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Information on EC 2.5.1.21 - squalene synthase and Organism(s) Homo sapiens

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EC Tree
IUBMB Comments
This microsomal enzyme catalyses the first committed step in the biosynthesis of sterols. The enzyme from yeast requires either Mg2+ or Mn2+ for activity. In the absence of NAD(P)H, presqualene diphosphate (PSPP) is accumulated. When NAD(P)H is present, presqualene diphosphate does not dissociate from the enzyme during the synthesis of squalene from farnesyl diphosphate (FPP) . High concentrations of FPP inhibit the production of squalene but not of PSPP .
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Homo sapiens
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
farnesyltransferase, squalene synthase, sqs, fdft1, squalene synthetase, farnesyl-diphosphate farnesyltransferase, sgsqs, ssase, sqase, tksqs1, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
farnesyl-diphosphate farnesyltransferase
-
-
-
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farnesyldiphosphate farnesyltransferase 1
-
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farnesyldiphosphate:farnesyldiphosphate farnesyltransferase
-
-
-
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farnesyltransferase
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-
-
-
FDFT1
-
-
presqualene synthase
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-
-
-
presqualene-diphosphate synthase
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-
-
-
squalene synthase
squalene synthetase
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-
-
-
SSase
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-
synthase, squalene
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-
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-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
2 (2E,6E)-farnesyl diphosphate + NAD(P)H + H+ = squalene + 2 diphosphate + NAD(P)+
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
alkenyl group transfer
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-
-
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reduction
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-
SYSTEMATIC NAME
IUBMB Comments
(2E,6E)-farnesyl-diphosphate:(2E,6E)-farnesyl-diphosphate farnesyltransferase
This microsomal enzyme catalyses the first committed step in the biosynthesis of sterols. The enzyme from yeast requires either Mg2+ or Mn2+ for activity. In the absence of NAD(P)H, presqualene diphosphate (PSPP) is accumulated. When NAD(P)H is present, presqualene diphosphate does not dissociate from the enzyme during the synthesis of squalene from farnesyl diphosphate (FPP) [8]. High concentrations of FPP inhibit the production of squalene but not of PSPP [8].
CAS REGISTRY NUMBER
COMMENTARY hide
9077-14-9
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2 (2E,6E)-farnesyl diphosphate
diphosphate + presqualene diphosphate
show the reaction diagram
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
show the reaction diagram
2 farnesyl diphosphate
presqualene diphosphate + diphosphate
show the reaction diagram
-
-
-
-
?
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
show the reaction diagram
farnesyl diphosphate + NAD(P)H + H+
squalene + diphosphate + NAD(P)+
show the reaction diagram
-
-
-
-
?
presqualene diphosphate + NAD(P)H + H+
squalene + diphosphate + NAD(P)+
show the reaction diagram
-
-
-
-
?
presqualene diphosphate + NADPH + H+
squalene + diphosphate + NADP+
show the reaction diagram
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
2 (2E,6E)-farnesyl diphosphate
diphosphate + presqualene diphosphate
show the reaction diagram
first half-reaction
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
show the reaction diagram
2 farnesyl diphosphate
presqualene diphosphate + diphosphate
show the reaction diagram
-
-
-
-
?
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
show the reaction diagram
-
enzyme may be important during response to infection and inflammation
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-
?
presqualene diphosphate + NAD(P)H + H+
squalene + diphosphate + NAD(P)+
show the reaction diagram
-
-
-
-
?
presqualene diphosphate + NADPH + H+
squalene + diphosphate + NADP+
show the reaction diagram
second half reaction
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-
?
