Information on EC 2.3.3.10 - hydroxymethylglutaryl-CoA synthase and Organism(s) Homo sapiens and UniProt Accession Q01581

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This record set is specific for:
Homo sapiens
UNIPROT: Q01581


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


The taxonomic range for the selected organisms is: Homo sapiens

EC NUMBER
COMMENTARY hide
2.3.3.10
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RECOMMENDED NAME
GeneOntology No.
hydroxymethylglutaryl-CoA synthase
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Acyl group transfer
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condensation
hydrolysis
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transacetylation
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
ferrichrome A biosynthesis
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isoprene biosynthesis II (engineered)
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ketogenesis
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mevalonate pathway I
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mevalonate pathway II (archaea)
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mevalonate pathway III (archaea)
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mevalonate metabolism
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Synthesis and degradation of ketone bodies
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Valine, leucine and isoleucine degradation
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Butanoate metabolism
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Terpenoid backbone biosynthesis
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Metabolic pathways
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Biosynthesis of secondary metabolites
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Biosynthesis of antibiotics
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SYSTEMATIC NAME
IUBMB Comments
acetyl-CoA:acetoacetyl-CoA C-acetyltransferase (thioester-hydrolysing, carboxymethyl-forming)
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CAS REGISTRY NUMBER
COMMENTARY hide
9027-44-5
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
acetyl-CoA + H2O + acetoacetyl-CoA
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
additional information
?
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
P54868, Q01581
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acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
acetyl-CoA + H2O + acetoacetyl-CoA
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
additional information
?
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the natural variant (V227A) of peroxisome proliferator-activated receptor-alpha (PPARalpha) significantly attenuates PPARalpha-mediated transactivation of the cytochrome P450 4A6 and mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2) genes in the presence of fibrate ligands
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(E,E)-11-[3-(hydroxymethyl)-4-oxo-2-oxytanyl]-3,5,7-trimethyl-2,4-undecadienenoic acid
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1-ethyl-3-(3-dimethylaminopropyl)carbodiimide
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2-benzyl-9-(3,6-dioxocyclohexa-1,4-dienyl)-2,3,7,8-tetrahydro-6H-pyrido[1,2-a]pyrazine-1,4-dione
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3-Chloropropionyl-CoA
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3-hydroxy-3-methylglutaryl-CoA
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acetoacetyl-CoA
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acetyloxy(phenyl)mercury
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phenyl mercuric acetate
diethylcarbamothioylsulfanyl N,N-diethylcarbamodithioate
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disulfiram
hymeglusin
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L-659,699
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potent inhibitor of the recombinant enzyme
Lifibrol
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.029 - 0.084
acetyl-CoA
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0011 - 0.0031
3-hydroxy-3-methylglutaryl-CoA
0.012
acetoacetyl-CoA
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0.0000537
L-659,699
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.76
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
8
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activity assay
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
24
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activity assay, A412 nm assay
30
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activity assay, A300 nm assay
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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enzyme is a direct target of c-Myc, which represses hydroxymethylglutaryl-CoA synthase transcriptional activity
Manually annotated by BRENDA team
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Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
UNIPROT
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
57290
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deduced amino acid sequence
120000
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gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
in complex with Co-A, sitting drop vapor diffusion method, using 0.1 M Bis-Tris (pH 6.5), 25% (w/v) polyethylene glycol (PEG) 3350, 0.2 M ammonium sulfate, at 4°C
in complex with (S)-3-hydroxy-3-methylglutaryl-CoA, sitting drop vapor diffusion method, using 0.2 M ammonium sulfate, 0.1 M Bis-Tris (pH 6.5), 25% (w/v) PEG 3350, at 20°C
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Ni-Sepharose resin column chromatography and Superdex 200 gel filtration
Ni-Sepharose resin column chromatography and Superdex 200 gel filtration
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli BL21(DE3) cells
cDNA cloned and sequenced
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cDNA subcloned and expressed from a T7-based vector in Escherichia coli
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expressed in Escherichia coli BL21(DE3) cells
expressed in Escherichia coli BL21-Codon Plus (DE3)-RIPL cells
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expression of recombinant wild-type cytoplasmic and Cys129 mutant enzymes
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into the vector pET-HSyn for expression in Escherichia coli cells
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
F174L
the mutant shows 10000fold decrease of activity compared to the wild type enzyme
G169D
the mutant is associated with HMGCS2 deficiency
G212R
inactive
G388R
the mutant is associated with HMGCS2 deficiency
I407T
the mutant is associated with HMGCS2 deficiency
I56N
the mutant is associated with HMGCS2 deficiency
K243E
the mutant is associated with HMGCS2 deficiency
L266S
the mutant is associated with HMGCS2 deficiency
M307T
the mutant is associated with HMGCS2 deficiency
R188H
the mutant is associated with HMGCS2 deficiency
R424X
the truncated mutant is nonfunctional
R500H
inactive
R505Q
the mutant is associated with HMGCS2 deficiency
T233A
the mutant is associated with HMGCS2 deficiency
V54M
the mutant is associated with HMGCS2 deficiency
Y167C
the mutant is associated with HMGCS2 deficiency
Y84X
the truncated mutant is nonfunctional
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
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a visible wavelength spectrophotometric assay suitable for high-throughput screening of 3-hydroxy-3-methylglutaryl-CoA synthase is established
medicine