Information on EC 2.5.1.21 - squalene synthase

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

EC NUMBER
COMMENTARY
2.5.1.21
-
RECOMMENDED NAME
GeneOntology No.
squalene synthase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
2 (2E,6E)-farnesyl diphosphate + NAD(P)H + H+ = squalene + 2 diphosphate + NAD(P)+
show the reaction diagram
overall reaction
-
-
-
2 (2E,6E)-farnesyl diphosphate + NAD(P)H + H+ = squalene + 2 diphosphate + NAD(P)+
show the reaction diagram
mechanism
-
2 (2E,6E)-farnesyl diphosphate + NAD(P)H + H+ = squalene + 2 diphosphate + NAD(P)+
show the reaction diagram
enzyme also catalyses the reduction of presqualene diphosphate by NADPH to squalene
-
2 (2E,6E)-farnesyl diphosphate + NAD(P)H + H+ = squalene + 2 diphosphate + NAD(P)+
show the reaction diagram
enzyme also catalyses the reduction of presqualene diphosphate by NADPH to squalene; mechanism
-
2 (2E,6E)-farnesyl diphosphate + NAD(P)H + H+ = squalene + 2 diphosphate + NAD(P)+
show the reaction diagram
overview mechanism, kinetics
-
2 (2E,6E)-farnesyl diphosphate + NAD(P)H + H+ = squalene + 2 diphosphate + NAD(P)+
show the reaction diagram
mechanism
P37268
2 (2E,6E)-farnesyl diphosphate + NAD(P)H + H+ = squalene + 2 diphosphate + NAD(P)+
show the reaction diagram
enzyme also catalyses the reduction of presqualene diphosphate by NADPH to squalene
-
2 (2E,6E)-farnesyl diphosphate + NAD(P)H + H+ = squalene + 2 diphosphate + NAD(P)+
show the reaction diagram
enzyme also catalyses the reduction of presqualene diphosphate by NADPH to squalene
-
2 (2E,6E)-farnesyl diphosphate + NAD(P)H + H+ = squalene + 2 diphosphate + NAD(P)+
show the reaction diagram
overall reaction, reaction mechanism, overview
-
2 (2E,6E)-farnesyl diphosphate = diphosphate + presqualene diphosphate
show the reaction diagram
; 1a
-
-
-
presqualene diphosphate + NAD(P)H + H+ = squalene + diphosphate + NAD(P)+
show the reaction diagram
; 1b
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
alkenyl group transfer
-
-
-
-
reduction
-
-
PATHWAY
KEGG Link
MetaCyc Link
Biosynthesis of secondary metabolites
-
Metabolic pathways
-
Sesquiterpenoid and triterpenoid biosynthesis
-
Steroid biosynthesis
-
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].
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
farnesyl-diphosphate farnesyltransferase
-
-
-
-
farnesyl-diphosphate farnesyltransferase
-
-
farnesyl-diphosphate:farnesyldiphosphate farnesyltransferase
-
-
farnesyldiphosphate:farnesyldiphosphate farnesyltransferase
-
-
-
-
farnesyltransferase
-
-
-
-
presqualene synthase
-
-
-
-
presqualene-diphosphate synthase
-
-
-
-
SQS
I6Z427
gene name
SQS
H9L9T8
-
SQS1
Q9XJ31
-
SQS1
Solanum tuberosum Desiree
Q9XJ31
-
-
squalene synthase
-
-
-
-
squalene synthase
-
-
squalene synthase
-
-
squalene synthase
-
-
squalene synthase
-
-
squalene synthase
-
-
squalene synthase
-
-
squalene synthase
-
-
squalene synthase 1
Q9XJ31
-
squalene synthase 1
Solanum tuberosum Desiree
Q9XJ31
-
-
squalene synthetase
-
-
-
-
SSase
-
-
SSN
Leishmania donovani MHOM/IN/80/Dd8
Q257D4
-
-
synthase, squalene
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9077-14-9
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
isoform Sqs1. Sqs1 is the only functional squalene synthase in Arabidopsis thaliana. Isoform Sqs2 has no squalene synthase activity
UniProt
Manually annotated by BRENDA team
isoform Sqs2, lacking enzymatic activity due to the presence of an unusual Ser replacing the highly conserved Phe at position 287
UniProt
Manually annotated by BRENDA team
green microalga, race B
Q9M678
SwissProt
Manually annotated by BRENDA team
gene BfSS1
UniProt
Manually annotated by BRENDA team
licorice
-
-
Manually annotated by BRENDA team
a French Canadian population
-
-
Manually annotated by BRENDA team
recombinant enzyme
Uniprot
Manually annotated by BRENDA team
Leishmania donovani MHOM/IN/80/Dd8
-
UniProt
Manually annotated by BRENDA team
recombinant enzyme
-
-
Manually annotated by BRENDA team
overexpression in Eleutherococcus senticosus, results in enzyme activity up to 3fold higher than wild-type and increase in phytosterols beta-sitosterol and stigmasterol as well as in triterpene saponin levels
Uniprot
Manually annotated by BRENDA team
expressed in Escherichia coli
-
-
Manually annotated by BRENDA team
overexpressed in Escherichia coli
-
-
Manually annotated by BRENDA team
gene PSS1; clone 8380-1
UniProt
Manually annotated by BRENDA team
Solanum tuberosum Desiree
gene PSS1; clone 8380-1
UniProt
Manually annotated by BRENDA team
WsSQS; genes WsSQS1and WsSQS2
UniProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
-
Inhibition of squalene synthase leads directly to a reduction in cholesterol biosynthesis and thus to a fall in plasma cholesterol levels. Plasma LDL-cholesterol and triglycerides are lowered by squalene synthase inhibitors
malfunction
-
modifications in region IV prevents SQS from undergoing the second half-reaction, indicating that this region may reasonably constitute a functional NADPH binding site
metabolism
-
part of cholesterol biosynthesis pathway
metabolism
-
key enzyme in the isoprenoid pathway
metabolism
-
squalene synthase catalyzes the conversion of farnesyl pyrophosphate into squalene by reductive condensation. This is a crucial step in cholesterol biosynthesis, squalene serves as the exclusive precursor for cholesterol
metabolism
-
squalene synthase is a key enzyme involved in antifungal steroidal glycoalkaloids biosynthesis. Steroidal glycoalkaloids are a family of nitrogenous secondary metabolites acting as phytoalexins, e.g. gamma-solamargine and its aglycone solasodine from Solanum nigrum inhibiting hyphae formation of Fusarium oxysporum
metabolism
-, Q257D4
squalene synthase is a major enzyme in the sterol biosynthetic pathway
metabolism
-
squalene synthase catalyzes the committed step of sterol synthesis
metabolism
H9L9T8
squalene synthase is a key enzyme in the regulation of isoprenoid biosynthesis and is important in the withanolides biosynthesis pathway, overview
metabolism
-, I6Z427
squalene synthase is the key enzyme of saponin biosynthesis pathway
metabolism
-, Q32R64
squalene synthase catalyzes the first enzymatic step of the central isoprenoid pathway in sterol and triterpenoid biosynthesis
physiological function
-
influence on regulation of cholesterol metabolism
physiological function
-
essential role in embryonic development
physiological function
-, Q257D4
squalene synthase catalyses an unusual head-to-head reductive dimerization of two molecules of farnesyl-pyrophosphate in a two-step reaction to form squalene
physiological function
-, Q32R64
squalene synthase functions as a key regulator in channeling the carbon flux into both the primary and secondary metabolite branches, and squalene synthase may play a regulatory role in directing triterpene intermediates and sterol pathways
physiological function
Leishmania donovani MHOM/IN/80/Dd8
-
squalene synthase catalyses an unusual head-to-head reductive dimerization of two molecules of farnesyl-pyrophosphate in a two-step reaction to form squalene
-
metabolism
Leishmania donovani MHOM/IN/80/Dd8
-
squalene synthase is a major enzyme in the sterol biosynthetic pathway
-
additional information
-
enzyme overexpression leads a significant 4fold enhancement in squalene synthase activity and 2.5fold enhancement in withanolide A content, transformed cell suspension cultures also produce withaferin A, which is absent in the non-transformed cell cultures
additional information
H9L9T8
the catalytic site is composed of the large central cavity formed by antiparallel alpha helices with two aspartate rich regions (DXXXD) on opposite walls, these residues are considered to play roles in binding of prenyl phosphates by binding Mg2+ ions
additional information
-, I6Z427
the substrate binding site is present at the core region of the enzyme structure. The predicted active site involves Phe 204, Leu 205, Gln 206, Thr 208, Asn 209, Ala 293, and Leu 297. The aspartate side chains are involved in binding multiple Mg2+ ions that stabilize binding of diphosphate groups in the substrate.