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NAD(P)H
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NADH
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NADPH
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Mn2+
the enzyme requires either Mg2+ or Mn2+ as metal cofactor
additional information
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(1-[[(1R,5S)-7-chloro-5-(2-chlorophenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetyl]piperidin-4-yl)acetic acid
-
-
(1-[[(3R,5S)-1-[3-(acetyloxy)-2,2-dimethylpropyl]-7-chloro-5-(2,3-dimethoxyphenyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl]acetyl]piperidin-4-yl)acetic acid
-
i.e. lapaquistat acetate or TAK-475
(1-[[(3R,5S)-7-chloro-5-(2,3-dimethoxyphenyl)-1-(3-hydroxy-2,2-dimethylpropyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl]acetyl]piperidin-4-yl)acetic acid
-
-
(1-[[(6S)-8-chloro-6-(2,3-dimethoxyphenyl)-1-(propan-2-yl)-6,10b-dihydro-1H,4H-[2]benzoxepino[4,5-c][1,2]oxazol-4-yl]acetyl]piperidin-4-yl)acetic acid
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-
(1R,5S)-7-chloro-5-(2-methoxyphenyl)-1-(2-methylpropyl)-3-[2-oxo-2-(piperidin-1-yl)ethyl]-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one
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-
(2E)-3-[(1R,5S)-3-(carboxymethyl)-7-chloro-5-(2-chlorophenyl)-2-oxo-2,3,4,5-tetrahydro-1H-3-benzazepin-1-yl]-2-methylprop-2-enoic acid
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-
1-allyl-2-[3-(benzylamino)propoxy]-9H-carbazole
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50% inhibition at 63 nM
1-allyl-2-[3-(isopropylamino)propoxy]-9H-carbazole
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50% inhibition at 32 nM
1-allyl-2-[3-(isopropylamino)propoxy]-9H-xanthen-9-one
-
50% inhibition at 120 nM
1-[[(1R,5R)-7-chloro-5-(2,3-dimethoxyphenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetyl]piperidine-4-carboxylic acid
-
-
1-[[(1R,5S)-7-chloro-5-(2,3-dimethoxyphenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetyl]piperidine-4-carboxylic acid
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-
1-[[(1R,5S)-7-chloro-5-(2-chlorophenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetyl]piperidine-4-carboxylic acid
-
-
1-[[(1R,5S)-7-chloro-5-(2-methoxyphenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetyl]piperidine-4-carboxylic acid
-
-
1-[[(1S,5S)-7-chloro-5-(2,3-dimethoxyphenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetyl]piperidine-4-carboxylic acid
-
-
1-[[(6S)-8-chloro-6-(2,3-dimethoxyphenyl)-1-(propan-2-yl)-6,10b-dihydro-1H,4H-[2]benzoxepino[4,5-c][1,2]oxazol-4-yl]acetyl]piperidine-4-carboxylic acid
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-
2-[(6S)-8-chloro-6-(2,3-dimethoxyphenyl)-1-(propan-2-yl)-6,10b-dihydro-1H,4H-[2]benzoxepino[4,5-c][1,2]oxazol-4-yl]-1-[(3R)-3-hydroxypyrrolidin-1-yl]ethanone
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2-[3-(isopropylamino)propoxy]-9H-carbazole
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50% inhibition at 810 nM
3-(4-quinolin-6-ylphenyl)quinuclidin-3-ol
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i.e. RPR107393, 50% inhibition at 57 nM
3-C-carboxy-2,4-dideoxy-2-dodec-11-en-1-ylpentaric acid
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3-C-carboxy-2,4-dideoxy-2-dodecylpentaric acid
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6-([[(1R,5S)-7-chloro-5-(2-chlorophenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetyl]amino)hexanoic acid
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atorvastatin
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BMS 187745
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decrease of cholesterol or LDL
BMS-187745
-
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BMS-188494
BPH-701
about 60% inhibition at 0.005 mM
CHQHNSMYC
an ennea-peptide, slight inhibition
CKTE
a tetrapeptide
CKTENMQSC
an ennea-peptide
CLGV
a tetrapeptide
CLGVHSSSC
an ennea-peptide
CLSPHSMFC
an ennea-peptide
CP-294838
a benzoxazepinone IC50 130 nM
CP-295697
a bisphosphonate, IC50: 20 nM
CP-320473
-
CP-424677
-
CP-458003
-
CPWW
a tetrapeptide
CQMHQLSSC
an ennea-peptide
CSGMKTTGC
an ennea-peptide
CSTLKVATC
an ennea-peptide
CSTPWHQWC
an ennea-peptide
CTVNWYPLC
an ennea-peptide
cynarin
by the combination of three different computational approaches and biological assays, cynarin is selected as a potential squalene synthase inhibitor
EP2302
EP2306
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decrease of cholesterol or LDL
