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Information on EC 1.1.1.88 - hydroxymethylglutaryl-CoA reductase and Organism(s) Pseudomonas mevalonii and UniProt Accession P13702

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Pseudomonas mevalonii
UNIPROT: P13702 not found.
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The taxonomic range for the selected organisms is: Pseudomonas mevalonii
The expected taxonomic range for this enzyme is: Bacteria, Archaea, Eukaryota
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
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
3-hydroxy-3-methylglutaryl coenzyme A reductase
-
-
-
-
beta-hydroxy-beta-methylglutaryl CoA-reductase
-
-
-
-
beta-hydroxy-beta-methylglutaryl coenzyme A reductase
-
-
-
-
HMG-CoA reductase
hydroxymethylglutaryl coenzyme A reductase
-
-
-
-
NADH-dependent HMG-CoA reductase
-
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
(R)-mevalonate + CoA + 2 NAD+ = 3-hydroxy-3-methylglutaryl-CoA + 2 NADH + 2 H+
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
redox reaction
-
-
-
-
oxidation
-
-
-
-
reduction
-
-
-
-
oxidative acylation
-
-
-
-
reductive deacylation
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
(R)-mevalonate:NAD+ oxidoreductase (CoA-acylating)
-
CAS REGISTRY NUMBER
COMMENTARY hide
37250-24-1
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(R)-mevalonate + CoA + 2 NAD+
(S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADH + 2 H+
show the reaction diagram
(R)-mevalonate + CoA + 2 NAD+
3-hydroxy-3-methylglutaryl-CoA + 2 NADH + 2 H+
show the reaction diagram
-
-
-
-
r
(R)-mevalonate + CoA + NADP+
3-hydroxy-3-methylglutaryl-CoA + NADPH + H+
show the reaction diagram
-
-
-
-
r
(S)-3-hydroxy-3-methylglutaryl-CoA + NADH + H+
(R)-mevalonate + NAD+ + CoA
show the reaction diagram
3-hydroxy-3-methylglutaryl-CoA + NADH + H+
mevalonate + CoA + NAD+
show the reaction diagram
DL-mevaldate + CoA + NAD+
3-hydroxy-3-methylglutaryl-CoA NADH + H+
show the reaction diagram
-
-
-
-
r
DL-mevaldate + CoA + NAD+
4-hydroxy-3-methylglutaryl-CoA NADH + H+
show the reaction diagram
-
-
-
-
r
DL-mevaldate + CoA + NAD+
5-hydroxy-3-methylglutaryl-CoA NADH + H+
show the reaction diagram
-
-
-
-
r
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
(R)-mevalonate + CoA + 2 NAD+
3-hydroxy-3-methylglutaryl-CoA + 2 NADH + 2 H+
show the reaction diagram
-
-
-
-
r
(S)-3-hydroxy-3-methylglutaryl-CoA + NADH + H+
(R)-mevalonate + NAD+ + CoA
show the reaction diagram
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NADH
reverse reaction
NADP+
-
NAD+ is 600000fold more efficient than NADP+ in wild-type enzyme
additional information
-
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
3-Hydroxy-3-methylbutyrate
-
-
3-hydroxy-3-methylcarboxylic acid
-
competitive inhibitor
3-hydroxy-3-methylglutarate
3-hydroxybutyrate
-
-
4-hydroxybutyrate
-
-
acetoacetate
beta-hydroxybutyrate
-
-
deoxycholate
-
competitive inhibitor
mevalonate
-
-
additional information
-
no inhibition citrate, succinate, glutarate, 3,3-dimethylacrylate, 2,2-dimethylpropionate, acetoacetate
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
CoA
-
mevaldehyde reduction
pantetheine
-
mevaldehyde reduction
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.27 - 3.7
(R,S)-mevalonate
0.039 - 0.1
CoA
0.03 - 0.5
CoASH
0.05 - 0.3
DL-3-hydroxy-3-methylglutaryl-CoA
0.61 - 36
DL-mevaldate
0.35
DL-mevalonate
-
oxidative acylation of mevalonate
0.22 - 0.3
mevalonate
0.06 - 1.23
NAD+
0.032 - 0.36
NADH
52
NADP+
-
wild-type enzyme, oxidative acylation of mevalonate
0.15
R-mevalonate
-
oxidative acylation of mevalonate
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
4.5
3-hydroxy-3-methylglutarate
-
standard conditions, inhibition by substrate analog
35
4-hydroxybutyrate
-
standard conditions, inhibition by substrate analog
3
acetoacetate
-
standard conditions, inhibition by substrate analog
0.8
beta-hydroxybutyrate
-
standard conditions, inhibition by substrate analog
0.28 - 35
lovastin
0.26
mevalonate
-
standard conditions, substrate inhibition
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.011
-
H381A-mutant, mevalonate acylation
0.029
-
H381N-mutant, mevalonate acylation
0.041
-
H381Q-mutant, mevalonate acylation
0.091
-
H381K-mutant, mevalonate acylation
0.163
-
mevalonate acylation
18
-
mevalonate acylation pH 8.1
2.7
-
reverse reaction, pH 7.9, 30°C
2.73
-
forward reaction, pH 7.9, 30°C
20.3
-
mevalonate acylation pH 11
54.2
-
cysteine-free mutant, mevalonate acylation
60.5
-
mevalonate acylation
65.6
-
C156A-mutant, mevalonate acylation
70.5
-
wild-type enzyme, mevalonate acylation
77.7
-
C296A-mutant, mevalonate acylation
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
10
-
H381A mutant, oxidative acylation of mevalonate
10.5
-
