipoprotein-deficient
- medicine
- 25-hydroxycholesterol
-
fibric
The expected taxonomic range for this enzyme is: Bacteria, Archaea, Eukaryota
Reaction Schemes
+
+
2
=
+
2
+
2
Synonyms
hydroxymethylglutaryl-coa reductase, hydroxymethylglutaryl coenzyme a reductase, 3-hydroxy-3-methylglutaryl-coenzyme-a reductase, 3-hydroxy-3-methylglutaryl coa reductase 1, mt hmgr1, nadh-dependent hmg-coa reductase, 
more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
3-hydroxy-3-methylglutaryl coenzyme A reductase
beta-hydroxy-beta-methylglutaryl CoA-reductase
-
-
-
-
beta-hydroxy-beta-methylglutaryl coenzyme A reductase
-
-
-
-
HMG-CoA reductase
HMGR
hydroxymethylglutaryl coenzyme A reductase
-
-
-
-
NADH-dependent HMG-CoA reductase
3-hydroxy-3-methylglutaryl coenzyme A reductase
-
-
-
-
HMG-CoA reductase
-
-
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
(R)-mevalonate + CoA + 2 NAD+ = 3-hydroxy-3-methylglutaryl-CoA + 2 NADH + 2 H+
reaction mechanism purposal
-
(R)-mevalonate + CoA + 2 NAD+ = 3-hydroxy-3-methylglutaryl-CoA + 2 NADH + 2 H+
There are two classes of enzyme, the third enzyme of the mevalonate pathway of isopentenyl diphosphate biosynthesis: the class I enzymes of eukaryotes and the class II enzymes of certain eubacteria
-
(R)-mevalonate + CoA + 2 NAD+ = 3-hydroxy-3-methylglutaryl-CoA + 2 NADH + 2 H+
-
-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
-
-
-
-
oxidative acylation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
reductive deacylation
-
-
-
-
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PATHWAY SOURCE
PATHWAYS
BRENDA
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SYSTEMATIC NAME
IUBMB Comments
(R)-mevalonate:NAD+ oxidoreductase (CoA-acylating)
-
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CAS REGISTRY NUMBER
COMMENTARY
37250-24-1
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(R)-mevalonate + CoA + NADP+
3-hydroxy-3-methylglutaryl-CoA + NADPH + H+
-
-
-
-
r
3-hydroxy-3-methylglutaryl-CoA + 2 NADPH + 2 H+
(R)-mevalonate + CoA + 2 NADP+
-
extremely low activity with NADPH
-
-
?
DL-mevaldate + CoA + NAD+
3-hydroxy-3-methylglutaryl-CoA NADH + H+
-
-
-
-
r
DL-mevaldate + CoA + NAD+
4-hydroxy-3-methylglutaryl-CoA NADH + H+
-
-
-
-
r
DL-mevaldate + CoA + NAD+
5-hydroxy-3-methylglutaryl-CoA NADH + H+
-
-
-
-
r
(R)-mevalonate + CoA + 2 NAD+
(S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADH + 2 H+
-
-
-
r
(R)-mevalonate + CoA + 2 NAD+
(S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADH + 2 H+
NAD(H) is the preferred cofactor
-
-
r
(R)-mevalonate + CoA + 2 NAD+
(S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADH + 2 H+
-
-
-
-
?
(R)-mevalonate + CoA + 2 NAD+
(S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADH + 2 H+
-
-
-
-
?
(R)-mevalonate + CoA + 2 NAD+
(S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADH + 2 H+
-
-
-
-
?
(R)-mevalonate + CoA + 2 NAD+
(S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADH + 2 H+
-
-
-
-
?
(R)-mevalonate + CoA + 2 NAD+
(S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADH + 2 H+
-
-
-
-
?
(R)-mevalonate + CoA + 2 NAD+
(S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADH + 2 H+
-
-
-
-
r
(R)-mevalonate + CoA + 2 NAD+
(S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADH + 2 H+
-
with mevalonate as sole source of carbon enzyme acts as a biodegradative enzyme
-
-
?
(R)-mevalonate + CoA + 2 NAD+
(S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADH + 2 H+
-
with mevalonate as sole source of carbon enzyme acts as a biodegradative enzyme
-
-
r
(R)-mevalonate + CoA + 2 NAD+
3-hydroxy-3-methylglutaryl-CoA + 2 NADH + 2 H+
-
-
-
-
r
(R)-mevalonate + CoA + 2 NAD+
3-hydroxy-3-methylglutaryl-CoA + 2 NADH + 2 H+
-
-
-
?