additional information
-, Q32R64
methyl jasmonate, abscisic acid, and ethephon induce the accumulation of BfSS1 mRNA, overexpression of the BfSS1 gene in the sense orientation in Bupleurum falcatum increases the mRNA accumulation of downstream genes such as squalene epoxidase and cycloartenol synthase but decreases the mRNA levels of beta-amyrin synthase, a triterpene synthase mRNA. Methyljasmonate treatment of transgenic roots overexpressing BfSS1 in the sense orientation fails to stimulate beta-amyrin synthase mRNA accumulation but still enhances saikosaponin and phytosterol production
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(2E,6E)-3,7,10-trimethylundeca-2,6-dienyl diphosphate + NADPH
diphosphate + ?
show the reaction diagram
-
weak
-
-
?
(2E,6E)-3,7,11-trimethyldodeca-2,6-dienyl diphosphate + NADPH
diphosphate + ?
show the reaction diagram
-
-
-
-
?
(2E,6E)-3,7,12-trimethyltrideca-2,6-dienyl diphosphate + NADPH
diphosphate + ?
show the reaction diagram
-
weak
-
-
?
(2E,6E)-3,7-dimethyldodeca-2,6-dienyl diphosphate + NADPH
diphosphate + ?
show the reaction diagram
-
-
-
-
?
(2E,6E)-3,7-dimethyltetradeca-2,6-dienyl diphosphate + NADPH
diphosphate + ?
show the reaction diagram
-
weak
-
-
?
(2E,6E)-3,7-dimethyltrideca-2,6-dienyl diphosphate + NADPH
diphosphate + ?
show the reaction diagram
-
weak
-
-
?
(2E,6E)-3,7-dimethylundeca-2,6-dienyl diphosphate + NADPH
diphosphate + ?
show the reaction diagram
-
weak
-
-
?
(E,E)-7-desmethylfarnesyl diphosphate + NADPH
6,19-didesmethylsqualene + NADP+ + diphosphate
show the reaction diagram
-
at 60% of the efficiency that farnesyl diphosphate is converted to squalene
in absence of farnesyl diphosphate, 6-desmethylsqualene is produced in presence of farnesyl diphosphate
?
10,11-dihydrofarnesyl diphosphate + NADPH
2,3,22,23-tetrahydrosqualene + NADP+ + diphosphate
show the reaction diagram
-
at 60% of the efficiency that farnesyl diphosphate is converted to squalene
-
?
2 (2E,6E)-farnesyl diphosphate
diphosphate + presqualene diphosphate
show the reaction diagram
-
-
-
-
?
2 (2E,6E)-farnesyl diphosphate
diphosphate + presqualene diphosphate
show the reaction diagram
H9L9T8
-
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
show the reaction diagram
-
overall reaction
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
show the reaction diagram
Q9XJ31, -
overall reaction
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
show the reaction diagram
-, Q257D4
overall reaction
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
show the reaction diagram
H9L9T8
overall reaction
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
show the reaction diagram
Leishmania donovani MHOM/IN/80/Dd8
Q257D4
overall reaction
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
show the reaction diagram
Solanum tuberosum Desiree
Q9XJ31
overall reaction
-
-
?
2 farnesyl diphosphate
presqualene diphosphate + diphosphate
show the reaction diagram
-
-
-
-
?
2 farnesyl diphosphate
presqualene diphosphate + diphosphate
show the reaction diagram
B9WZW7, -
-
-
-
?
2 farnesyl diphosphate
presqualene diphosphate + diphosphate
show the reaction diagram
-
-
in absence of NADPH, formation of presqualene diphosphate
-
?
2 farnesyl diphosphate
presqualene diphosphate + diphosphate
show the reaction diagram
-
assay at pH 7.2, 30C, 3 h
-
-
?
2-methylfarnesyl diphosphate + NADPH
11-methylsqualene + NADP+ + diphosphate
show the reaction diagram
-
-
-
?
3-demethylfarnesyl diphosphate + NADPH
10-demethylsqualene + NADP+ + diphosphate
show the reaction diagram
-
-
-
?
farnesyl diphosphate
12,13-cis-dehydrosqualene + diphosphate
show the reaction diagram
-
-
-
?
farnesyl diphosphate
12,13-cis-dehydrosqualene + diphosphate
show the reaction diagram
-
in presence of Mn2+
12-cis-dehydrosqualene + diphosphate
?
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
show the reaction diagram
P37268
-
-
-
?
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
show the reaction diagram
-
-
-
-
?
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
show the reaction diagram
-
-
-
?
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
show the reaction diagram
-
-
-
?
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
show the reaction diagram
-
-
-
-
-
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
show the reaction diagram
-
-
-
?
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
show the reaction diagram
-
-
-
?
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
show the reaction diagram
-
-
-
?
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
show the reaction diagram
-
-
-
?
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
show the reaction diagram
-
-
-
?
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
show the reaction diagram
-
-
-
?
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
show the reaction diagram
-
-
-
?
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
show the reaction diagram
-
-
-
?
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
show the reaction diagram
-
first pathway-specific enzyme in cholesterol biosynthesis
-
-
-
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
show the reaction diagram
-
first pathway-specific enzyme in cholesterol biosynthesis
-
-
-
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
show the reaction diagram
-
squalene is the first sterol intermediate in cholesterol biosynthesis
-
-
-
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
show the reaction diagram
-
essential enzyme in cholesterol biosynthetic pathway
-
-
-
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
show the reaction diagram
-
enzyme may be important during response to infection and inflammation
-
-
-
farnesyl diphosphate + NAD(P)H
squalene + diphosphate + NAD(P)+
show the reaction diagram
-
-
-
?
farnesyl diphosphate + NAD(P)H
squalene + diphosphate + NAD(P)+
show the reaction diagram
-
-
-
?
farnesyl diphosphate + NAD(P)H
squalene + diphosphate + NAD(P)+
show the reaction diagram
-
-
-
?
farnesyl diphosphate + NAD(P)H
squalene + diphosphate + NAD(P)+
show the reaction diagram
-
-
-
?
farnesyl diphosphate + NAD(P)H
squalene + diphosphate + NAD(P)+
show the reaction diagram
-
-
-
?
farnesyl diphosphate + NAD(P)H
squalene + diphosphate + NAD(P)+
show the reaction diagram
-
-
-
?
