Information on EC 1.14.13.132 - squalene monooxygenase

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

EC NUMBER
COMMENTARY
1.14.13.132
-
RECOMMENDED NAME
GeneOntology No.
squalene monooxygenase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
squalene + NADPH + H+ + O2 = (3S)-2,3-epoxy-2,3-dihydrosqualene + NADP+ + H2O
show the reaction diagram
-
-
-
-
squalene + NADPH + H+ + O2 = (3S)-2,3-epoxy-2,3-dihydrosqualene + NADP+ + H2O
show the reaction diagram
proposed mechanism
-
squalene + NADPH + H+ + O2 = (3S)-2,3-epoxy-2,3-dihydrosqualene + NADP+ + H2O
show the reaction diagram
active site involves the key residues K399, R400, and D407
-
squalene + NADPH + H+ + O2 = (3S)-2,3-epoxy-2,3-dihydrosqualene + NADP+ + H2O
show the reaction diagram
cytochrome P450 17alpha hydroxylase/17,20 lyase CYP17 also catalyzes the reaction of squalene epoxidase
-
squalene + NADPH + H+ + O2 = (3S)-2,3-epoxy-2,3-dihydrosqualene + NADP+ + H2O
show the reaction diagram
aromatic amino acid residues located at the substrate-binding domain of the active-site, e.g. Ph223 and Tyr473, control the stereochemical course of the enzyme reaction, mechanism of regio- and stereo-specific epoxidation of squalene to (3S)2,3-oxidosqualene, overview
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
epoxidation
-
-
-
-
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
Biosynthesis of secondary metabolites
-
diploterol and cycloartenol biosynthesis
-
epoxysqualene biosynthesis
-
Metabolic pathways
-
Sesquiterpenoid and triterpenoid biosynthesis
-
Steroid biosynthesis
-
SYSTEMATIC NAME
IUBMB Comments
squalene,NADPH:oxygen oxidoreductase (2,3-epoxidizing)
A flavoprotein (FAD). This enzyme, together with EC 5.4.99.7 lanosterol synthase, was formerly known as squalene oxidocyclase. The electron donor, NADPH, is coupled via EC 1.6.2.4, NADPH---hemoprotein reductase [5,7].
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
CYP17
-
-
cytochrome P450 17alpha hydroxylase/17,20 lyase
-
-
Erg1 protein
-
-
hydroxylase, squalene
-
-
-
-
oxygenase, squalene mono-
-
-
-
-
SQLE
-
-
squalen expoxidase
-
-
squalene 2,3-oxidocyclase
-
-
-
-
squalene epoxidase
-
-
-
-
squalene epoxidase
-
encoded by gene sqe1 in Arabidopsis thaliana
squalene epoxidase
-
-
squalene epoxidase
-
-
squalene epoxidase
-
-
squalene epoxidase
Q603D5
-
squalene epoxidase
-
-
squalene epoxidase
-
-
squalene epoxidase
-
coding gene PgSQE1, 537 amino acids; coding gene PgSQE2, 545 amino acids
squalene epoxidase
-
-
squalene epoxidase
Q1PID4
-
squalene epoxidase
-
-
squalene epoxidase
-
-
squalene epoxidase
-
-
squalene epoxidase
-
-
squalene epoxidase 1
O65403, O81000, Q9SM02, Q9T064
-
squalene hydroxylase
-
-
-
-
squalene oxydocyclase
-
-
-
-
squalene-2,3-epoxidase
-
-
-
-
squalene-2,3-epoxide cyclase
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9029-62-3
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
gene sq1-1, isozyme SQ1; isozymes SQE1-SQE6
UniProt
Manually annotated by BRENDA team
gene sq1-2, isozyme SQ2; isozymes SQE1-SQE6
UniProt
Manually annotated by BRENDA team
gene sq1-3, isozyme SQ3; isozymes SQE1-SQE6
Q9T064
UniProt
Manually annotated by BRENDA team
gene sq1-4, isozyme SQ4; isozymes SQE1-SQE6
UniProt
Manually annotated by BRENDA team
gene ERG1
-
-
Manually annotated by BRENDA team
HepG2 cells
-
-
Manually annotated by BRENDA team
a basidiomycete, gene erg1
-
-
Manually annotated by BRENDA team
enzyme is depressed in anaerobically grown cells
-
-
Manually annotated by BRENDA team
dermatophyte, 6 sequential isolates from 1 patient, resistant to terbinafine
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
metabolism
-
part of cholesterol synthesis pathway
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(3S)-squalene-2,3-epoxide + AH2 + O2
(3S,22S)-2,3-22,23-dioxidosqualene + A + H2O
show the reaction diagram
-
the wild-type enzyme also catalyzes conversion of (3S)2,3-oxidosqualene to (3S,22S)-2,3-22,23-dioxidosqualene
-
-
?
1,1-bisnorsqualene + NADPH + O2
1,1-bisnor-squalene-2,3-epoxide + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
1-methylsqualene + NADPH + O2
1-methyl-squalene-2,3-epoxide + NADP+ + H2O
show the reaction diagram
-
-
-
?