(R)-mevalonate + CoA + 2 NAD+
3-hydroxy-3-methylglutaryl-CoA + 2 NADH + 2 H+
Burkholderia cenocepacia 32315
-
-
-
?
(R)-mevalonate + CoA + 2 NAD+
3-hydroxy-3-methylglutaryl-CoA + 2 NADH + 2 H+
-
-
-
-
r
(R)-mevalonate + CoA + 2 NAD+
3-hydroxy-3-methylglutaryl-CoA + 2 NADH + 2 H+
-
-
-
-
r
(S)-3-hydroxy-3-methylglutaryl-CoA + NADH + H+
(R)-mevalonate + NAD+ + CoA
-
mevalonate is required for cholesterol and isoprenoid synthesis
-
-
?
(S)-3-hydroxy-3-methylglutaryl-CoA + NADH + H+
(R)-mevalonate + NAD+ + CoA
-
-
-
-
?
(S)-3-hydroxy-3-methylglutaryl-CoA + NADH + H+
(R)-mevalonate + NAD+ + CoA
-
mevalonate is first commited intermediate in polyisoprenoid synthesis
-
-
?
3-hydroxy-3-methyl-glutaryl-CoA + NADH + H+
mevalonate + CoA + NAD+
-
-
-
-
?
3-hydroxy-3-methyl-glutaryl-CoA + NADH + H+
mevalonate + CoA + NAD+
-
mevalonate pathway
-
-
?
3-hydroxy-3-methyl-glutaryl-CoA + NADH + H+
mevalonate + CoA + NAD+
-
-
-
-
?
3-hydroxy-3-methylglutaryl-CoA + 2 NADH + 2 H+
(R)-mevalonate + CoA + 2 NAD+
-
-
-
-
?
3-hydroxy-3-methylglutaryl-CoA + 2 NADH + 2 H+
(R)-mevalonate + CoA + 2 NAD+
-
the enzyme is highly specific for NADH
-
-
?
3-hydroxy-3-methylglutaryl-CoA + NADH + H+
mevalonate + CoA + NAD+
-
-
-
-
?
3-hydroxy-3-methylglutaryl-CoA + NADH + H+
mevalonate + CoA + NAD+
-
-
-
-
r
DL-mevalonate + CoA + NADP+
3-hydroxy-3-methylglutaryl-CoA + NADPH + H+
-
-
-
-
r
DL-mevalonate + CoA + NADP+
3-hydroxy-3-methylglutaryl-CoA + NADPH + H+
-
-
-
-
r
additional information
?
-
the substrates of the reductive reaction, HMG-CoA and NADH, both demonstrate sigmoidal behavior typical of positive cooperativity
-
-
?
additional information
?
-
-
The enzyme can play a role in indole alkaloid biosynthesis and a possible cosuppression of both the endogenous and foreign enzyme genes in clone 236
-
-
?
additional information
?
-
-
oxidative acylation of mevalonate: the carboxy-, 3-methyl-, and 3-hydroxy groups are essential for substrate binding to the enzyme
-
-
?
additional information
?
-
-
oxidative acylation of mevalonate: the carboxy-, 3-methyl-, and 3-hydroxy groups are essential for substrate binding to the enzyme
-
-
?
additional information
?
-
-
oxidative acylation of mevalonate: the carboxy-, 3-methyl-, and 3-hydroxy groups are essential for substrate binding to the enzyme
-
-
?
additional information
?
-
-
oxidative acylation of mevalonate: the carboxy-, 3-methyl-, and 3-hydroxy groups are essential for substrate binding to the enzyme
-
-
?
additional information
?
-
-
The biosynthetic pathway leading to plant cytosolic isoprenoids begins with the 3-hydroxy-3-methyl-glutaryl CoA reductase-mediated production of mevalonate
-
-
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
3-hydroxy-3-methyl-glutaryl-CoA + NADH + H+
mevalonate + CoA + NAD+
-
mevalonate pathway
-
-
?
(R)-mevalonate + CoA + 2 NAD+
(S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADH + 2 H+
-
-
-
r
(R)-mevalonate + CoA + 2 NAD+
(S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADH + 2 H+
-
-
-
-
?