farnesyl diphosphate + NAD(P)H
squalene + diphosphate + NAD(P)+
show the reaction diagram
-
-
-
?
farnesyl diphosphate + NAD(P)H
squalene + diphosphate + NAD(P)+
show the reaction diagram
-
-
-
?
farnesyl diphosphate + NAD(P)H
squalene + diphosphate + NAD(P)+
show the reaction diagram
-
-
-
?
farnesyl diphosphate + NAD(P)H
squalene + diphosphate + NAD(P)+
show the reaction diagram
-
-
-
?
farnesyl diphosphate + NAD(P)H
squalene + diphosphate + NAD(P)+
show the reaction diagram
-
-
-
?
farnesyl diphosphate + NAD(P)H
squalene + diphosphate + NAD(P)+
show the reaction diagram
-
-
-
?
farnesyl diphosphate + NAD(P)H
squalene + diphosphate + NAD(P)+
show the reaction diagram
-
-
-
?
farnesyl diphosphate + NAD(P)H
squalene + diphosphate + NAD(P)+
show the reaction diagram
-
-
presqualene diphosphate and squalene are produced in a ratio of 6:1
?
farnesyl diphosphate + NAD(P)H + H+
squalene + diphosphate + NAD(P)+
show the reaction diagram
-
-
-
-
?
farnesyl diphosphate + NAD(P)H + H+
squalene + diphosphate + NAD(P)+
show the reaction diagram
-
-
-
-
?
farnesyl diphosphate + NADPH + H+
squalene + diphosphate + NADP+
show the reaction diagram
-
-
sole product
-
?
geranylgeranyl diphosphate + geranylgeranyl diphosphate
prelycopersene diphosphate + diphosphate
show the reaction diagram
-
-
-
?
presqualene diphosphate + NAD(P)H
squalene + NAD(P)+ + diphosphate
show the reaction diagram
-
-
-
?
presqualene diphosphate + NAD(P)H
squalene + NAD(P)+ + diphosphate
show the reaction diagram
-
-
-
?
presqualene diphosphate + NAD(P)H
squalene + NAD(P)+ + diphosphate
show the reaction diagram
-
-
-
?
presqualene diphosphate + NAD(P)H
squalene + NAD(P)+ + diphosphate
show the reaction diagram
-
-
-
?
presqualene diphosphate + NAD(P)H
squalene + NAD(P)+ + diphosphate
show the reaction diagram
-
in presence of reducing pyridine nucleotide, preferably NADPH, squalene is formed, in absence of reducing cofactor the rate of the condensation reaction is lower and all of the product accumulates as presqualene diphosphate
-
-
?
presqualene diphosphate + NAD(P)H
squalene + NAD(P)+ + diphosphate
show the reaction diagram
-
in presence of reducing pyridine nucleotide, preferably NADPH, squalene is formed, in absence of reducing cofactor the rate of the condensation reaction is lower and all of the product accumulates as presqualene diphosphate
-
?
presqualene diphosphate + NAD(P)H
squalene + NAD(P)+ + diphosphate
show the reaction diagram
-
in presence of reducing pyridine nucleotide, preferably NADPH, squalene is formed, in absence of reducing cofactor the rate of the condensation reaction is lower and all of the product accumulates as presqualene diphosphate
-
?
presqualene diphosphate + NAD(P)H
squalene + NAD(P)+ + diphosphate
show the reaction diagram
-
in presence of reducing pyridine nucleotide, preferably NADPH, squalene is formed, in absence of reducing cofactor the rate of the condensation reaction is lower and all of the product accumulates as presqualene diphosphate
-
?
presqualene diphosphate + NAD(P)H
squalene + NAD(P)+ + diphosphate
show the reaction diagram
-
presqualene diphosphate synthetase and squalene synthetase are copurified during isolation
-
?
presqualene diphosphate + NAD(P)H
squalene + NAD(P)+ + diphosphate
show the reaction diagram
-
a single active site catalyzes both reactions
-
?
presqualene diphosphate + NAD(P)H
squalene + NAD(P)+ + diphosphate
show the reaction diagram
-
one protein with 2 catalytic sites may be involved in synthesis of presqualene diphosphate and for its reduction to squalene
-
-
?
presqualene diphosphate + NAD(P)H
squalene + NAD(P)+ + diphosphate
show the reaction diagram
-
the polymeric form of the enzyme also catalyzes the reduction of presqualene diphosphate by NADPH to squalene
-
-
?
presqualene 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
B9WZW7, -
-
-
-
?
presqualene diphosphate + NADPH + H+
squalene + diphosphate + NADP+
show the reaction diagram
-
-
-
-
?
presqualene diphosphate + NADPH + H+
squalene + diphosphate + NADP+
show the reaction diagram
-
-
-
-
?
presqualene diphosphate + NADPH + H+
squalene + diphosphate + NADP+
show the reaction diagram
H9L9T8
-
-
-
?
geranylgeranyl diphosphate + NAD(P)H
lycopersene + NAD(P)+ + diphosphate
show the reaction diagram
-
-
-
?
additional information
?
-
-
specificity overview
-
-
-
additional information
?
-
-
specificity overview
-
-
-
additional information
?
-
-
specificity overview
-
-
-
additional information
?
-
-
none of the following analogues gives nonpolar products: 7,11-dimethyl-3-ethyl-2,6,10-dodecatrienyl diphosphate, 6,7,10,11-tetrahydrofarnesyl diphosphate, 4-methylthiofarnesyl diphosphate, 4-fluorofarnesyl diphosphate
-
-
-
additional information
?
-
-
reaction is completely regioselective
-
-
-
additional information
?
-
-
replacement of 3-methyl of farnesyl diphosphate by an ethyl group or introduction of a methyl group at C-4 results in a complete loss of activity
-
-
-
additional information
?
-
-
no substrate: 6,7-dihydrofarnesyl diphosphate, 3-desmethylfarnesyl diphosphate, not metabolized: (E)-6,7,10,11-tetrahydrofarnesyl diphosphate
-
-
-
additional information
?
-
O48666, -
enzyme is key regulator not only for phytosterol but also for triterpene biosynthesis
-
-
-
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
2 (2E,6E)-farnesyl diphosphate
diphosphate + presqualene diphosphate
show the reaction diagram
H9L9T8
-
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
show the reaction diagram
Q9XJ31, -
overall reaction
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
show the reaction diagram
-, Q257D4
overall reaction
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
show the reaction diagram
H9L9T8
overall reaction
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
show the reaction diagram
Leishmania donovani MHOM/IN/80/Dd8
Q257D4
overall reaction
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
show the reaction diagram
Solanum tuberosum Desiree
Q9XJ31
overall reaction
-
-
?
2 farnesyl diphosphate
presqualene diphosphate + diphosphate
show the reaction diagram
-
-
-
-
?
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
show the reaction diagram
-
-
-
-
-
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
show the reaction diagram
-
first pathway-specific enzyme in cholesterol biosynthesis
-
-
-
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
show the reaction diagram
-
first pathway-specific enzyme in cholesterol biosynthesis
-
-
-
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
show the reaction diagram
-
squalene is the first sterol intermediate in cholesterol biosynthesis
-
-
-
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
show the reaction diagram
-
essential enzyme in cholesterol biosynthetic pathway
-
-
-
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
-
-
-
-
?
presqualene diphosphate + NADPH + H+
squalene + diphosphate + NADP+
show the reaction diagram
H9L9T8
-
-
-
?
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
show the reaction diagram
-
enzyme may be important during response to infection and inflammation
-
-
-
additional information
?