1-norsqualene + NADPH + O2
1-norsqualene-2,3-epoxide + NADP+ + H2O
show the reaction diagram
-
-
-
?
10,11,14,15-tetrahydrosqualene + NADPH + O2
10,11,14,15-tetrahydro-squalene-2,3-epoxide + NADP+ + H2O
show the reaction diagram
-
-
-
?
10,11-dihydrosqualene + NADPH + O2
10,11-dihydro-squalene-2,3-epoxide + NADP+ + H2O
show the reaction diagram
-
-
-
?
2,3-dihydrosqualene + NADPH + O2
?
show the reaction diagram
-
-
-
-
?
2,3-oxidosqualene + NADPH + O2
2,3,22,23-dioxidosqualene + NADP+ + H2O
show the reaction diagram
-
N-terminal truncated recombinant enzyme
-
?
squalene + AH2 + O2
(3S)-squalene-2,3-epoxide + A + H2O
show the reaction diagram
-
rate-limiting step in chloesterol biosynthesis, aromatic amino acid residues located at the substrate-binding domain of the active-site, e.g. Ph223 and Tyr473, control the stereochemical course of the enzyme reaction, mechanism of regio- and stereo-specific epoxidation of squalene to (3S)2,3-oxidosqualene, overview
-
-
?
squalene + AH2 + O2
(S)-squalene-2,3-epoxide + A + H2O
show the reaction diagram
-
-
-
-
?
squalene + AH2 + O2
(S)-squalene-2,3-epoxide + A + H2O
show the reaction diagram
-
-
-
-
?
squalene + AH2 + O2
(S)-squalene-2,3-epoxide + A + H2O
show the reaction diagram
-, O65403, O81000, Q9SM02, Q9T064
-
-
-
?
squalene + AH2 + O2
(S)-squalene-2,3-epoxide + A + H2O
show the reaction diagram
-, Q1PID4
-
-
-
?
squalene + AH2 + O2
(S)-squalene-2,3-epoxide + A + H2O
show the reaction diagram
-
-
-
-
?
squalene + AH2 + O2
(S)-squalene-2,3-epoxide + A + H2O
show the reaction diagram
-
-
-
-
?
squalene + AH2 + O2
(S)-squalene-2,3-epoxide + A + H2O
show the reaction diagram
-
oxidosqualene or dioxidosqualene appears to be the branching point for primary metabolism and secondary metabolites in basidiomycetes
-
-
?
squalene + AH2 + O2
(S)-squalene-2,3-epoxide + A + H2O
show the reaction diagram
-, O65403, O81000, Q9SM02, Q9T064
production of the precursor for all known angiosperm cyclic triterpenoids, which include membrane sterols, brassinosteroid phytohormones, and non-steroidal triterpenoids, overview
-
-
?
squalene + AH2 + O2
(S)-squalene-2,3-epoxide + A + H2O
show the reaction diagram
-, Q1PID4
rate-limiting enzyme in the triterpene saponins biosynthetic pathway, overview
-
-
?
squalene + AH2 + O2
(S)-squalene-2,3-epoxide + A + H2O
show the reaction diagram
-
the enzyme is involved in ergosterol biosynthesis
-
-
?
squalene + AH2 + O2
(S)-squalene-2,3-epoxide + A + H2O
show the reaction diagram
-
the enzyme contains two highly conserved motifs 1 and 2, which flank the FAD cofactor and form part of the interface between cofactor and substrate binding domains in the structure modelling, substrate binding domain structure, overview
-
-
?
squalene + electron donor + O2
(S)-squalene-2,3-epoxide + oxidized electron donor + H2O
show the reaction diagram
-
-
-
-
?
squalene + electron donor + O2
(S)-squalene-2,3-epoxide + oxidized electron donor + H2O
show the reaction diagram
-
first oxygenase and last nonsterol reaction of sterol biosynthesis
-
-
squalene + electron donor + O2
(S)-squalene-2,3-epoxide + oxidized electron donor + H2O
show the reaction diagram
-
may be rate-limiting step in cholesterol biosynthesis in non-cholesterogenic tissues
-
?
squalene + NAD(P)H + O2
(S)-squalene-2,3-epoxide + NADP+ + H2O
show the reaction diagram
-
-
-
-
squalene + NAD(P)H + O2
(S)-squalene-2,3-epoxide + NADP+ + H2O
show the reaction diagram
-
-
-
?
squalene + NAD(P)H + O2
(S)-squalene-2,3-epoxide + NADP+ + H2O
show the reaction diagram
-
-
-
?
squalene + NAD(P)H + O2
(S)-squalene-2,3-epoxide + NADP+ + H2O
show the reaction diagram
-
-
-
?
squalene + NAD(P)H + O2
(S)-squalene-2,3-epoxide + NADP+ + H2O
show the reaction diagram
-
-
-
?
squalene + NAD(P)H + O2
(S)-squalene-2,3-epoxide + NADP+ + H2O
show the reaction diagram
-
-
-
?