(R)-mevalonate + CoA + 2 NAD+
3-hydroxy-3-methylglutaryl-CoA + 2 NADH + 2 H+
-
-
-
-
r
(R)-mevalonate + CoA + 2 NAD+
3-hydroxy-3-methylglutaryl-CoA + 2 NADH + 2 H+
-
-
-
?
(R)-mevalonate + CoA + 2 NAD+
3-hydroxy-3-methylglutaryl-CoA + 2 NADH + 2 H+
Burkholderia cenocepacia 32315
-
-
-
?
(R)-mevalonate + CoA + 2 NAD+
3-hydroxy-3-methylglutaryl-CoA + 2 NADH + 2 H+
-
-
-
-
r
(R)-mevalonate + CoA + 2 NAD+
3-hydroxy-3-methylglutaryl-CoA + 2 NADH + 2 H+
-
-
-
-
r
(S)-3-hydroxy-3-methylglutaryl-CoA + NADH + H+
(R)-mevalonate + NAD+ + CoA
-
mevalonate is required for cholesterol and isoprenoid synthesis
-
-
?
(S)-3-hydroxy-3-methylglutaryl-CoA + NADH + H+
(R)-mevalonate + NAD+ + CoA
-
-
-
-
?
(S)-3-hydroxy-3-methylglutaryl-CoA + NADH + H+
(R)-mevalonate + NAD+ + CoA
-
mevalonate is first commited intermediate in polyisoprenoid synthesis
-
-
?
3-hydroxy-3-methylglutaryl-CoA + 2 NADH + 2 H+
(R)-mevalonate + CoA + 2 NAD+
-
-
-
-
?
3-hydroxy-3-methylglutaryl-CoA + 2 NADH + 2 H+
(R)-mevalonate + CoA + 2 NAD+
-
the enzyme is highly specific for NADH
-
-
?
additional information
?
-
-
The enzyme can play a role in indole alkaloid biosynthesis and a possible cosuppression of both the endogenous and foreign enzyme genes in clone 236
-
-
?
additional information
?
-
-
The biosynthetic pathway leading to plant cytosolic isoprenoids begins with the 3-hydroxy-3-methyl-glutaryl CoA reductase-mediated production of mevalonate
-
-
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
NADP+
-
NAD+ is 600000fold more efficient than NADP+ in wild-type enzyme
NAD+
-
-
287495, 287496, 287497, 287498, 287499, 287501, 287502, 287504, 287505, 287506, 287508, 657303, 723092
NADH
-
reverse reaction
additional information
-
very detailed kinetic studies of mutants concerning NAD+/NADP+-affinities, the best specificity improvement is achieved by the D146A/L148R-mutant
-
additional information
-
sequence comparisons of several species with class II (NAD(H)) and class I (NADP(H)) HMG-CoA reductases for analysis of cofactor binding, overview
-
additional information
-
sequence comparisons of several species with class II (NAD(H)) and class I (NADP(H)) HMG-CoA reductases for analysis of cofactor binding, overview
-
additional information
-
sequence comparisons of several species with class II (NAD(H)) and class I (NADP(H)) HMG-CoA reductases for analysis of cofactor binding, specificity-determining residue of HMGR from Pseudomonas mevalonii is D646, overview
-
additional information
the enzyme prefers NAD(H) over NADP(H) as a cofactor, suggesting an oxidative physiological role for the enzyme
-
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(3S,6Z)-3-benzyl-1-(4-fluorobenzyl)-8-(4-methoxyphenyl)-4-(3-methylbutanoyl)-3,4,5,8-tetrahydro-1,4-diazocin-2(1H)-one
(3S,6Z)-3-benzyl-1-(4-fluorobenzyl)-8-(4-methoxyphenyl)-4-[[(E)-2-phenylethenyl]sulfonyl]-3,4,5,8-tetrahydro-1,4-diazocin-2(1H)-one
(3S,6Z)-3-benzyl-4-(3,3-dimethylbutanoyl)-1-(4-fluorobenzyl)-8-(4-methoxyphenyl)-3,4,5,8-tetrahydro-1,4-diazocin-2(1H)-one
(3S,6Z)-4-(biphenyl-4-ylsulfonyl)-1-(4-fluorobenzyl)-8-(4-methoxyphenyl)-3-methyl-3,4,5,8-tetrahydro-1,4-diazocin-2(1H)-one
citrate
-
competitive inhibition with respect to 3-hydroxy-3-methylglutaryl-CoA
lovastatin
-
pharmacological inhibition of HMGR activities decreases nodule number and delays nodulation
simvastatin
-
treatment prevents endotoxemic liver injury by inhibiting leukocyte infiltration and hepatocellular apoptosis. The protective effects are dependent on the 3-hydroxy-3-methylglutaryl-coenzyme A reductase pathway
(3S,6Z)-3-benzyl-1-(4-fluorobenzyl)-8-(4-methoxyphenyl)-4-(3-methylbutanoyl)-3,4,5,8-tetrahydro-1,4-diazocin-2(1H)-one
-
purified enzyme, 52.6% residual activity at 0.01 mM
(3S,6Z)-3-benzyl-1-(4-fluorobenzyl)-8-(4-methoxyphenyl)-4-(3-methylbutanoyl)-3,4,5,8-tetrahydro-1,4-diazocin-2(1H)-one
-
antiproliferative activity in L-1210 cell, IC50 0.00148 mM
(3S,6Z)-3-benzyl-1-(4-fluorobenzyl)-8-(4-methoxyphenyl)-4-[[(E)-2-phenylethenyl]sulfonyl]-3,4,5,8-tetrahydro-1,4-diazocin-2(1H)-one