-
O48666, -
enzyme is key regulator not only for phytosterol but also for triterpene biosynthesis
-
-
-
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
NAD(P)H
-, Q257D4
-
NADH
-
NADH or NADPH required for squalene synthase reaction
NADH
-
preference for NADPH over NADH
NADH
-
preference for NADPH over NADH
NADPH
-
NADPH or NADH required for squalene synthase reaction
NADPH
-
preference for NADPH over NADH
NADPH
-
preference for NADPH over NADH
NADPH
-
region IV of SQS may constitute a functional NADPH binding site
NADPH
Q9XJ31, -
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Mg2+
-
required for squalene synthase reaction
Mg2+
-
Mn2+ is more effective than Mg2+ in activation of dehydrosqualene formation; most effective in stimulation of squalene formation, half-maximal activity at 2.5 mM
Mg2+
-
Mn2+ is six times more effective in activation than Mg2+
Mg2+
-
no effect
Mg2+
-
Mn2+ is more effective than Mg2+ in activation of dehydrosqualene formation; required for squalene synthase reaction
Mg2+
-
Mn2+ or Mg2+ are effective at low concentration as cofactors for synthesis of lycopersene, for the synthesis of prelycopersene diphosphate, Mn2+ is most effective at very low concentrations, Mg2+ is more effective at higher concentrations
Mg2+
-
required, best at 10 mM, inhibition above 35 mM
Mg2+
-
cofactor
Mg2+
-, Q257D4
required
Mg2+
H9L9T8
required, the catalytic site is composed of the large central cavity formed by antiparallel alpha helices with two aspartate rich regions (DXXXD) on opposite walls, these residues are considered to play roles in binding of prenyl phosphates by binding Mg2+ ions
Mg2+
-, I6Z427
the aspartate side chains are involved in binding multiple Mg2? ions that stabilize binding of diphosphate groups in the substrate
Mn2+
-
more effective than Mg2+ in activation of dehydrosqualene formation
Mn2+
-
in presence of Mn2+ and Mg2+ the activity is reduced to one-third of that in presence of Mn2+ alone; six times more effective in activation than Mg2+
Mn2+
-
in presence of Mn2+ and Mg2+ the activity is reduced to one-third of that in presence of Mn2+ alone; stimulation
Mn2+
-
more effective than Mg2+ in activation of dehydrosqualene formation; stimulates, maximum stimulation at 0.1 mM
Mn2+
-
Mn2+ or Mg2+ are effective at low concentration as cofactors for synthesis of lycopersene, for the synthesis of prelycopersene diphosphate, Mn2+ is most effective at very low concentrations, Mg2+ is more effective at higher concentrations
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
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)-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
-
-
(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
-
-
(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
-
-
(3R)-3-[[3-(benzyloxy)phenyl]ethynyl]-1-azabicyclo[2.2.2]octan-3-ol
-
IC50: 1500 nM
(3S)-1-(3-((4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl)propanoyl)-3-piperidine carboxylic acid
-
-
(3S)-1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetyl]-3-piperidinecarboxylic acid
-
-
1,3-diallyl-2-[3-(isopropylamino)propoxy]-9H-carbazole
-
50% inhibition at 250 nM
1-(2-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-2H-1,2,3,4-tetrazol-5-yl)cyclopropanecarboxylic acid
-
-
1-(3-((4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl)propanoyl)-3-azetidine carboxylic acid
-
-
1-allyl-2-(3-anilinopropoxy)-9H-carbazole
-
50% inhibition at above 0.001 mM nM
1-allyl-2-[3-(benzylamino)propoxy]-9H-carbazole
-
50% inhibition at 63 nM
1-allyl-2-[3-(benzylamino)propoxy]-9H-carbazole hydrochloride
-
50% inhibition at 150 nM
1-allyl-2-[3-(cyclohexylamino)propoxy]-9H-carbazole
-
50% inhibition at 310 nM
1-allyl-2-[3-(cyclopropylamino)propoxy]-9H-carbazole
-
50% inhibition at 230 nM
1-allyl-2-[3-(isobutylamino)propoxy]-9H-carbazole
-
50% inhibition at 400 nM
1-allyl-2-[3-(isopropylamino)propoxy]-9H-carbazole
-
50% inhibition at 32 nM
1-allyl-2-[3-(isopropylamino)propoxy]-9H-carbazole
-
50% inhibition at 66 nM
1-allyl-2-[3-(isopropylamino)propoxy]-9H-xanthen-9-one
-
50% inhibition at 120 nM
1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetyl]-4-piperidinecarboxylic acid
-
-
1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-1H-1,2,3-triazole-4-carboxylic acid
-
-
1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-1H-pyrazole-4-carboxylic acid
-
-
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
-
-
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
-
-
2-(1-(3-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]propanoyl)-3-azetidinyl)acetic acid
-
-
2-(1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetyl]-4-piperidinyl)acetic acid
-
-
-
2-(1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-1H-1,2,3-triazol-4-yl)acetic acid
-
-
2-(1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-1H-1,2,3-triazol-5-yl)acetic acid
-
-
2-(1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-1H-pyrazol-3-yl)acetic acid
-
-
2-(1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-1H-pyrazol-4-yl)acetic acid
-
-
2-(1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-1H-pyrazol-5-yl)acetic acid
-
-
2-(1-[2-[(4S,6R)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetyl]-4-piperidinyl)acetic acid
-
-
2-(1-[2-[8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetyl]-4-piperidinyl)acetic acid
-
-
2-(1-[3-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]propanoyl]-4-piperidinyl)acetic acid
-
-
2-(2-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl)ethyl]-2H-1,2,3,4-tetrazol-5-yl]-2-methylpropanoic acid
-
-
2-(2-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl)ethyl]-2H-1,2,3,4-tetrazol-5-yl]acetic acid
-
-
2-(2-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-1H-1,2,3,4-tetrazol-5-yl)acetic acid
-
-
2-(4-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetyl]-1-piperazinyl)acetic acid
-
-
2-(4-[3-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]propanoyl]-2-oxo-1-piperazinyl)acetic acid
-
-
2-([2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetyl]amino)acetic acid
-
-
2-[(1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-1H-1,2,3-triazol-4-yl)methoxy]-2-ethylbutanoic acid
-
-
2-[(1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-1H-1,2,3-triazol-4-yl)methoxy]-2-methylpropanoic acid
-
-
2-[(1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-1H-1,2,3-triazol-4-yl)methoxy]acetic acid
-
-
2-[(1-[3-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]propanoyl]-4-piperidinyl)methoxy]acetic acid
-
-
2-[(1-[3-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]propanoyl]-4-piperidinyl)oxy]acetic acid
-
-
2-[(2-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-2H-1,2,3,4-tetrazol-5-yl)methoxy]-2-methylpropanoic acid
-
-
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
-