squalene + NAD(P)H + O2
(S)-squalene-2,3-epoxide + NADP+ + H2O
show the reaction diagram
-
-
-
?
squalene + NAD(P)H + O2
(S)-squalene-2,3-epoxide + NADP+ + H2O
show the reaction diagram
-
specific for NADPH
-
-
squalene + NAD(P)H + O2
(S)-squalene-2,3-epoxide + NADP+ + H2O
show the reaction diagram
-
NADPH is preferred
-
?
squalene + NAD(P)H + O2
(S)-squalene-2,3-epoxide + NADP+ + H2O
show the reaction diagram
-
NADPH is preferred
-
?
squalene + NAD(P)H + O2
(S)-squalene-2,3-epoxide + NADP+ + H2O
show the reaction diagram
-
NADH is preferred
-
?
squalene + NAD(P)H + O2
(S)-squalene-2,3-epoxide + NADP+ + H2O
show the reaction diagram
-
NADPH is slightly preferred
-
-
?
squalene + O2 + AH2
2,3 oxidosqualene + A + H2O
show the reaction diagram
-
-
-
-
-
squalene + O2 + AH2
2,3 oxidosqualene + A + H2O
show the reaction diagram
-
-
-
-
?
squalene + reduced acceptor + O2
(S)-squalene-2,3-epoxide + acceptor + H2O
show the reaction diagram
-
-
-
-
?
squalene + reduced acceptor + O2
(S)-squalene-2,3-epoxide + acceptor + H2O
show the reaction diagram
-
-
-
-
?
squalene + reduced acceptor + O2
(S)-squalene-2,3-epoxide + acceptor + H2O
show the reaction diagram
-
-
-
-
?
squalene + reduced acceptor + O2
(S)-squalene-2,3-epoxide + acceptor + H2O
show the reaction diagram
-
epoxidation of squalene is the first step in cholesterol biosynthesis
-
-
?
squalene + reduced acceptor + O2
(S)-squalene-2,3-epoxide + acceptor + H2O
show the reaction diagram
-
epoxidation of squalene is the first step in cholesterol biosynthesis
-
-
?
squalene + reduced acceptor + O2
(S)-squalene-2,3-epoxide + acceptor + H2O
show the reaction diagram
-
epoxidation of squalene is the first step in cholesterol biosynthesis
-
-
?
squalene + reduced cytochrome P450 + H+ + O2
(3S)-squalene-2,3-epoxide + cytochrome P450 + H2O
show the reaction diagram
-, Q603D5
absolutely stereo- and regiospecific reaction, co-reaction with NADPH-cytochrome P450 reductase
-
-
?
squalene + reduced cytochrome P450 + O2
(S)-squalene-2,3-epoxide + cytochrome P450 + H2O
show the reaction diagram
-, Q603D5
first step in the cyclic chloesterol biosynthesis
-
-
?
6,7,18,19-tetrahydrosqualene + NADPH + O2
6,7,18,19-tetrahydro-(S)-squalene-2,3-epoxide
show the reaction diagram
-
-
-
?
additional information
?
-
-
the enzyme activity is associated with cytochrome P450 17alpha hydroxylase/17,20 lyase CYP17 in cholesterol biosynthesis in Leydig cells
-
-
-
additional information
?
-
-
the enzyme affects morphogenesis and drug susceptibilities
-
-
-
additional information
?
-
-
location of the substrate-binding site by binding studies using the photolabeling inhibitor trisnorsqualene alcohol diazoester, key residues are K399, R400, and D407
-
-
-
additional information
?
-
-, O65403, O81000, Q9SM02, Q9T064
Arabidopsis thaliana squalene epoxidase 1 is essential for root and seed development
-
-
-
additional information
?
-
-
squalene epoxidase interacts with NADPH-cytochrome P450 reductase and a second microsomal reductase for the conversion of squalene to 2,3(s)-oxidosqualene and to lanosterol in the cholesterol biosynthesis pathway, overview
-
-
-
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
squalene + AH2 + O2
(3S)-squalene-2,3-epoxide + A + H2O
show the reaction diagram
-
rate-limiting step in chloesterol biosynthesis
-
-
?
squalene + AH2 + O2
(S)-squalene-2,3-epoxide + A + H2O
show the reaction diagram
-
-
-
-
?
squalene + AH2 + O2
(S)-squalene-2,3-epoxide + A + H2O
show the reaction diagram
-
-
-
-
?
squalene + AH2 + O2
(S)-squalene-2,3-epoxide + A + H2O
show the reaction diagram
-
oxidosqualene or dioxidosqualene appears to be the branching point for primary metabolism and secondary metabolites in basidiomycetes
-
-
?
squalene + AH2 + O2
(S)-squalene-2,3-epoxide + A + H2O
show the reaction diagram
-, O65403, O81000, Q9SM02, Q9T064
production of the precursor for all known angiosperm cyclic triterpenoids, which include membrane sterols, brassinosteroid phytohormones, and non-steroidal triterpenoids, overview
-
-
?