ER-27856
-
-
ethyl [(1R,5S)-7-chloro-5-(2-chlorophenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetate
-
-
KTTG
a tetrapeptide
lapaquistat
-
decrease of cholesterol or LDL
LSPH
a tetrapeptide
N-[[(3R,5S)-7-chloro-5-(2,3-dimethoxyphenyl)-1-(2,2-dimethylpropyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl]acetyl]-L-aspartic acid
-
-
RPR107393
-
-
simvastatin
-
-
SMFC
a tetrapeptide
SPHS
a tetrapeptide, slight inhibition
T-91485
-
-
TAK-475
WHQW
a tetrapeptide
YGPW
a tetrapeptide
zaragozic acid
zaragozic acid A
[(1R,5R)-7-chloro-1-(2-methylpropyl)-2-oxo-5-phenyl-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetic acid
-
-
[(1R,5S)-1-benzyl-7-chloro-5-(2-chlorophenyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetic acid
-
-
[(1R,5S)-5-(2-bromophenyl)-7-chloro-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetic acid
-
-
[(1R,5S)-5-(2-chlorophenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetic acid
-
-
[(1R,5S)-5-(2-chlorophenyl)-7-fluoro-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetic acid
-
-
[(1R,5S)-5-(2-chlorophenyl)-7-methyl-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetic acid
-
-
[(1R,5S)-7-chloro-5-(2,3-dimethoxyphenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetic acid
-
-
[(1R,5S)-7-chloro-5-(2-chlorophenyl)-1-(2-hydroxy-2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetic acid
-
-
[(1R,5S)-7-chloro-5-(2-chlorophenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetic acid
-
-
[(1R,5S)-7-chloro-5-(2-methoxyphenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetic acid
-
-
[(4R,6R)-8-chloro-6-(2,3-dimethoxyphenyl)-1-(propan-2-yl)-6,10b-dihydro-1H,4H-[2]benzoxepino[4,5-c][1,2]oxazol-4-yl]acetic acid
-
-
[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-1-(propan-2-yl)-6,10b-dihydro-1H,4H-[2]benzoxepino[4,5-c][1,2]oxazol-4-yl]acetic acid
-
-
[(4S,6R)-8-chloro-6-(2,3-dimethoxyphenyl)-1-(propan-2-yl)-6,10b-dihydro-1H,4H-[2]benzoxepino[4,5-c][1,2]oxazol-4-yl]acetic acid
-
-
[(4S,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-1-(propan-2-yl)-6,10b-dihydro-1H,4H-[2]benzoxepino[4,5-c][1,2]oxazol-4-yl]acetic acid
-
-
[(6S)-8-chloro-6-(2,3-dimethoxyphenyl)-1-(propan-2-yl)-6,10b-dihydro-1H,4H-[2]benzoxepino[4,5-c][1,2]oxazol-4-yl]acetic acid
-
-
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
-
overview on regulation
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0023
farnesyl diphosphate
-
additional information
additional information
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
510
(2E,6E)-farnesyl diphosphate
pH and temperature not specified in the publication, recombinant enzyme
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00000025
zaragozic acid
-
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0014
(1-[[(1R,5S)-7-chloro-5-(2-chlorophenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetyl]piperidin-4-yl)acetic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.000213
(1-[[(3R,5S)-1-[3-(acetyloxy)-2,2-dimethylpropyl]-7-chloro-5-(2,3-dimethoxyphenyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl]acetyl]piperidin-4-yl)acetic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.00026
(1-[[(3R,5S)-7-chloro-5-(2,3-dimethoxyphenyl)-1-(3-hydroxy-2,2-dimethylpropyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl]acetyl]piperidin-4-yl)acetic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.000131
(1-[[(6S)-8-chloro-6-(2,3-dimethoxyphenyl)-1-(propan-2-yl)-6,10b-dihydro-1H,4H-[2]benzoxepino[4,5-c][1,2]oxazol-4-yl]acetyl]piperidin-4-yl)acetic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.00037
(1R,5S)-7-chloro-5-(2-methoxyphenyl)-1-(2-methylpropyl)-3-[2-oxo-2-(piperidin-1-yl)ethyl]-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one
Homo sapiens
-
pH and temperature not specified in the publication
0.0055
(2E)-3-[(1R,5S)-3-(carboxymethyl)-7-chloro-5-(2-chlorophenyl)-2-oxo-2,3,4,5-tetrahydro-1H-3-benzazepin-1-yl]-2-methylprop-2-enoic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.00022
1-[[(1R,5R)-7-chloro-5-(2,3-dimethoxyphenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetyl]piperidine-4-carboxylic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.00045
1-[[(1R,5S)-7-chloro-5-(2,3-dimethoxyphenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetyl]piperidine-4-carboxylic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.00093
1-[[(1R,5S)-7-chloro-5-(2-chlorophenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetyl]piperidine-4-carboxylic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.0005