-
2-[1,8-dichloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetic acid
-
-
2-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-2H-1,2,3,4-tetrazol-5-carboxylic acid
-
-
2-[3-(isopropylamino)propoxy]-1-ethyl-9H-carbazole
-
50% inhibition at 460 nM
2-[3-(isopropylamino)propoxy]-9H-carbazole
-
50% inhibition at 810 nM
2-[3-(isopropylamino)propoxy]-9H-carbazole
-
50% inhibition at 110 nM
2-[8-chloro-6-(1-naphthyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetic acid
-
-
2-[8-chloro-6-(2,3-dichlorobenzoyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetic acid
-
-
2-[8-chloro-6-(2,3-dihydro-1,4-benzodioxin-5-yl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetic acid
-
-
2-[8-chloro-6-(2,3-dimethoxyphenyl)-1-(4-morpholinylmethyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetic acid
-
-
2-[8-chloro-6-(2,3-dimethoxyphenyl)-1-[(dimethylamino)methyl]-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetic acid
-
-
2-[8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetic acid
-
-
2-[[(2Z)-2-(1-azabicyclo(2.2.2)oct-3-ylidene)-2-fluoroethyl]oxy]-9H-carbazole
-
i.e. YM-53601, 50% inhibition at 90 nM
3-(2-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-2H-1,2,3,4-tetrazol-5-yl)propanoic acid
-
-
3-(4-quinolin-6-ylphenyl)quinuclidin-3-ol
-
i.e. RPR107393, 50% inhibition at 57 nM
3-(4-quinolin-6-ylphenyl)quinuclidin-3-ol
-
i.e. RPR107393, 50% inhibition at 68 nM
3-(biphenyl-4-yl)-2,3-dehydroquinuclidine
-
50% inhibition at 243 nM
3-(biphenyl-4-yl)-3-hydroxyquinuclidine
-
50% inhibition at 13 nM
3-(biphenyl-4-yl)-4'[(t-butyldimethylsilyl)oxy]-3-hydroxyquinuclidine
-
50% inhibition above 0.001 mM
3-(biphenyl-4-yl-4'-hydroxy)-2,3-dehydroquinuclidine
-
50% inhibition at 96 nM
3-(biphenyl-4-ylmethyl)-1-azabicyclo[2.2.2]oct-2-ene
-
IC50: 730 nM
3-([2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetyl]amino)benzoic acid
-
-
3-([2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetyl]amino)propionic acid
-
-
3-C-carboxy-2,4-dideoxy-2-dodec-11-en-1-ylpentaric acid
-
-
3-C-carboxy-2,4-dideoxy-2-dodecylpentaric acid
-
-
3-[(1-[3-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]propanoyl]-4-piperidinyl)oxy]propanoic acid
-
-
3-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6Hpyrrolo[1,2-a][4,1]benzoxazepin-4-yl]propionic acid
-
-
3-[[4-(benzyloxy)phenyl]ethynyl]-1-azabicyclo[2.2.2]oct-2-ene
-
IC50: 830 nM
4-[3-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]propanoyl]-2-morpholine carboxylic acid
-
-
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
-
-
Ammonium analogues
-
overview
-
atorvastatin
-
-
BMS 187745
-
decrease of cholesterol or LDL
BMS-187745
-
-
BMS-188494
-
decrease of cholesterol or LDL
BMS-188494
-
no induction of myotoxicity
chlorogenic acid
-
-
CP-294838
P37268
a benzoxazepinone IC50 130 nM
CP-295697
P37268
a bisphosphonate, IC50: 20 nM
E5700
-
IC50: 0.84 nM
EP2302
-
decrease of cholesterol or LDL
EP2302
-
decrease of cholesterol and triglyceride biosynthesis
EP2306
-
decrease of cholesterol or LDL
EP2306
-
decrease of cholesterol and triglyceride biosynthesis
ER-27856
-
decrease of cholesterol biosynthesis
ER-28448
-
decrease of cholesterol biosynthesis
ER119884
-
IC50: 3.52 nM
ethyl 4-(1-azabicyclo[2.2.2]oct-2-en-3-yl)benzoate
-
IC50: 50 nM
ethyl [(1R,5S)-7-chloro-5-(2-chlorophenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetate
-
-
farnesyl diphosphate
-
no inhibition of presqualene diphosphate synthase reaction; substrate inhibitor of squalene synthase reaction
farnesyl diphosphate
-
substrate inhibitor of squalene synthase reaction
Guanidinium chloride
-, Q257D4
loss of 86% activity at 0.3M GdmCl, 50% at 0.2 M
lapaquistat
-
lipid-lowering effect
lapaquistat
-
decrease of cholesterol or LDL
lapaquistat
-
lipid-lowering effect
methyl 2-[8-chloro-6-(2,3-dimethoxyphenyl)-4H,6Hpyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetate
-
-
N-isopropyl-biphenyloxypropylamine
-
50% inhibition at 93 nM
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
-
-
NADP+
-
inhibitor of squalene synthesis
RPR107393
-
reduction in plasma cholesterol concentrations
RPR107393
-
reduction of plasman cholesterol concentrations
RPR107393
-
-
RPR107393
-
inhibition of cholesterol biosynthesis and reduced plasma total cholesterol levels
simvastatin
-
-
squalestatin
-
hypolipidemic effects but potential toxicity because of high levels of urinary dicarboxylic acid
Urea
-, Q257D4
loss of 81% activity at 2 M, 50% at 1 M
YM-53601
-
decrease of non-high-density lipoprotein cholesterol
YM-53601
-
reduction of non-high-density lipoprotein cholesterol concentrations
zaragozic acid
P37268
IC50 0.7 nM
-
zaragozic acid
-
competitive to farnesyl diphosphate
-
zaragozic acid
-
hypolipidemic effects but potential toxicity because of high levels of urinary dicarboxylic acid
-
zaragozic acid
-
-
-
zaragozic acid
-
decrease in plasma cholesterol
-
zaragozic acid A
-
0.04 mM
zaragozic acid A
-
inhibition of squalene synthase. Administration also significantly increases the rate of degradation of hepatic low density lipoprotein receptor protein, and increases proprotein convertase subtilisin/kexin type 9 mRNA and protein levels in concert with an increase in hepatic low density lipoprotein receptor mRNA levels, low density lipoprotein turnover, and decreases in serum cholesterol levels
zaragozic acid A
-
pH 7.2, 37C
zaragozic acid A
-, Q257D4
is a potent inhibitor of mammalian SSN and also a competitive inhibitor of recombinant Leishmania donovani SSN, 50% inhibition at 100 nM
zaragozic acid A
-
enzyme binding induces a local conformational change in the substrate binding site, and its C-6 acyl group also extends over to the cofactor binding cavity, enzyme-inhibitor binding structure and thermodynamics, detailed overview
[(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
-
peroxisomal squalene synthase is inhibited by sonication, microsomal enzyme not
-
additional information
-
identification and optimization of tetrahydro-2H-3-benzazepin-2-ones as squalene synthase inhibitors, overview
-
additional information
-
4H,6H-[2]benzoxepino[4,5-c][1,2]oxazoles as squalene synthase inhibitors, design, synthesis, structure-activity relationship, and pharmacological profiles, overview
-
additional information
-
design, synthesis, and identification of highly potent benzhydrol derivatives as squalene synthase inhibitors, design of tricyclic pyrrolobenzoxazepine derivatives, overview
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
NADPH
-
stimulates
NADPH
-
maximal activity at 2 mM
Tween 20
-
stimulates recombinant enzyme
Tween 40
-
stimulates recombinant enzyme
Tween 80
-
stimulates recombinant enzyme
Tween 80
-
maximal activity at 2% v/v
W-1
-
detergent, stimulates recombinant enzyme
-
Bovine serum albumin
-
activates recombinant enzyme