squalene + AH2 + O2
(S)-squalene-2,3-epoxide + A + H2O
show the reaction diagram
-, Q1PID4
rate-limiting enzyme in the triterpene saponins biosynthetic pathway, overview
-
-
?
squalene + AH2 + O2
(S)-squalene-2,3-epoxide + A + H2O
show the reaction diagram
-
the enzyme is involved in ergosterol biosynthesis
-
-
?
squalene + electron donor + O2
(S)-squalene-2,3-epoxide + oxidized electron donor + H2O
show the reaction diagram
-
first oxygenase and last nonsterol reaction of sterol biosynthesis
-
-
squalene + electron donor + O2
(S)-squalene-2,3-epoxide + oxidized electron donor + H2O
show the reaction diagram
-
may be rate-limiting step in cholesterol biosynthesis in non-cholesterogenic tissues
-
?
squalene + O2 + AH2
2,3 oxidosqualene + A + H2O
show the reaction diagram
-
-
-
-
?
squalene + reduced acceptor + O2
(S)-squalene-2,3-epoxide + acceptor + H2O
show the reaction diagram
-
epoxidation of squalene is the first step in cholesterol biosynthesis
-
-
?
squalene + reduced acceptor + O2
(S)-squalene-2,3-epoxide + acceptor + H2O
show the reaction diagram
-
epoxidation of squalene is the first step in cholesterol biosynthesis
-
-
?
squalene + reduced acceptor + O2
(S)-squalene-2,3-epoxide + acceptor + H2O
show the reaction diagram
-
epoxidation of squalene is the first step in cholesterol biosynthesis
-
-
?
squalene + reduced cytochrome P450 + O2
(S)-squalene-2,3-epoxide + cytochrome P450 + H2O
show the reaction diagram
-, Q603D5
first step in the cyclic chloesterol biosynthesis
-
-
?
additional information
?
-
-
the enzyme activity is associated with cytochrome P450 17alpha hydroxylase/17,20 lyase CYP17 in cholesterol biosynthesis in Leydig cells
-
-
-
additional information
?
-
-
the enzyme affects morphogenesis and drug susceptibilities
-
-
-
additional information
?
-
-, O65403, O81000, Q9SM02, Q9T064
Arabidopsis thaliana squalene epoxidase 1 is essential for root and seed development
-
-
-
additional information
?
-
-
squalene epoxidase interacts with NADPH-cytochrome P450 reductase and a second microsomal reductase for the conversion of squalene to 2,3(s)-oxidosqualene and to lanosterol in the cholesterol biosynthesis pathway, overview
-
-
-
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
1-Carba-1-deazaFAD
-
can replace FAD as cofactor
cytochrome P450
-
required
-
FAD
-
flavoprotein; required for activity
FAD
-
flavoprotein
FAD
-
required for activity
FAD
-
required for activity
FAD
-
required for activity
FAD
-
FAD is loosely bound
FAD
-
contains two FAD domains
FAD
-
binding domain structure, the enzyme contains two highly conserved motifs 1 and 2, which flank the FAD cofactor and form part of the interface between cofactor and substrate binding domains in the structure modelling, overview
FAD
-
sequence determination of the FAD-binding site with the dinucleotide-binding GXGXXG motif, and DG and GD motif
reduced cytochrome P450
Q603D5
-
-
additional information
-
5-carba-5-deazaFAD cannot replace FAD as cofactor
-
additional information
-
FMN cannot replace FAD as cofactor
-
additional information
-
FAD is not essential for activity, 76.2% activity in the absence of FAD
-
additional information
-
neither FMN nor riboflavin can replace FAD
-
additional information
-
FAD stimulates activity but is not essential
-
additional information
-
electron transfer partner NADPH-cytochrome P450 reductase
-
additional information
-, Q1PID4
the enzyme sequence contains a Rossmann-dinucleotide binding fold and NAD(P)-binding site
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Fe2+
-
a cytochrome P450 enzyme
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(-)-epicatechin-3-O-gallate
-
50% inhibition at 0.0013 mM
(-)-epigallocatechin-3-O-gallate
-
50% inhibition at 0.00069 mM, noncompetitive
(-)-gallocatechin-3-O-gallate
-
50% inhibition at 0.00067 mM
(2R,3R)-2,3-dimethyl-1-(3-phenylprop-2-ynyl)piperidine hydrochloride
-
-
(2R,3S)-2,3-dimethyl-1-(3-phenylprop-2-ynyl)piperidine hydrochloride
-
-
(2R,5R)-2,5-dimethyl-1-(3-phenylprop-2-ynyl)piperidine hydrochloride
-
-