1-[[(1R,5S)-7-chloro-5-(2-methoxyphenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetyl]piperidine-4-carboxylic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.02
1-[[(1S,5S)-7-chloro-5-(2,3-dimethoxyphenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetyl]piperidine-4-carboxylic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.000112
1-[[(6S)-8-chloro-6-(2,3-dimethoxyphenyl)-1-(propan-2-yl)-6,10b-dihydro-1H,4H-[2]benzoxepino[4,5-c][1,2]oxazol-4-yl]acetyl]piperidine-4-carboxylic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.000162
2-[(6S)-8-chloro-6-(2,3-dimethoxyphenyl)-1-(propan-2-yl)-6,10b-dihydro-1H,4H-[2]benzoxepino[4,5-c][1,2]oxazol-4-yl]-1-[(3R)-3-hydroxypyrrolidin-1-yl]ethanone
Homo sapiens
-
pH and temperature not specified in the publication
0.0024
6-([[(1R,5S)-7-chloro-5-(2-chlorophenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetyl]amino)hexanoic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.087
CKTE
Homo sapiens
pH and temperature not specified in the publication
0.064
CLSPHSMFC
Homo sapiens
pH and temperature not specified in the publication
0.00013
CP-294838
Homo sapiens
a benzoxazepinone IC50 130 nM
0.00002
CP-295697
Homo sapiens
a bisphosphonate, IC50: 20 nM
0.02
ethyl [(1R,5S)-7-chloro-5-(2-chlorophenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetate
Homo sapiens
-
pH and temperature not specified in the publication
0.076
SMFC
Homo sapiens
pH and temperature not specified in the publication
0.09
WHQW
Homo sapiens
pH and temperature not specified in the publication
0.0000007
zaragozic acid
Homo sapiens
IC50 0.7 nM
0.0153
[(1R,5R)-7-chloro-1-(2-methylpropyl)-2-oxo-5-phenyl-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.02
[(1R,5S)-1-benzyl-7-chloro-5-(2-chlorophenyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.0022
[(1R,5S)-5-(2-bromophenyl)-7-chloro-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.02
[(1R,5S)-5-(2-chlorophenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.02
[(1R,5S)-5-(2-chlorophenyl)-7-fluoro-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.02
[(1R,5S)-5-(2-chlorophenyl)-7-methyl-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.0012
[(1R,5S)-7-chloro-5-(2,3-dimethoxyphenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.02
[(1R,5S)-7-chloro-5-(2-chlorophenyl)-1-(2-hydroxy-2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.0033
[(1R,5S)-7-chloro-5-(2-chlorophenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.0019
[(1R,5S)-7-chloro-5-(2-methoxyphenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.00142
[(4R,6R)-8-chloro-6-(2,3-dimethoxyphenyl)-1-(propan-2-yl)-6,10b-dihydro-1H,4H-[2]benzoxepino[4,5-c][1,2]oxazol-4-yl]acetic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.000056
[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-1-(propan-2-yl)-6,10b-dihydro-1H,4H-[2]benzoxepino[4,5-c][1,2]oxazol-4-yl]acetic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.000169
[(4S,6R)-8-chloro-6-(2,3-dimethoxyphenyl)-1-(propan-2-yl)-6,10b-dihydro-1H,4H-[2]benzoxepino[4,5-c][1,2]oxazol-4-yl]acetic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.0055
[(4S,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-1-(propan-2-yl)-6,10b-dihydro-1H,4H-[2]benzoxepino[4,5-c][1,2]oxazol-4-yl]acetic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.000223
[(6S)-8-chloro-6-(2,3-dimethoxyphenyl)-1-(propan-2-yl)-6,10b-dihydro-1H,4H-[2]benzoxepino[4,5-c][1,2]oxazol-4-yl]acetic acid
Homo sapiens
-
pH and temperature not specified in the publication
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
squalene synthase consists of both an N-terminal catalytic domain and a C-terminal domain tethering the enzyme to the endoplasmic reticulum membrane
Manually annotated by BRENDA team
bound, the membrane-binding domains of the human enzyme are 30 residues of the N-terminus and 47 residues of the C-terminus
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
physiological function
additional information
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
FDFT_HUMAN
417
0
48115
Swiss-Prot
other Location (Reliability: 1)
B4DND3_HUMAN
474
0
53405
TrEMBL
Mitochondrion (Reliability: 3)
B4DWP0_HUMAN
250
0
28529
TrEMBL
other Location (Reliability: 4)
Q6IAX1_HUMAN
417
0
48115
TrEMBL
other Location (Reliability: 1)
B4DTK0_HUMAN
174
0
20424
TrEMBL
Secretory Pathway (Reliability: 4)
A0A1W2PQ47_HUMAN
476
0
53629
TrEMBL
Mitochondrion (Reliability: 3)
B7Z9R8_HUMAN
353
0
40754
TrEMBL