-
additional information
-
absolute requirement for phospholipid
-
additional information
-
overview on regulation
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0038
-
(2E,6E)-farnesyl diphosphate
-, Q257D4
pH 7.4, 37C
0.0004
-
farnesyl diphosphate
-
cosubstrate NADPH
0.00097
-
farnesyl diphosphate
-
pH 7.2, 37C
0.0023
-
farnesyl diphosphate
P37268
-
0.0025
-
farnesyl diphosphate
-
-
0.00525
-
farnesyl diphosphate
-
in 50 mM morpholinepropanesulfonic acid-NaOH buffer (pH 7.4), 20 mM MgCl2, 5 mM 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate, 1% Tween 80, 10 mM dithiothreitol, 0.025 mg/ml bovine serum albumin, 0.25 mM NADPH, at 37C
0.0078
-
farnesyl diphosphate
-
-
0.02334
-
NADPH
-
in 50 mM morpholinepropanesulfonic acid-NaOH buffer (pH 7.4), 20 mM MgCl2, 5 mM 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate, 1% Tween 80, 10 mM dithiothreitol, 0.025 mg/ml bovine serum albumin, 0.25 mM NADPH, at 37C
0.04323
-
NADPH
-, Q257D4
pH 7.4, 37C
0.001
-
trans-farnesyl diphosphate
-
cosubstrate NADPH
0.0095
-
farnesyl diphosphate
-
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-, Q257D4
kinetics, recombinant LdSSN, overview
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.53
-
farnesyl diphosphate
-
cosubstrate + NAD(P)H
1.74
-
farnesyl diphosphate
-
-
3.3
-
farnesyl diphosphate
-
in presence of 1% Tween 80 and Mg2+
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
2.5e-07
-
zaragozic acid
-
-
-
7.4e-05
-
zaragozic acid A
-, Q257D4
pH 7.4, 37C
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
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
-
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
-
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
-
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
-
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
-
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
-
pH and temperature not specified in the publication
0.0015
-
(3R)-3-[[3-(benzyloxy)phenyl]ethynyl]-1-azabicyclo[2.2.2]octan-3-ol
-
IC50: 1500 nM
1.4e-06
-
(3S)-1-(3-((4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl)propanoyl)-3-piperidine carboxylic acid
-
pH 7.2-7.5, 37C
2.3e-06
-
(3S)-1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetyl]-3-piperidinecarboxylic acid
-
pH 7.2-7.5, 37C
1.7e-06
-
1-(2-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-2H-1,2,3,4-tetrazol-5-yl)cyclopropanecarboxylic acid
-
pH 7.2-7.5, 37C
2.2e-06
-
1-(3-((4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl)propanoyl)-3-azetidine carboxylic acid
-
pH 7.2-7.5, 37C
3.4e-06
-
1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetyl]-4-piperidinecarboxylic acid
-
pH 7.2-7.5, 37C
5.9e-07
-
1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-1H-1,2,3-triazole-4-carboxylic acid
-
pH 7.2-7.5, 37C
2.1e-06
-
1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-1H-pyrazole-4-carboxylic acid
-
pH 7.2-7.5, 37C
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
-
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
-
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
-
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
-
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
-
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
-
pH and temperature not specified in the publication
7e-06
-
2-(1-(3-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]propanoyl)-3-azetidinyl)acetic acid
-
pH 7.2-7.5, 37C
1.3e-06
-
2-(1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetyl]-4-piperidinyl)acetic acid
-
pH 7.2-7.5, 37C
-
5.1e-07
-
2-(1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-1H-1,2,3-triazol-4-yl)acetic acid
-
pH 7.2-7.5, 37C
8.1e-07
-
2-(1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-1H-1,2,3-triazol-5-yl)acetic acid
-
pH 7.2-7.5, 37C
1.3e-06
-
2-(1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-1H-pyrazol-3-yl)acetic acid
-
pH 7.2-7.5, 37C
3.1e-06
-
2-(1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-1H-pyrazol-4-yl)acetic acid
-
pH 7.2-7.5, 37C
1.6e-06
-
2-(1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-1H-pyrazol-5-yl)acetic acid
-
pH 7.2-7.5, 37C
0.0006
-
2-(1-[2-[(4S,6R)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetyl]-4-piperidinyl)acetic acid
-
pH 7.2-7.5, 37C
2.7e-06
-
2-(1-[2-[8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetyl]-4-piperidinyl)acetic acid
-
pH 7.2-7.5, 37C
2.4e-06
-
2-(1-[3-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]propanoyl]-4-piperidinyl)acetic acid
-
pH 7.2-7.5, 37C
1.1e-06
-
2-(2-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl)ethyl]-2H-1,2,3,4-tetrazol-5-yl]-2-methylpropanoic acid
-
pH 7.2-7.5, 37C
1.1e-06
-
2-(2-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl)ethyl]-2H-1,2,3,4-tetrazol-5-yl]acetic acid
-
pH 7.2-7.5, 37C
1.1e-06
-
2-(2-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-1H-1,2,3,4-tetrazol-5-yl)acetic acid
-
pH 7.2-7.5, 37C
4.3e-06
-
2-(4-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetyl]-1-piperazinyl)acetic acid
-
pH 7.2-7.5, 37C
2.2e-06
-
2-(4-[3-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]propanoyl]-2-oxo-1-piperazinyl)acetic acid
-
pH 7.2-7.5, 37C
2.3e-06
-
2-([2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetyl]amino)acetic acid
-
pH 7.2-7.5, 37C
1.7e-06
-
2-[(1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-1H-1,2,3-triazol-4-yl)methoxy]-2-ethylbutanoic acid
-
pH 7.2-7.5, 37C
6.9e-07
-
2-[(1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-1H-1,2,3-triazol-4-yl)methoxy]-2-methylpropanoic acid
-
pH 7.2-7.5, 37C
6.8e-07
-
2-[(1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-1H-1,2,3-triazol-4-yl)methoxy]acetic acid
-
pH 7.2-7.5, 37C
9e-07
-
2-[(1-[3-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]propanoyl]-4-piperidinyl)methoxy]acetic acid
-
pH 7.2-7.5, 37C
8e-07
-
2-[(1-[3-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]propanoyl]-4-piperidinyl)oxy]acetic acid
-
pH 7.2-7.5, 37C
2.5e-06
-
2-[(2-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-2H-1,2,3,4-tetrazol-5-yl)methoxy]-2-methylpropanoic acid
-
pH 7.2-7.5, 37C
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
-
pH and temperature not specified in the publication
1.6e-06
-
2-[1,8-dichloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetic acid
-
pH 7.2-7.5, 37C
8.9e-07
-
2-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-2H-1,2,3,4-tetrazol-5-carboxylic acid
-
pH 7.2-7.5, 37C
0.0006
-
2-[8-chloro-6-(1-naphthyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetic acid
-
pH 7.2-7.5, 37C
5.2e-05
-
2-[8-chloro-6-(2,3-dichlorobenzoyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetic acid
-
pH 7.2-7.5, 37C
0.00044
-
2-[8-chloro-6-(2,3-dihydro-1,4-benzodioxin-5-yl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetic acid
-
pH 7.2-7.5, 37C
7.6e-06