-
purified enzyme, 32.3% residual activity at 0.01 mM
(3S,6Z)-3-benzyl-1-(4-fluorobenzyl)-8-(4-methoxyphenyl)-4-[[(E)-2-phenylethenyl]sulfonyl]-3,4,5,8-tetrahydro-1,4-diazocin-2(1H)-one
-
antiproliferative activity in L-1210 cell, IC50 0.0023 mM
(3S,6Z)-3-benzyl-4-(3,3-dimethylbutanoyl)-1-(4-fluorobenzyl)-8-(4-methoxyphenyl)-3,4,5,8-tetrahydro-1,4-diazocin-2(1H)-one
-
purified enzyme, 43.4% residual activity at 0.01 mM
(3S,6Z)-3-benzyl-4-(3,3-dimethylbutanoyl)-1-(4-fluorobenzyl)-8-(4-methoxyphenyl)-3,4,5,8-tetrahydro-1,4-diazocin-2(1H)-one
-
antiproliferative activity in L-1210 cell, IC50 0.00143 mM
(3S,6Z)-4-(biphenyl-4-ylsulfonyl)-1-(4-fluorobenzyl)-8-(4-methoxyphenyl)-3-methyl-3,4,5,8-tetrahydro-1,4-diazocin-2(1H)-one
-
purified enzyme, 54.4% residual activity at 0.01 mM
(3S,6Z)-4-(biphenyl-4-ylsulfonyl)-1-(4-fluorobenzyl)-8-(4-methoxyphenyl)-3-methyl-3,4,5,8-tetrahydro-1,4-diazocin-2(1H)-one
-
antiproliferative activity in L-1210 cell, IC50 0.00119 mM
acetoacetate
-
competivive inhibitor vs. mevalonate, non inhibitory vs. NAD+
mevalonate
-
the addition of reaction product results in a dramatic loss of immunoreactive enzyme
additional information
-
peptic and tryptic soybean hydrolysates (2.5 mg/ml) inhibit the 3-hydroxy-3-methylglutaryl-CoA reductase activity in Hep-G2 cells by 16% and 76.9%, respectively
-
additional information
-
no inhibition citrate, succinate, glutarate, 3,3-dimethylacrylate, 2,2-dimethylpropionate, acetoacetate
-
additional information
-
no inhibition citrate, succinate, glutarate, 3,3-dimethylacrylate, 2,2-dimethylpropionate, acetoacetate
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
docosahexaenoic acid ethyl ester
-
in 18-month-old aged mice but not in 8-month-old mice, HMG-CoA reductase activity is enhanced with dietary intake of docosahexaenoic acid ethyl ester (DHA-EE)
mevastatin
-
The increased accumulation of the enzyme-FLAG using the open-ring form and the closed-ring form of mevastatin is observed. The mevastatin-induced enzyme increases are possibly explained by the inhibition of a feedback-regulated down-regulation due to lowered pools of mevalonate or its product
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.078
(S)-3-hydroxy-3-methylglutaryl-CoA
pH and temperature not specified in the publication
0.00734
3-hydroxy-3-methylglutaryl-CoA
-
at pH 7.4, temperature not specified in the publication
additional information
additional information
kinetic analysis, overview. The enzyme exhibits positive cooperativity toward the substrates of the reductive reaction, but the oxidative reaction exhibits unusual double-saturation kinetics, distinctive among characterized HMG-CoA reductases. The unusual kinetics may arise from the presence of multiple active oligomeric states, each with different Vmax values
-
0.27
(R,S)-mevalonate
-
H381A mutant, oxidative acylation of mevalonate
0.45
(R,S)-mevalonate
-
wild-type enzyme, oxidative acylation of mevalonate
0.71
(R,S)-mevalonate
-
H381Q mutant, oxidative acylation of mevalonate
0.75
(R,S)-mevalonate
-
H381K mutant, oxidative acylation of mevalonate
0.05
DL-3-hydroxy-3-methylglutaryl-CoA
-
reductive deacylation to mevalonate
0.3
DL-3-hydroxy-3-methylglutaryl-CoA
-
reductive deacylation to mevalonate
0.072
NADH
pH and temperature not specified in the publication
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
22.3
3-hydroxy-3-methylglutaryl-CoA
-
at pH 7.4, temperature not specified in the publication
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
3040
3-hydroxy-3-methylglutaryl-CoA
-
at pH 7.4, temperature not specified in the publication
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
4.5
3-hydroxy-3-methylglutarate
-
standard conditions, inhibition by substrate analog
35
4-hydroxybutyrate
-
standard conditions, inhibition by substrate analog
0.8
beta-hydroxybutyrate
-
standard conditions, inhibition by substrate analog
0.53
lovastin
-
competive inhibition with respect to 3-hydroxy-3-methylglutaryl-CoA