(2R,5S)-2,5-dimethyl-1-(3-phenylprop-2-ynyl)piperidine hydrochloride
-
-
(2R,6R)-2,6-dimethyl-4-(3-phenylprop-2-ynyl)morpholine hydrochloride
-
-
(3R,5R)-3,5-dimethyl-1-(3-phenylprop-2-ynyl)piperidine hydrochloride
-
-
(3R,5S)-3,5-dimethyl-1-(3-phenylprop-2-ynyl)piperidine hydrochloride
-
-
(E)-N-(6,6-Dimethylhept-2-en-4-ynyl)-N-methyl-1-naphthalenemethaneamine hydrochloride
-
i.e. compound SF 86-327, non-competitive inhibition
(E)-N-ethyl-N-(6,6-dimethyl-2-hepten-4-ynyl)-3-[2-methyl-2-(3-thienylmethoxy)propyloxy]benzylamine hydrochloride
-
trivial name FR194738, 0.0000098 mM, 50% inhibition of enzyme activity in HepG2 cell homogenate
(E)-N-Methyl-N-(3-phenylprop-2-enyl)-1-naphthalenemethaneamine
-
i.e. naftifine, non-competitive inhibition
1,2,6-Tri-O-galloyl-beta-D-glucose
-
0.00063 mM, 50% inhibition
1,6-di-O-galloyl-2-O-cinnamoyl-beta-D-glucose
-
0.00058 mM, 50% inhibition
1-[3-(2,3-dichlorophenyl)-prop-2-ynyl]-3-methylpiperidine hydrochloride
-
-
1-[3-(2,4-dichlorophenyl)-prop-2-ynyl]-3-methylpiperidine hydrochloride
-
-
1-[3-(2,5-dichlorophenyl)-prop-2-ynyl]-3-methylpiperidine hydrochloride
-
-
1-[3-(2,6-dichlorophenyl)-prop-2-ynyl]-3-methylpiperidine hydrochloride
-
-
1-[3-(2-chlorophenyl)-prop-2-ynyl]-3-methylpiperidine hydrochloride
-
-
1-[3-(3,4-dichlorophenyl)-prop-2-ynyl]-3-methylpiperidine hydrochloride
-
-
1-[3-(3,4-dichlorophenyl)prop-2-ynyl]-3-ethylpiperidine hydrochloride
-
-
1-[3-(3,5-dichlorophenyl)-prop-2-ynyl]-3-methylpiperidine hydrochloride
-
strong, selective inhibition
1-[3-(3,5-dichlorophenyl)prop-2-ynyl]pyrrolidine hydrochloride
-
-
1-[3-(3,5-difluorophenyl)-prop-2-ynyl]-3-methylpiperidine hydrochloride
-
-
1-[3-(3-chloro-5-methoxyphenyl)-prop-2-ynyl]-3-methylpiperidine hydrochloride
-
-
1-[3-(3-chlorophenyl)-prop-2-ynyl]-3-methylpiperidine hydrochloride
-
-
1-[3-(3-cyanophenyl)-prop-2-ynyl]-3-methylpiperidine hydrochloride
-
-
1-[3-(3-methoxyphenyl)-prop-2-ynyl]-3-methylpiperidine hydrochloride
-
-
1-[3-(3-methylphenyl)-prop-2-ynyl]-3-methylpiperidine hydrochloride
-
-
1-[3-(4-chloro-3-trifluoromethylphenyl)-prop-2-ynyl]-3-methylpiperidine hydrochloride
-
-
1-[3-(4-chlorophenyl)-prop-2-ynyl]-3-methylpiperidine hydrochloride
-
-
1-[3-(4-cyanophenyl)-prop-2-ynyl]-3-methylpiperidine hydrochloride
-
-
1-[3-(4-fluorophenyl)-prop-2-ynyl]-3-methylpiperidine hydrochloride
-
-
1-[3-(4-methylphenyl)-prop-2-ynyl]-3-methylpiperidine hydrochloride
-
-
1-[3-(4-trifluoromethylphenyl)-prop-2-ynyl]-3-methylpiperidine hydrochloride
-
-
2-ethyl-1-(3-phenylprop-2-ynyl)piperidine hydrochloride
-
-
2-methyl-1-(3-phenylprop-2-ynyl)piperidine hydrochloride
-
-
2-propyl-1-(3-phenylprop-2-ynyl)piperidine hydrochloride
-
-
26-hydroxysqualene
-
competitive
3-ethyl-1-(3-phenylprop-2-ynyl)piperidine hydrochloride
-
-
3-methyl-1-(5-phenylpent-2-ynyl)piperidine hydrochloride
-
-
3-methyl-1-[3-(2-naphthyl)prop-2-ynyl]piperidine hydrochloride
-
-
3-methyl-1-[3-(3-thienyl)-prop-2-ynyl]piperidine hydrochloride
-
-
4-(3-phenyl-2-propenyl)piperazine-1-ylamide of 3-(2-furyl)propenoic acid
-
analysing effect on accumulation of more squalen and less (S)-squalene-2,3-epoxide in Trypanosoma cruzi. Analysing antifungal effect on Microsporum canis C 112, Epidermophyton floccosum C 114, Trichophyton rubrum C 110, Trichophyton mentagrophytes ATCC 9972 and Microsporum gypseum C 115
4-(3-phenyl-2-propenyl)piperazine-1-ylamide of 3-(5-nitro2-furyl)propenoic acid
-
analysing effect on accumulation of more squalen and less (S)-squalene-2,3-epoxide in Trypanosoma cruzi. Analysing antifungal effect on Microsporum canis C 112, Epidermophyton floccosum C 114, Trichophyton rubrum C 110, Trichophyton mentagrophytes ATCC 9972 and Microsporum gypseum C 115
4-allyl-1-(3-furyl-2-propenylidene)thiosemicarbazide
-
analysing effect on accumulation of more squalen and less (S)-squalene-2,3-epoxide in Trypanosoma cruzi. Analysing antifungal effect on Microsporum canis C 112, Epidermophyton floccosum C 114, Trichophyton rubrum C 110, Trichophyton mentagrophytes ATCC 9972 and Microsporum gypseum C 115
4-allyl-1-(5-nitrofurfurilydene)thiosemicarbazide