-
2-[8-chloro-6-(2,3-dimethoxyphenyl)-1-(4-morpholinylmethyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetic acid
-
pH 7.2-7.5, 37C
0.00054
-
2-[8-chloro-6-(2,3-dimethoxyphenyl)-1-[(dimethylamino)methyl]-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetic acid
-
pH 7.2-7.5, 37C
3.3e-06
-
2-[8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetic acid
-
pH 7.2-7.5, 37C
8.5e-07
-
3-(2-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-2H-1,2,3,4-tetrazol-5-yl)propanoic acid
-
pH 7.2-7.5, 37C
0.00073
-
3-(biphenyl-4-ylmethyl)-1-azabicyclo[2.2.2]oct-2-ene
-
IC50: 730 nM
4e-06
-
3-([2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetyl]amino)benzoic acid
-
pH 7.2-7.5, 37C
2.9e-06
-
3-([2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetyl]amino)propionic acid
-
pH 7.2-7.5, 37C
1.4e-06
-
3-[(1-[3-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]propanoyl]-4-piperidinyl)oxy]propanoic acid
-
pH 7.2-7.5, 37C
3.1e-06
-
3-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6Hpyrrolo[1,2-a][4,1]benzoxazepin-4-yl]propionic acid
-
pH 7.2-7.5, 37C
0.00083
-
3-[[4-(benzyloxy)phenyl]ethynyl]-1-azabicyclo[2.2.2]oct-2-ene
-
IC50: 830 nM
1.6e-06
-
4-[3-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]propanoyl]-2-morpholine carboxylic acid
-
pH 7.2-7.5, 37C
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
-
pH and temperature not specified in the publication
0.0001
-
chlorogenic acid
-
pH 7.4, 37C
0.00013
-
CP-294838
P37268
a benzoxazepinone IC50 130 nM
2e-05
-
CP-295697
P37268
a bisphosphonate, IC50: 20 nM
8.4e-07
-
E5700
-
IC50: 0.84 nM
3.52e-06
-
ER119884
-
IC50: 3.52 nM
5e-05
-
ethyl 4-(1-azabicyclo[2.2.2]oct-2-en-3-yl)benzoate
-
IC50: 50 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
-
pH and temperature not specified in the publication
0.00022
-
methyl 2-[8-chloro-6-(2,3-dimethoxyphenyl)-4H,6Hpyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetate
-
pH 7.2-7.5, 37C
7e-07
-
zaragozic acid
P37268
IC50 0.7 nM
-
9.55e-05
-
zaragozic acid A
-
pH 7.2, 37C
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
pH and temperature not specified in the publication
5.6e-05
-
[(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
-
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
-
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
-
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
-
pH and temperature not specified in the publication
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.1
-
-
truncated protein, soluble extract
0.459
-
-
truncated protein, after 4.5fold purification
0.816
-
-
presqualene
0.95
-
-
squalene
15.6
-
-
presqualene
additional information
-
-
assay methods
additional information
-
-
-
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7.2
7.5
-
assay at
7.2
-
-
assay at
7.4
-
-, Q257D4
-
8
-
H9L9T8
assay at
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5.2
8.2
-
pH 5.2: about 45% of maximum activity, pH 8.2: about 75% of maximum activity
6
9
-, Q257D4
activity range, over 90% of maximal activity at pH 7.0-8.0, 30% at pH 6.0, 20% at pH 9.0
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
25
30
-
formation of lycopersene
30
-
-
formation of prelycopersene diphosphate
30
-
H9L9T8
assay at
35
-
-
assay at
37
-
-
assay at
37
-
B9WZW7, -
assay at
37
-
-
assay at
37
-
-, Q257D4
-
TEMPERATURE RANGE
TEMPERATURE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
30
45
-, Q257D4
83% and 88% activity at a temperature of 30C and 45C
pI VALUE
pI VALUE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.5
-
A9NJG0, -
calculated
6.64
-
-, I6Z427
sequence calculation
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
O23118, P53799
petiole of cotyledon
Manually annotated by BRENDA team
O23118, P53799
of seedling
Manually annotated by BRENDA team
-
low activity
Manually annotated by BRENDA team
O23118, P53799
vascular tissue of leaf
Manually annotated by BRENDA team
H9L9T8
higher SQS comtent in younger than in mature leaves
Manually annotated by BRENDA team
A0SJQ5, -
expression level is relatively low in mycelia incubated for 12 days, increases after 14 to 20 days of incubation, and reaches a relatively high level in the mushroom primordia
Manually annotated by BRENDA team
A0SJQ5, -
expression level is relatively low in mycelia incubated for 12 days, increases after 14 to 20 days of incubation, and reaches a relatively high level in the mushroom primordia
Manually annotated by BRENDA team
-
low activity
Manually annotated by BRENDA team
O48666, -
induction of enzyme by methyl jasmonate treatment, enhanced activity results in increase in phytosterols as well as ginsenoside contents
Manually annotated by BRENDA team
A9NJG0, -
highest expression
Manually annotated by BRENDA team
O48666, -
shoot apex
Manually annotated by BRENDA team
additional information
A9NJG0, -
constitutive expression in all tissues examined
Manually annotated by BRENDA team
additional information
O23118, P53799
isoform Sqs1 is widely expressed in all tissues throughout plant development
Manually annotated by BRENDA team
additional information
-
tissue real-time RTPCR expression analysis, the enzyme is expressed constitutively in all tested tissues, with the highest expression in stems
Manually annotated by BRENDA team
additional information
H9L9T8
quantitative real-time PCR tissue expression analysis, overview. WsSQS expresses more in young leaves than mature leaves, stem and root
Manually annotated by BRENDA team
additional information
-, I6Z427
SqS expression is 14.3% higher in leaves compared to roots, semi-quantitative RT-PCR expression analysis, ovverview. CbSqS shows distinct pattern of expression in leaf and root tissues
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
32000
35000
-
gel filtration
41670
-
-
SDS-PAGE, estimated molecular mass
42600
-
-
sucrose density gradient centrifugation, gel filtration
54500
-
-
gel filtration, sucrose density gradient sedimentation
55000
60000
-
gel filtration
55000
-
-
gel filtration
68000
-
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 47000, SDS-PAGE
?
-
x * 44000, expressed in Escherichia coli, SDS-PAGE
?
-
x * 42000-44000, enzyme expressed in Escherichia coli, SDS-PAGE, carboxy-terminal truncated enzyme
?
-
x * 47000, immunoblot analysis of enzyme separated by SDS-PAGE
?
-
x * 32000-33000, trypsin-truncated enzyme, SDS-PAGE
?
-
x * 46700, deduced from gene sequence
?
Q9M678
x * 52500, deduced from gene sequence
?
-
x * 47000, deduced from gene sequence
?
-
x * 42000, SDS-PAGE, x * 41886, electrospray mass spectrometry, x * 39900, calculated
?
A9NJG0, -
x * 46460, calculated
?
H9L9T8
x * 43000, recombinant C-terminally truncated, His6-tagged WsSQS1and WsSQS2, SDS-PAGE
?
-, I6Z427
x * 46000, about, sequence calculation, x * 40000-50000, recombinant enzyme, SDS-PAGE
?