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
90
simvastatin acid
Burkholderia cenocepacia
pH and temperature not specified in the publication
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
after a dietary intake of docosahexaenoic acid ethyl ester (DHA-EE) brain HMG-CoA reductase activity and brain cholesterol content significantly increases with age. Hepatic HMG-CoA reductase activity and the cholesterol content of both adult and aged mice are reduced in DHA-EE diet groups compared with linoleic acid ethyl ester
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.1
7.9
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
a transgenic potato cell culture system expressing an epitope-tagged enzyme
-
-
brenda
-
-
-
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
results show that docosahexaenoic acid ethyl ester enhances brain HMG-CoA reductase activity in aged mice
brenda
-
human trophoblast cell line (JAR) infected with Chlamydia trachomatis reveal a decrease in cellular cholesterol and a down regulation of HMG-CoA reductase
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
-
found predominantly in vesicle-like structures
-
brenda
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
a key enzyme in endogenous cholesterol biosynthesis in mammals and isoprenoid biosynthesis via the mevalonate pathway in other eukaryotes, archaea and some eubacteria
physiological function
additional information
physiological function
-
HMG-CoAR increase is crucial for muscle differentiation induction. p21waf, whose increase is a necessary requisite for differentiation to occur, rises downstream HMG-CoAR activation, while p38/MAPK has a role as key regulator also for HMG-CoAR
physiological function
the enzyme prefers NAD(H) over NADP(H) as a cofactor, suggesting an oxidative physiological role for the enzyme. Also, the Burkholderia cenocepacia genome lacks the genes for the downstream enzymes of the mevalonate pathway, but the organism clearly possesses the genes for all the DXP pathway enzymes, further supporting a nonreductive, non-biosynthetic role for BcHMGR
additional information
-
sequence comparisons of several species with class II and class I HMG-CoA reductases for analysis of cofactor binding, overview
additional information
-
sequence comparisons of several species with class II and class I HMG-CoA reductases for analysis of cofactor binding, overview
additional information
-
sequence comparisons of several species with class II and class I HMG-CoA reductases for analysis of cofactor binding, overview
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hexamer
homotrimer
3 * 48000, recombinant His6-tagged enzyme, SDS-PAGE, 3 * 47458, sequence calculation and mass spectrometry
additional information
the enzyme might exist as trimer, and forms oligomers of trimers, overview
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
some minor oxidation of Met residues is detected in the trypsin-digested protein, particularly at Met343 and Met345, but no other significant post-translational modification of the enzyme could be detected
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
enzyme in the hexameric state bound to coenzyme A and ADP, hanging drop vapor diffusion method, using 0.2 M potassium acetate (pH 7.5) and 20% (w/v) PEG 3350
apoenzyme, sitting drop vapor diffusion method, using 100 mM Bis-Tris (pH 5.5), 600 mM lithium sulfate, and 18% (w/v) PEG 3350. Mevalonate-bound enzyme, sitting drop vapor diffusion method, using 100 mM Bis-Tris (pH 6.5), 600 mM lithium sulfate, and 19% (w/v) PEG 3350. NADH-bound enzyme, sitting drop vapor diffusion method, using 100 mM sodium citrate (pH 5.0), 500 mM ammonium sulfate, and 600 mM lithium sulfate
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3 A resolution, 3 dimers packed along three-fold crystallographic axis, hexamer
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wild-type and mutants, H381A, H381N, H381K, H381Q, 3 A resolution
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