-
analysing effect on accumulation of more squalen and less (S)-squalene-2,3-epoxide in Trypanosoma cruzi. Analysing antifungal effect on Microsporum canis C 112, Epidermophyton floccosum C 114, Trichophyton rubrum C 110, Trichophyton mentagrophytes ATCC 9972 and Microsporum gypseum C 115
4-allyl-1-(5-nitrothenylidene)thiosemicarbazide
-
analysing effect on accumulation of more squalen and less (S)-squalene-2,3-epoxide in Trypanosoma cruzi. Analysing antifungal effect on Microsporum canis C 112, Epidermophyton floccosum C 114, Trichophyton rubrum C 110, Trichophyton mentagrophytes ATCC 9972 and Microsporum gypseum C 115
4-allyl-1-furfurylidenethiosemicarbazide
-
analysing effect on accumulation of more squalen and less (S)-squalene-2,3-epoxide in Trypanosoma cruzi. Analysing antifungal effect on Microsporum canis C 112, Epidermophyton floccosum C 114, Trichophyton rubrum C 110, Trichophyton mentagrophytes ATCC 9972 and Microsporum gypseum C 115
4-allyl-1-thenylidenethiosemicarbazide
-
analysing effect on accumulation of more squalen and less (S)-squalene-2,3-epoxide in Trypanosoma cruzi. Analysing antifungal effect on Microsporum canis C 112, Epidermophyton floccosum C 114, Trichophyton rubrum C 110, Trichophyton mentagrophytes ATCC 9972 and Microsporum gypseum C 115
4-allyl-1-[3-(5-nitro-2-furyl)-2-propenylidene]
-
analysing effect on accumulation of more squalen and less (S)-squalene-2,3-epoxide in Trypanosoma cruzi. Analysing antifungal effect on Microsporum canis C 112, Epidermophyton floccosum C 114, Trichophyton rubrum C 110, Trichophyton mentagrophytes ATCC 9972 and Microsporum gypseum C 115
4-[3-(3-methylpiperidin-1-yl)prop-1-ynyl]benzenesulfonamide hydrochloride
-
-
amorolfine
-
0.03 mM, 50% inhibition
antimycin A
-
0.1 mM, 44% inhibition
Bovine serum albumin
-
-
-
chloromercuriphenylsulfonate
-
1 mM, 35% inhibition
Cu2+
-
5 mM, 99% inhibition
deoxycholate
-
-
diethydithiocarbamate
-
capable of inhibiting the jasmonic acid biosynthesis and depressing the 2-hydroxyethyl jasmonate-induced up-regulation of squalene epoxide gene expression
-
dimethyltelluride
-
approx. 0.0001 mM, 50% inhibition of recombinant enzyme, 0.1 mM, complete inhibition, preincubation with 1 mM glutathione maintains 50% of initial activity
dimethyltellurium dichloride
-
approx. 0.0001 mM, 50% inhibition of recombinant enzyme, 0.1 mM, complete inhibition, preincubation with 1 mM glutathione maintains 50% of initial activity
epicatechin-3-O-gallate
-
0.0013 mM, 50% inhibition
epigallocatechin-3-O-gallate
-
0.00069 mM, 50% inhibition
epigallocatechin-3-O-gallate
-
-
farnesyl gallate
-
0.0015 mM, 50% inhibition
gallocatechin-3-O-gallate
-
0.00067 mM, 50% inhibition
geranyl gallate
-
0.0125 mM, 50% inhibition
geranylgeranyl gallate
-
0.0045 mM, 50% inhibition
H2O2
-
inhibition above 2 mM
Hydroxymercuribenzoate
-
1 mM, 35% inhibition
-
Ketoconazole
-
the sensitive of conserved motif 1 mutant enzymes is increased compared tot he wild-type enzyme
Mega-8
-
0.3%, 19% inhibition
N-(2-hydroxyethyl)-3-(5-nitro-2-furyl)propenamide
-
analysing effect on accumulation of more squalen and less (S)-squalene-2,3-epoxide in Trypanosoma cruzi. Analysing antifungal effect on Microsporum canis C 112, Epidermophyton floccosum C 114, Trichophyton rubrum C 110, Trichophyton mentagrophytes ATCC 9972 and Microsporum gypseum C 115
n-dodecyl gallate
-
0.000061 mM, 50% inhibition
N-ethylmaleimide
-
1 mM, 35% inhibition
N1,N1,2-trimethyl-N2-(3-phenylprop-2-ynyl)propane-1,2-diamine
-
-
naftifine
-
the sensitive of conserved motif 1 mutant enzymes is increased compared tot he wild-type enzyme
NB-598
-
0.045 mM, 50% inhibition, partial non-competitive
NB-598
-
0.0000032 mM, 50% inhibition of microsomal enzyme, 0.0000019 mM, 50% inhibition of N-terminal truncated recombinant enzyme
NB-598
-
squalenoid noncompetitive allylamine inhibitor
NB-598
-
decreases LDL and triglyceride levels, strong side effects (e.g. dermatitis-like toxicity)
NB-598
-
decrease of LDL and triglyceride levels, dermatitis-like toxicity