-, Q32R64
x * 47000, about, sequence calculation
monomer
-
1 * 64000, SDS-PAGE
additional information
-, Q84LE3
C-terminal 23 amino acids constitute a transmembrane peptide
additional information
-, Q257D4
sequence comparison, overview
additional information
-, I6Z427
sequence comparisons with other squalene synthases, analysis of reuired structure motifs, three-dimensional structure model, structure-function relationship, overview
additional information
Leishmania donovani MHOM/IN/80/Dd8
-
sequence comparison, overview
-
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
in complex with different inhibitors
P37268
mutant with deletion of 47 C-terminal amino acids
P37268
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
-
pH STABILITY
pH STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
8.5
-
-
irreversible denaturation above
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
25
-
-
in presence of deoxycholate, 5 min, 50% loss of activity
41
-
-
without deoxycholate, 5 min, 50% loss of activity
60
-
-, Q257D4
purified recombinant enzyme, pH 7.4, loss of 85% activity
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
methanol, 10%, does not stabilize
-
sucrose, 10%, does not stabilize
-
a combination of 10% methanol, 10% glycerol, 30 mM octyl-beta-D-glucopyranoside, 0.4% Brij-58, and 1 mM DTT in 25 mM sodium phosphate, pH 7.4, essential for stability and maximal activity
-
markedly stabilized by 30% glycerol and 0.02 M 2-mercaptoethanol
-
methanol stabilizes
-
methanol, 10%, does not stabilize
-
NADPH has no effect on stability
-
octylglucoside, 5 mM, causes rapid loss of activity
-
stable in buffer containing 5 mM octylglucoside and 15 mM CHAPS
-
sucrose stabilizes
-
sucrose, 10%, does not stabilize
-
detergent, e.g. deoxycholate, destabilizes
-
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-80C, stable for at least 6 months
-
-80C, 25 mM sodium phosphate (pH 7.4, containing 20 mM NaCl, 2 mM dithiothreitol, 1 mM EDTA, 40% glycerol, 10% methanol, 1 mM phenylmethylsulfonyl fluoride, 0.01 mM leupeptin, 0.001 mM pepstatin), extended periods of time, no loss of activity
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
recombinant protein
-
recombinant truncated N-terminally His6-tagged SQS(31-370) from Escherichia coli strain BL21(DE3), the tag is cleaved off by thrombin
-
recombinant His6-tagged LdSSN from Escherichia coli strain BL21(DE3) by anion exchange chromatography, nickel affinity chrmatography is not successful
-, Q257D4
trypsin-truncated enzyme
-
expressed in E. coli
-
gel purification and Ni-NTA column purification
-
overexpressed in E. coli
-
recombinant His-tagged protein found exclusively in inclusion bodies. Solubilization in presence of glycerol
-
HiTrap nickel-chelating column chromatography and MonoQ HR5/5 anion-exchange column chromatography
-
recombinant His6-tagged WsSQS1and WsSQS2 proteins from Escherichia coli by nickel affinity chromatgraphy
H9L9T8
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expression as green fluorescent protein-tagged version in onion; expression in Escherichia coli
O23118, P53799
gene BfSS1, overexpression in Bupleurum falcatum using transfection via Agrobacterium tumefaciens strain GV3101
-, Q32R64
gene CbSqS, DNA and amino acid sequence determination and analysis, phylogenetic analysis, expression in Escherichia coli strain M15
-, I6Z427
expression in Escherichia coli
B9WZW7, -
gene fragment SQS(31-370) as N-terminally His6-tagged protein containing a thrombin cleavage site in Escherichia coli strain BL21(DE3)
-
overview
-
LdSSN DNA and amino acid sequence determination and analysis, sequence comparison, phylogenetic analysis, expression as C-terminally His6-tagged protein in Escherichia coli strain BL21 (DE3)
-, Q257D4
-
-, Q84LE3
expressed in Mus musculus C57BL/6
-
enzyme expressed in Escherichia coli
-
development of a plasmid for heterologous expression of yeast squalene synthase in Escherichia coli
-
yeast enzyme overexpressed in Escherichia coli
-
DNA and amino acid sequence determination and analysis, real-time RT-PCR expression analysis
-
clone 8380-1, gene PSS1, DNA and amino acid sequence determination and analysis, overexpression in Solanum tuberosum plants, only four of 12 SQS-transgenics have greater steroidal glycoalkaloid levels than control, quantitative real-time PCR expression analysis
Q9XJ31, -
expression in Escherichia coli, His-tagged protein found exclusively in inclusion bodies
-
expressed in Escherichia coli, several truncated versions of SQS with a His tag attached to the amino terminus
-
cloning in Escherichia coli strain DH5alpha, overexpression of the endogenoous gene encoding squalene synthase in Withania somnifera via transfection with Agrobacterium tumefaciens strain GV3101 using binary vector pBI121
-
genes WsSQS1and WsSQS2, DNA and amino acid sequence determination and analysis, phylogenetic tree, quantitative real-time PCR tissue expression analysis, expression as soluble recombinant enzymes with 24 hydrophobic amino acids deleted from the C-terminus and expressed as His6-tagged proteins in Escherichia coli
H9L9T8
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
BfSS1 mRNA accumulates ubiquitously in plant organs and markedly increases in roots after treatment with methyl jasmonate, abscisic acid, and ethephon
-, Q32R64
infectionn of the plants with Fusarium oxysporum induces the squalene synthase expression
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
K45R
-
single nuceotide polymorphism. Mutation is associated with increased total cholesterol and non-high-density lipoprotein cholesterol. Mutation also influences low-density lipolrotein cholesterol and triglycerides
D280E
-, Q84LE3
enzymic activity slightly above wild-type activity
D280P
-, Q84LE3
enzymic activity about 74% of wild-type activity
D280Q
-, Q84LE3
enzymic activity about 50% of wild-type activity
F285L
-, Q84LE3
no enzymic activity
K45R
-
mutation with influence on total cholesterol and non-HDL-C levels
additional information
O23118, P53799
expression as fusion protein after replacement of the 69 C-terminal residues of SQS2 by the111 C-terminal residues of the Schizosaccharomyces pombe. Like wild-type, the fusion protein has no catalytic activity
additional information
-, Q32R64
expression in sense and antisense orientation, phenotypes, overview
K45R
-
mutation with influence on total cholesterol and non-HDL-C levels
additional information
B9WZW7, -
overexpression in Euphorbia tirucalli transgenic callus lines, increased amount of phytosterol
additional information
A0SJQ5, -
functional complementation Ganoderma lucida squalene synthase in a squalene synthase-deficient strain of Saccharomyces cerevisiae
K45R
-
mutation with influence on total cholesterol and non-HDL-C levels
additional information
P37268
deletion of 30 N-terminal amino acids without effect to activity, additional deletion of 81 to 97 C-terminal amino acids abolishes activity, deletion of only 47 C-terminal amino acids retains activity
synthesis
O48666
overexpression of enzyme in Eleutherococcus senticosus, results in enzyme activity up to 3fold higher than wild-type and increase in phytosterols beta-sitosterol and stigmasterol as well as in triterpene saponin levels
additional information
-
point mutations in conserved regions A, B, C indicate that Tyr171, Asp219, Asp223 are essential for activity and Phe288 may be involved in second step of catalysis
additional information
-
downregulation of expression by replacing its native promoter with the methionine-repressible MET3 promoter. Under certain culture conditions amorphadiene production increases fivefold upon ERG9 repression. With increasing flux to amorphadiene, squalene and ergosterol production each decrease. The levels of these three metabolites are dependent not only upon the level of ERG9 repression, but also the timing of its repression relative to the induction of amorphadiene synthase and genes responsible for enhancing flux to farnesyl diphosphate
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
medicine
-
enzyme may be important during response to infection and inflammation
medicine
-
1-allyl-2-[3-(benzylamino)propoxy]-9H-carbazole shows 50% inhibition of enzyme at 63 nM, significant reduction of both plasma cholesterol and plasma triglyceride levels following oral dosing
medicine
-
potential target for antineoplastic intervention
medicine
-
single nuceotide polymorphism K45R, i.e. rs11549147:A>G is associated with increased total cholesterol and non-high-density lipoprotein cholesterol. Mutation also influences low-density lipolrotein cholesterol and triglycerides
medicine
-
aim of inhibitors in treatment of hypercholesterolemia
medicine
-
attractive target for pharmaceutical discovery in treatment of hypercholestermiae
medicine
-
squalene synthase is a potential target for antilipogenic and antiinfective therapies
drug development
-, Q257D4
LdSSN is a potential drug target for visceral leishmaniasis
drug development
Leishmania donovani MHOM/IN/80/Dd8
-
LdSSN is a potential drug target for visceral leishmaniasis
-
medicine
-
induction of enzyme by a diet containing fluvastatin and cholestyramine
medicine
-
enzyme may be important during response to infection and inflammation