H381K
H381N
H381Q
additional information
additional information
-
decreasing HMGR1 expression in Medicago truncatula transgenic roots by RNA interference leads to a dramatic decrease in nodulation, confirming that HMGR1 is essential for nodule development
additional information
-
using Medicago truncatula NORK, a receptor-like kinase, as bait in a yeast two-hybrid assay, Mt HMGR1 is identified as a NORK interacting partner. Mutagenesis and deletion analysis show that this interaction requires the cytosolic active kinase domain of NORK and the cytosolic catalytic domain of HMGR1
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His6-tagged enzyme by nickel affinity chromatography and gel filtration
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
BcHMGR is encoded by a gene between bases 588787 and 590073 on chromosome 2 of the Burkholderia cenocepacia genome, severe rare codon issues occur resulting in truncation products at 23 kD and 35 kD in addition to the expected size of 47.3 kD, successful recombinant expression of His6-tagged enzyme in Escherichia coli
expression in Catharanthus roseus, the hairy roots with higher levels of soluble enzyme, clone 19, have a lower alkaloid and higher sterol content. By contrast, the clone with nonsoluble enzyme activity, clone 236, has a higher alkaloid and lower sterol content
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
during myoblast differentiation, insulin-induced increase in protein levels is detected after 6 h, remains constant up to 16 h, and then decreases below control levels at 72 h after insulin addition
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mRNA levels of HMG-CoA-R are increased significantly in both primary and recurrent pterygia by 4.2fold and 3.6fold respectively, compared with normal conjunctiva. Concomitantly, there is a significant increase of LDL-R mRNA levels of 4.1fold in primary pterygia and 2.7fold in recurrent pterygium, compared with the control normal conjunctiva
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RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
after inactivation with diethyl polycarbonate addition of hydroxylamine restores 50% of activity
-
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
-
in endotoxemic mice, leukocyte infiltration in the liver is significantly elevated. Simvastatin significantly reduces endotoxin-induced hepatocellular damage and apoptosis. Hepatic accumulation of leukocytes is attenuated by simvastatin. Co-administration of mevalonate abolishes the protective effects of simvastatin on endotoxin-provoked increases in serum alanine transferase and serum alanine transferase as well as leukocyte recruitment
medicine
-
pterygium has an altered metabolism of cholesterol, namely increased LDL-R and HMG-CoA-R mRNAs. Both genes may play important roles in the pathogenesis of pterygium
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Fimognari, G.M.; Rodwell, V.W.
Substrate-competitive inhibition of bacterial mevalonate:nicotinamide-adenine dinucleotide oxidoreductase (acylating CoA)
Biochemistry
4
2086-2090
1965
Mycobacterium sp., Pseudomonas mevalonii, Mycobacterium sp. s4
-
brenda
Bensch, W.R.; Rodwell, V.W.
Purification and properties of 3-hydroxy-3-methylglutaryl coenzyme A reductase from Pseudomonas
J. Biol. Chem.
245
3755-3762
1970
Pseudomonas mevalonii
brenda
Rodwell, V.W.; Bensch, W.R.
S-3-Hydroxy-3-methylglutaryl-CoA reductase from Pseudomonas
Methods Enzymol.
71
480-486
1981
Pseudomonas mevalonii
brenda
Gill, J.F.; Beach, M.J.; Rodwell, V.W.
Mevalonate utilization in Pseudomonas sp. M. Purification and characterization of an inducible 3-hydroxy-3-methylglutaryl coenzyme A reductase
J. Biol. Chem.
260
9393-9398
1985
Pseudomonas mevalonii
brenda
Jordan-Starck, T.C.; Rodwell, V.W.
Pseudomonas mevalonii 3-hydroxy-3-methylglutaryl-CoA reductase. Characterization and chemical modification
J. Biol. Chem.
264
17913-17918
1989
Pseudomonas mevalonii
brenda
Jordan-Starck, T.C.; Rodwell, V.W.