Secretory Pathway (Reliability: 4)
E9PNM1_HUMAN
410
0
47285
TrEMBL
other Location (Reliability: 2)
PDB
SCOP
CATH
UNIPROT
ORGANISM
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
squalene synthase consists of both an N-terminal catalytic domain and a C-terminal domain tethering the enzyme to the endoplasmic reticulum membrane
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
in complex with different inhibitors
mutant with deletion of 47 C-terminal amino acids
purified recombinant truncated detagged SQS(31-370) in complex with inhibitor zaragozic acid A, vapour diffusion, mixing an equal volume of protein solution containing 15 mg/ml protein with precipitating solution containing 20% PEG2K-MME, 0.01 M NiCl2, 0.1 M Tris, pH 8.5, 1.4 M sodium citrate tribasic dehydrate, 0.1 M Na-HEPES, pH 7.5, 2 M K2HPO4/NaH2HPO4, pH 6.5, room temperature, X-ray diffraction structure determination and analysis, molecular replacement
-
purified recombinant wild-type and mutant enzymes in complex with Mg2+ and/or farnesyl diphosphate or presqualene diphosphate, respectively, mixing equal volumes of protein solution, containing 10 mg/ml protein and 3 mM substrate or 1 mM intermediate, with or without 1 mM Mg2+, with precipitant solution (form I: 20% PEG 2000 MME, 0.01 M NiCl2, 0.1 M Tris, pH 8.5 and form II: 1.4 M sodium citrate tribasic dehydrate, 0.1 M Na HEPES, pH 7.5; form III, 2 M K2HPO4/NaH2PO4, pH 6.5) at 25°C, X-ray diffraction structure determination and analysis at 1.75-2.35 A resolution, modelling
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
F288A
site-directed mutagenesis, structure comparison with bound metals and reaction intermediate PSPP compared to the wild-type enzyme
F288L
site-directed mutagenesis, structure comparison with bound metals and reaction intermediate PSPP compared to the wild-type enzyme
Q33R/D34N/S38N
the mutations do not affect the enzyme activity
Y73A
site-directed mutagenesis, structure comparison with bound metals and reaction intermediate PSPP compared to the wild-type enzyme
additional information
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli strain BL21 (DE3) by nickel affinity chromatography, the N-terminal His-tag is then cleaved using thrombin and removed using nickel affinity chromatography
recombinant protein
-
recombinant truncated N-terminally His6-tagged SQS(31-370) from Escherichia coli strain BL21(DE3), the tag is cleaved off by thrombin
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene FDFT1, quantitative reverse transcription-PCR enzyme expression analysis
gene fragment SQS(31-370) as N-terminally His6-tagged protein containing a thrombin cleavage site in Escherichia coli strain BL21(DE3)
-
gene hSQS, recombinant enzyme expression in Escherichia coli strain BL21 (DE3)
gene hsqs, recombinant expression of a truncated Q33R/D34N/S38N mutant lacking 30 N-terminal residues and 47 C-terminal residues in Escherichia coli strain XL1-Blue, coexpression with gene crtN encoding DSQ desaturase from Staphylococcus aureus in Escherichia coli results in carotinoid production and accumulation of C30 carotenoid pigments, which does not happen with coexpression of gene crtI encoding Pantoea ananatis phytoene desaturase, carotenoid pigment analysis, overview
gene hSQS, recombinant expression of His-tagged wild-type and mutant enzymes in Escherichia coli strain BL21 (DE3)
gene hsqs, recombinant functional expression of mutant enzyme with truncated membrane-binding domains, i.e. 30 residues of the N-terminus and 47 residues of the C-terminus, in Escherichia coli strain XL1-Blue, performance of the squalene hyperproducing strain is best at 37°C
gene SQS, recombinant enzyme expression in an enzyme-deficient SQS-knockout Saccharomyces cerevisiae DELTAerg9 strain, the enzyme can partially complement the knockout mutation when the gene is weakly expressed, but when highly expressed, the non-fungal squalene synthase cannot complement the yeast mutation and instead leads to the accumulation of a toxic intermediate(s) as defined by mutations of genes downstream in the ergosterol pathway
overview
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
drug development
industry
squalene has industrial value as a lubricant, health promoting agent, and/or drop-in biofuel, establishment of an efficient Escherichia coli-based system for squalene production
medicine
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Thompson, J.F.; Danley, D.E.; Mazzalupo, S.; Milos, P.M.; Lira, M.E.; Harwood, H.J., Jr.