Phenylarsine oxide
-
recombinant enzyme, glutathione and 2,3-dimercaptopropanol protect almost completely
phenylbutyl gallate
-
0.0613 mM, 50% inhibition
phenyldecyl gallate
-
0.0153 mM, 50% inhibition
phenylhexyl gallate
-
0.0119 mM, 50% inhibition
phenyloctyl gallate
-
0.0125 mM, 50% inhibition
procyanidin B-2 3,3'-di-O-gallate
-
0.00054 mM, 50% inhibition
procyanidin B-5 3,3'-di-O-gallate
-
0.00055 mM, 50% inhibition
rotenone
-
0.1 mM, 67% inhibition
SDZ 87-469
-
0.000020 mM, 50% inhibition
Selenite
-
recombinant enzyme
Selenite
-
0.037 mM, 50% inhibition of recombinant enzyme, 2,3-dimercaptopropanol and dithiothreitol increase inhibition
selenium dioxide
-
recombinant enzyme
tellurite
-
17 mM, 50% non-competitive inhibition of the recombinant enzyme
-
tellurite
-
0.01 mM, 50% inhibition of recombinant enzyme, 10 mM, 95% inhibition, glutathione and 2,3-dimercaptopropanol protect almost completely
-
tellurium dioxide
-
37 mM, 50% inhibition of the recombinant enzyme
terbinafine
-
0.18 mM, 50% inhibition, non-competitive
terbinafine
-
0.0000158 mM, 50% inhibition, non-competitive vs. squalene
terbinafine
-
sensitive strains, residue Leu398 is responsible for the inhibitory effect, mutant L398F is insensitive
terbinafine
-
sensitive strains, residue Leu393 is responsible for the inhibitory effect
terbinafine
-
specific inhibition in a noncompetitive manner
terbinafine
-
the sensitive of conserved motif 1 mutant enzymes is increased compared tot he wild-type enzyme
terbinafine
-
noncompetitive. Analysis of the terbinafine-squalene epoxidase mode of interaction by docking studies followed by molecular dynamics simulations and quantum interaction energy calculations. In the energetically most likely orientation of terbinafine its interaction energy with the protein is ca. 120 kJ/mol. In the favorable position the terbinafine lipophilic moiety is located vertically inside the squalene epoxidase binding pocket with the tert-butyl group oriented toward its center, resulting in squalene epoxidase conformational changes and preventing the natural substrate from being able to bind to the enzyme's active site. Strongest interaction between terbinafine and squalene poxide stems from hydrogen bonding between hydrogen-bond donors, hydroxyl group of Tyr90 and amine nitrogen atom of terbinafine
theasinensin A
-
0.00013 mM, 50% inhibition
theasinensin A
-
50% inhibition at 0.00013 mM
Thiosemicarbazide
-
analysing effect on accumulation of more squalen and less (S)-squalene-2,3-epoxide in Trypanosoma cruzi. Analysing antifungal effect on Microsporum canis C 112, Epidermophyton floccosum C 114, Trichophyton rubrum C 110, Trichophyton mentagrophytes ATCC 9972 and Microsporum gypseum C 115
tolciclate
-
0.000028 mM, 50% inhibition
tolnaftate
-
0.0000515 mM, 50% inhibition
trisnorsqualene alcohol
-
0.004 mM, 50% inhibition
trisnorsqualene alcohol
-
squalenoid noncompetitive inhibitor, mechanism-based inactivator
trisnorsqualene alcohol diazoester
-
i.e. TNSA-Dza, competitive, able to photocovalently modify the native protein
trisnorsqualene cyclopropylamine
-
0.002 mM, 50% inhibition
trisnorsqualene cyclopropylamine
-
squalenoid noncompetitive inhibitor, mechanism-based inactivator
trisnorsqualene difluoromethylidene
-
0.0054 mM, 50% inhibition
trisnorsqualene gallate
-
0.0051 mM, 50% inhibition
trisnorsqualene hydroxylamine
-
mechanism-based inactivator
Triton X-100
-
-
Triton X-100
-
0.02%, 50% inhibition
Triton X-100
-
0.3%, 71% inhibition
methylselenol
-
0.095 mM, 50% inhibition of recombinant enzyme, 1 mM, complete inhibition
additional information
-
strong inhibition by allylamines
-
additional information
-
cholesterol lowering effect of green tea gallocatechins may be attributed to their potent squalene oxidase inhibition; not inhibitory: flavan-3-ols with galloyl group at C-3
-
additional information
-
cholesterol lowering effect of rhubarb, Rhei Rhizoma, Rheum palmatum L. and polygnaceae, galloyl glucoses and galloyl proanthocyanidins may be attributed to their potent squalene oxidase inhibition
-