Role of cysteine residues in Pseudomonas mevalonii 3-hydroxy-3-methylglutaryl-CoA reductase. Site-directed mutagenesis and characterization of the mutant enzymes
J. Biol. Chem.
264
17919-17923
1989
Pseudomonas mevalonii
brenda
Beach, M.J.; Rodwell, V.W.
Cloning, sequencing, and overexpression of mvaA, which encodes Pseudomonas mevalonii 3-hydroxy-3-methylglutaryl coenzyme A reductase
J. Bacteriol.
171
2994 - 3001
1989
Pseudomonas mevalonii
brenda
Darnay, B.G.; Wang, Y.; Rodwell, V.W.
Identification of the catalytically important histidine of 3-hydroxy-3-methylglutaryl-coenzyme A reductase
J. Biol. Chem.
267
15064-15070
1992
Pseudomonas mevalonii
brenda
Sato, R.; Goldstein, J.L.; Brown, M.S.
Replacement of serine-871 of hamster 3-hydroxy-3-methylglutaryl-CoA reductase prevents phosphorylation by AMP-activated kinase and blocks inhibition of sterol synthesis induced by ATP depletion
Proc. Natl. Acad. Sci. USA
90
9261-9265
1993
Mesocricetus auratus
brenda
Lawrence, C.M.; Rodwell, V.W.; Stauffacher, C.V.
Crystal structure of Pseudomonas mevalonii HMG-CoA reductase at 3.0 Angstrom resolution
Science
268
1758-1762
1995
Pseudomonas mevalonii
brenda
Friesen, J.A.; Lawrence, C.M.; Stauffacher, C.V.; Rodwell, V.W.
Structural determinants of nucleotide coenzyme specificity in the distinctive dinucleotide binding fold of HMG-CoA reductase from Pseudomonas mevalonii
Biochemistry
35
11945-11950
1996
Pseudomonas mevalonii
brenda
Rogers, K.S.; Rodwell, V.W.; Geiger, P.
Active form of Pseudomonas mevalonii 3-hydroxy-3-methylglutaryl coenzyme A reductase
Biochem. Mol. Med.
61
114-120
1997
Pseudomonas mevalonii
brenda
Tabernero, L.; Bochar, D.A.; Rodwell, V.W.; Stauffacher, C.V.
Substrate-induced closure of the flap domain in the ternary complex structures provides insights into the mechanism of catalysis by 3-hydroxy-3-methylglutaryl-CoA reductase
Proc. Natl. Acad. Sci. USA
96
7167-7177
1999
Pseudomonas mevalonii (P13702)
brenda
Bochar, D.A.; Tabernero, L.; Stauffacher, C.V.; Rodwell, V.W.
Aminoethylcysteine can replace the function of the essential active site lysine of Pseudomonas mevalonii 3-hydroxy-3-methylglutaryl coenzyme A reductase
Biochemistry
38
8879-8883
1999
Pseudomonas mevalonii
brenda
Ayora-Talavera, T.; Chappell, J.; Lozoya-Gloria, E.; Loyola-Vargas, V.M.
Overexpression in Catharanthus roseus hairy roots of a truncated hamster 3-hydroxy-3-methylglutaryl-CoA reductase gene
Appl. Biochem. Biotechnol.
97
135-145
2002
Mesocricetus auratus
brenda
Crane, Y.M.; Korth, K.L.
Regulated accumulation of 3-hydroxy-3-methylglutaryl CoA reductase protein in potato cell cultures: Effects of calcium and enzyme inhibitors
J. Plant Physiol.
159
1301-1307
2002
Solanum tuberosum
-
brenda
Hedl, M.; Rodwell, V.W.
Inhibition of the Class II HMG-CoA reductase of Pseudomonas mevalonii
Protein Sci.
13
1693-1697
2004
Pseudomonas mevalonii
brenda
Azenabor, A.A.; Kennedy, P.; Balistreri, S.
Chlamydia trachomatis Infection of Human Trophoblast Alters Estrogen and Progesterone Biosynthesis: an insight into role of infection in pregnancy sequelae
Int. J. Med. Sci.
4
223-231
2007
Homo sapiens
brenda
Shirai, N.; Suzuki, H.