Truncation of human squalene synthase yields active, crystallizable protein
Arch. Biochem. Biophys.
350
283-290
1998
Homo sapiens (P37268), Homo sapiens
Manually annotated by BRENDA team
Soltis, D.A.; McMahon, G.; Caplan, S.L.; Dudas, D.A.; Chamberlin, H.A.; Vattay, A.; Dottavio, D.; Rucker, M.L.; Engstrom, R.G.; et al.
Expression, purification, and characterization of the human squalene synthase: use of yeast and baculoviral systems
Arch. Biochem. Biophys.
316
713-723
1995
Homo sapiens
Manually annotated by BRENDA team
Tansey, T.R.; Shechter, I.
Structure and regulation of mammalian squalene synthase
Biochim. Biophys. Acta
1529
49-62
2000
Saccharomyces cerevisiae, Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Pandit, J.; Danley, D.E.; Schulte, G.K.; Mazzalupo, S.; Pauly, T.A.; Hayward, C.M.; Hamanaka, E.S.; Thompson, J.F.; Harwood, H.J., Jr.
Crystal structure of human squalene synthase. A key enzyme in cholesterol biosynthesis
J. Biol. Chem.
275
30610-30617
2000
Homo sapiens (P37268), Homo sapiens
Manually annotated by BRENDA team
Ishihara, T.; Kakuta, H.; Moritani, H.; Ugawa, T.; Yanagisawa, I.
Synthesis and biological evaluation of novel propylamine derivatives as orally active squalene synthase inhibitors
Bioorg. Med. Chem.
12
5899-5908
2004
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Charlton-Menys, V.; Durrington, P.N.
Squalene synthase inhibitors: clinical pharmacology and cholesterol-lowering potential
Drugs
67
11-16
2007
Homo sapiens
Manually annotated by BRENDA team
Brusselmans, K.; Timmermans, L.; Van de Sande, T.; Van Veldhoven, P.P.; Guan, G.; Shechter, I.; Claessens, F.; Verhoeven, G.; Swinnen, J.V.
Squalene synthase, a determinant of raft-associated cholesterol and modulator of cancer cell proliferation
J. Biol. Chem.
282
18777-18785
2007
Homo sapiens
Manually annotated by BRENDA team
Do, R.; Pare, G.; Montpetit, A.; Hudson, T.J.; Gaudet, D.; Engert, J.C.
K45R variant of squalene synthase increases total cholesterol levels in two study samples from a French Canadian population
Hum. Mutat.
29
689-694
2008
Homo sapiens
Manually annotated by BRENDA team
Seiki, S.; Frishman, W.H.
Pharmacologic inhibition of squalene synthase and other downstream enzymes of the cholesterol synthesis pathway: a new therapeutic approach to treatment of hypercholesterolemia
Cardiol. Rev.
17
70-76
2009
Canis lupus familiaris, Cavia porcellus, Cricetus cricetus, Oryctolagus cuniculus, Homo sapiens, Macaca sp., Callithrix sp., Mus musculus, Rattus norvegicus
Manually annotated by BRENDA team
Do, R.; Kiss, R.S.; Gaudet, D.; Engert, J.C.
Squalene synthase: a critical enzyme in the cholesterol biosynthesis pathway
Clin. Genet.