H381Q mutant, oxidative acylation of mevalonate
11
-
H381K mutant, oxidative acylation of mevalonate
6
-
oxidative acylation of mevalonate with NADP+ as cofactor
7.1
-
assay conditions
7.9
-
assay at, both reaction directions
8.1
-
oxidative acylation of mevalonate
9
-
oxidative acylation of mevalonate
9.2 - 9.6
-
oxidative acylation of mevalonate
9.5
-
H381N mutant, oxidative acylation of mevalonate
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
40
-
oxidative acylation of mevalonate
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
sequence comparisons of several species with class II and class I HMG-CoA reductases for analysis of cofactor binding, overview
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
MVAA_PSEMV
428
0
45590
Swiss-Prot
-
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
178000
-
gel filtration
270000
-
SDS-PAGE
270100
-
sedimentation equilibrium centrifugation
43000
-
alpha4, 4 * 43000, SDS-PAGE
45540
-
amino acid composition
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hexamer
-
3alpha2, XSA
tetramer
-
alpha4, 4 * 43000, SDS-PAGE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
3 A resolution, 3 dimers packed along three-fold crystallographic axis, hexamer
-
wild-type and mutants, H381A, H381N, H381K, H381Q, 3 A resolution
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C156/296 A
-
fully active, resistant to N-ethylmaleimide
C156A
-
fully active, resistant to N-ethylmaleimide
C296A
-
fully active
D146A
-
6670-fold more specific for NADP+ than wild-type
D146A/L148K
-
72200-fold more specific for NADP+ than wild-type
D146A/L148R
-
83300-fold more specific for NADP+ than wild-type
D146A/Q147K
-
no activity with NADP+ as cofactor
D146A/T192K
-
no activity with NADP+ as cofactor
D146A/T192R
-
no activity with NADP+ as cofactor
D146G
-
1170-fold more specific for NADP+ than wild-type
D146G/L148K
-
55600-fold more specific for NADP+ than wild-type
D146G/L148R
-
no activity with NADP+ as cofactor
D146G/T192K
-
3170-fold more specific for NADP+ than wild-type
D146G/T192R
-
4500-fold more specific for NADP+ than wild-type
D146N
-
no activity with NADP+ as cofactor
D146S
-
no activity with NADP+ as cofactor
H381A
-
6% of wild-type activity
H381K
H381N
H381Q
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
20 mM N-ethylmaleimide, 50 min, 12% activity
-
4-vinylpyridine, 20 min, 0°C, 76% activity
-
5,5'-dithiobis(2-nitrobenzoic acid), 20 min, 0°C, 20% activity
-
diethyl polycarbonate causes loss of activity
-
dithiothreitol causes loss of activity
-
EDTA causes loss of activity
-
N-ethylmaleimide, 20 min, 0°C, 0% activity
-
p-hydroxymercuribenzoate, 20 min, 0°C, 19% activity
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-180°C, 400 mM KCl, 12 months
-
-180°C, 400 mM KCl, 24 months
-
-20°C stable to repeated freezing and thawing
-
0°C, 10 hours, 5% loss of activity
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli
-
expressed in Escherichia coli BL21
-
expressed in Escherichia coli JM103
-
RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
after inactivation with diethyl polycarbonate addition of hydroxylamine restores 50% of activity
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
-
target enzyme for chemotherapy of hypercholesterolemias
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
-
Manually annotated by BRENDA team
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
Manually annotated by BRENDA team
Rodwell, V.W.; Bensch, W.R.
S-3-Hydroxy-3-methylglutaryl-CoA reductase from Pseudomonas
Methods Enzymol.
71
480-486
1981
Pseudomonas mevalonii
Manually annotated by BRENDA team
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
Manually annotated by BRENDA team
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
Manually annotated by BRENDA team
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
Manually annotated by BRENDA team
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
Manually annotated by BRENDA team
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
Manually annotated by BRENDA team
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
Manually annotated by BRENDA team
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
Manually annotated by BRENDA team
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
Manually annotated by BRENDA team
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)
Manually annotated by BRENDA team
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
Manually annotated by BRENDA team
Hedl, M.; Rodwell, V.W.
Inhibition of the Class II HMG-CoA reductase of Pseudomonas mevalonii
Protein Sci.
13
1693-1697
2004
Pseudomonas mevalonii
Manually annotated by BRENDA team
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
Bordetella petrii, Delftia acidovorans, Pseudomonas mevalonii
Manually annotated by BRENDA team