Effect of docosahexaenoic acid on brain 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity in male ICR mice
J. Nutr. Biochem.
18
488-494
2007
Mus musculus
brenda
Kevei, Z.; Lougnon, G.; Mergaert, P.; Horvath, G.V.; Kereszt, A.; Jayaraman, D.; Zaman, N.; Marcel, F.; Regulski, K.; Kiss, G.B.; Kondorosi, A.; Endre, G.; Kondorosi, E.; Ane, J.
3-hydroxy-3-methylglutaryl coenzyme a reductase1 interacts with NORK and is crucial for nodulation in Medicago truncatula
Plant Cell
19
3974-3989
2007
Medicago truncatula
brenda
Perchellet, J.P.; Perchellet, E.M.; Crow, K.R.; Buszek, K.R.; Brown, N.; Ellappan, S.; Gao, G.; Luo, D.; Minatoya, M.; Lushington, G.H.
Novel synthetic inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity that inhibit tumor cell proliferation and are structurally unrelated to existing statins
Int. J. Mol. Med.
24
633-643
2009
Homo sapiens, Mus musculus
brenda
Yu, Q.; Liu, L.; Wang, Y.
Expression of low-density lipoprotein receptors and hydroxy methylglutaryl-coenzyme A-reductase in human pterygium
Int. J. Ophthal.
9
284-285
2009
Homo sapiens
-
brenda
Martini, C.; Trapani, L.; Narciso, L.; Marino, M.; Trentalance, A.; Pallottini, V.
3-Hydroxy 3-methylglutaryl coenzyme A reductase increase is essential for rat muscle differentiation
J. Cell. Physiol.
220
524-530
2009
Rattus norvegicus
brenda
Slotta, J.; Laschke, M.; Wang, Y.; Schilling, M.; Menger, M.; Thorlacius, H.
Inhibition of 3-hydroxy-3-methyl-glutaryl-coenzyme a reductase reduces leukocyte recruitment and hepatocyte apoptosis in endotoxin-induced liver injury
J. Investig. Med.
57
645-649
2009
Mus musculus
brenda
Ma, S.M.; Garcia, D.E.; Redding-Johanson, A.M.; Friedland, G.D.; Chan, R.; Batth, T.S.; Haliburton, J.R.; Chivian, D.; Keasling, J.D.; Petzold, C.J.; Lee, T.S.; Chhabra, S.R.
Optimization of a heterologous mevalonate pathway through the use of variant HMG-CoA reductases
Metab. Eng.
13
588-597
2011
Delftia acidovorans, Pseudomonas mevalonii, Bordetella petrii
brenda
Schwarz, B.H.; Driver, J.; Peacock, R.B.; Dembinski, H.E.; Corson, M.H.; Gordon, S.S.; Watson, J.M.
Kinetic characterization of an oxidative, cooperative HMG-CoA reductase from Burkholderia cenocepacia
Biochim. Biophys. Acta
1844
457-464
2014
Burkholderia cenocepacia (B4EKH5)
brenda
Ragwan, E.R.; Arai, E.; Kung, Y.
New Crystallographic snapshots of large domain movements in bacterial 3-hydroxy-3-methylglutaryl coenzyme A reductase
Biochemistry
57
5715-5725
2018
Delftia acidovorans
brenda
Peacock, R.B.; Hicks, C.W.; Walker, A.M.; Dewing, S.M.; Lewis, K.M.; Abboud, J.C.; Stewart, S.W.A.; Kang, C.; Watson, J.M.
Structural and functional characterization of dynamic oligomerization in Burkholderia cenocepacia HMG-CoA reductase
Biochemistry
58
3960-3970
2019
Burkholderia cenocepacia (B4EKH5), Burkholderia cenocepacia 32315 (B4EKH5)
brenda
Lammi, C.; Arnoldi, A.; Aiello, G.
Soybean peptides exert multifunctional bioactivity modulating 3-hydroxy-3-methylglutaryl-CoA reductase and dipeptidyl peptidase-IV targets in vitro
J. Agric. Food Chem.
67
4824-4830
2019
Homo sapiens
brenda
Li, T.; Liu, G.S.; Zhou, W.; Jiang, M.; Ren, Y.H.; Tao, X.Y.; Liu, M.; Zhao, M.; Wang, F.Q.; Gao, B.; Wei, D.Z.
Metabolic engineering of Saccharomyces cerevisiae to overproduce squalene
J. Agric. Food Chem.
68
2132-2138
2020
Ruegeria pomeroyi
brenda
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EXTERNAL LINKS (specific for EC-Number 1.1.1.88)
Transporter Classification Database (TCDB): 2.A.6.6.11
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