75
19-29
2009
Cavia porcellus, Oryctolagus cuniculus, Homo sapiens, Macaca mulatta, Mus musculus, Rattus norvegicus
Manually annotated by BRENDA team
Calo, F.; Bondke, A.; Richardson, J.; White, A.; Barrett, A.
Total synthesis and determination of the absolute stereochemistry of the squalene synthase inhibitors CJ-13,981 and CJ-13,982
Tetrahedron Lett.
50
3388-3390
2009
Homo sapiens
-
Manually annotated by BRENDA team
Griebenow, N.; Flessner, T.; Buchmueller, A.; Raabe, M.; Bischoff, H.; Kolkhof, P.
Identification and optimization of tetrahydro-2H-3-benzazepin-2-ones as squalene synthase inhibitors
Bioorg. Med. Chem. Lett.
21
2554-2558
2011
Homo sapiens
Manually annotated by BRENDA team
Griebenow, N.; Buchmueller, A.; Kolkhof, P.; Schamberger, J.; Bischoff, H.
Identification of 4H,6H-[2]benzoxepino[4,5-c][1,2]oxazoles as novel squalene synthase inhibitors
Bioorg. Med. Chem. Lett.
21
3648-3653
2011
Homo sapiens
Manually annotated by BRENDA team
Liu, C.I.; Jeng, W.Y.; Chang, W.J.; Ko, T.P.; Wang, A.H.
Binding modes of zaragozic acid A to human squalene synthase and staphylococcal dehydrosqualene synthase
J. Biol. Chem.
287
18750-18757
2012
Homo sapiens
Manually annotated by BRENDA team
Liu, C.I.; Jeng, W.Y.; Chang, W.J.; Shih, M.F.; Ko, T.P.; Wang, A.H.
Structural insights into the catalytic mechanism of human squalene synthase
Acta Crystallogr. Sect. D
70
231-241
2014
Homo sapiens (P37268), Homo sapiens
Manually annotated by BRENDA team
Shiuan, D.; Chen, Y.H.; Lin, H.K.; Huang, K.J.; Tai, D.F.; Chang, D.K.
Discovering peptide inhibitors of human squalene synthase through screening the phage-displayed cyclic peptide c7c library
Appl. Biochem. Biotechnol.
179
597-609
2016
Homo sapiens (P37268), Homo sapiens
Manually annotated by BRENDA team
Linscott, K.B.; Niehaus, T.D.; Zhuang, X.; Bell, S.A.; Chappell, J.
Mapping a kingdom-specific functional domain of squalene synthase
Biochim. Biophys. Acta
1861
1049-1057
2016
Arabidopsis thaliana, Homo sapiens (P37268), Saccharomyces cerevisiae (P53866), Saccharomyces cerevisiae, Botryococcus braunii (Q9SDW9)
Manually annotated by BRENDA team
Furubayashi, M.; Li, L.; Katabami, A.; Saito, K.; Umeno, D.
Directed evolution of squalene synthase for dehydrosqualene biosynthesis
FEBS Lett.
588
3375-3381
2014
Thermosynechococcus vestitus, Homo sapiens (P37268), Homo sapiens, Saccharomyces cerevisiae (P53866), Saccharomyces cerevisiae
Manually annotated by BRENDA team
Katabami, A.; Li, L.; Iwasaki, M.; Furubayashi, M.; Saito, K.; Umeno, D.
Production of squalene by squalene synthases and their truncated mutants in Escherichia coli
J. Biosci. Bioeng.
119
165-171
2015
Thermosynechococcus vestitus, Homo sapiens (P37268), Homo sapiens
Manually annotated by BRENDA team
Saito, K.; Shirasago, Y.; Suzuki, T.; Aizaki, H.; Hanada, K.; Wakita, T.; Nishijima, M.; Fukasawa, M.
Targeting cellular squalene synthase, an enzyme essential for cholesterol biosynthesis, is a potential antiviral strategy against hepatitis C virus
J. Virol.
89
2220-2232
2015
Homo sapiens (P37268), Homo sapiens
Manually annotated by BRENDA team
Chen, Y.; Chen, X.; Luo, G.; Zhang, X.; Lu, F.; Qiao, L.; He, W.; Li, G.; Zhang, Y.
Discovery of potential inhibitors of squalene synthase from traditional Chinese medicine based on virtual screening and in vitro evaluation of lipid-lowering effect
Molecules
23
1040
2018
Homo sapiens (P37268)
Manually annotated by BRENDA team