additional information
-
enzyme provides resistance to the drugs fluconazole, cycloheximide, ketoconazole, amphotericin B, nystatin, and terbafine, the repressable heterozygous ERG1 mutant strain is hypersensitive to the drugs under repressing conditions and increased sensitive, compared to the wild-type, under non-repressing conditions
-
additional information
-
inhibitor SU10603 inhibits the cytochrome P450 17alpha hydroxylase/17,20 lyase activity of CYP17 but not the squalene epoxidase activity
-
additional information
-
diverse derivatives of 3-phenylprop-2-ynylamines, of piperidine and of quinolineare investigated for their inhibitory potency, IC50 values, structure-activity relationship studies, the most effective inhibitor is 1-[3-(3,5-dichlorophenyl)-prop-2-ynyl]-3-methylpiperidine hydrochloride, IC50 values, overview
-
additional information
-
RNA interference of PgSQE1 completely suppresses PgSQE1 transcription and thereby upregulates PgSQE2 expression
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
2-heptyl-4-hydroxyquinoline N-oxide
-
0.1 mM, 236% stimulation
2-hydroxyethyl jasmonate
-
up-regulation of squalene expoxidase gene transcription
NADPH cytochrome c reductase
-
required for activity of N-terminal truncated recombinant enzyme in a concentration-dependent manner
-
octyl beta-D-glucopyranoside
-
0.3%, 42% activation
Triton X-100
-
0.1%, 36fold activation of microsomal enzyme, 0.05%, 34fold activation of N-terminal truncated recombinant enzyme
Triton X-100
Q603D5
activates at 0.1%
Mega-9
-
0.3%, 44% activation
additional information
-
squalene epoxidation system requires a supernatant protein and a phospholipid: requirement for the heat-stable factor can be fully met by phosphatidylserine, phosphatidylglycerol or phosphatidylinositol and partially by other phospholipids, the heat-labile factor required is a protein with 44000 Da
-
additional information
-
purification of a soluble 47000 Da activator of liver squalene epoxidase
-
additional information
-
2 cytoplasmic components can be replaced by Triton X-100
-
additional information
-
reconstitution of squalene epoxidase activity by addition of: NADPH-cytochrome P-450 reductase, EC 1.6.2.4, FAD and Triton X-100
-
additional information
-
enzyme is not a cytochrome P-450 enzyme; reconstitution of squalene epoxidase activity by addition of: NADPH-cytochrome P-450 reductase, EC 1.6.2.4, FAD and Triton X-100
-
additional information
-
soluble protein factor from hog liver stimulates activity
-
additional information
-
105000 g supernatant, 8.5fold activation of microsomal enzyme, 3fold activation of N-terminal truncated recombinant enzyme
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.00425
-
(3S)-squalene-2,3-epoxide
-
pH 7.4, 37C, recombinant His-tagged wild-type enzyme
0.00085
-
1-Carba-1-deazaFAD
-
-
0.00043
-
FAD
-
-
0.3
-
FAD
-
recombinant enzyme
1.4e-05
-
NADPH-cytochrome P450 reductase
-
recombinant enzyme, Km for electron transfer partner NADPH-cytochrone P 450 reductase
-
0.0036
-
squalene
-
N-terminal truncated recombinant enzyme
0.0036
-
squalene
-
-
0.0038
-
squalene
-
37C, pH 7.4
0.00987
-
squalene
-
pH 7.4, 37C, recombinant His-tagged wild-type enzyme
0.011
-
squalene
-
-
0.013
-
squalene
-
-
0.0133
-
squalene
-
-
0.0135
-
squalene
-
-
0.016
-
squalene
-
-
0.05
-
squalene
-
-
7.7
-
squalene
-
recombinant enzyme
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0075
-
(3S)-squalene-2,3-epoxide
-
pH 7.4, 37C, recombinant His-tagged wild-type enzyme
0.0055
-
squalene
-
-
0.0183
-
squalene
-
-
0.0683
-
squalene
-
N-terminal trucated recombinant enzyme
0.076
-
squalene
-
pH 7.4, 37C, recombinant His-tagged wild-type enzyme
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.00074
-
(-)-epigallocatechin-3-O-gallate
-
37C, pH 7.4
3e-05
-
(E)-N-(6,6-Dimethylhept-2-en-4-ynyl)-N-methyl-1-naphthalenemethaneamine hydrochloride
-
-
4e-05
-
(E)-N-(6,6-Dimethylhept-2-en-4-ynyl)-N-methyl-1-naphthalenemethaneamine hydrochloride
-
-
0.077
-
(E)-N-(6,6-Dimethylhept-2-en-4-ynyl)-N-methyl-1-naphthalenemethaneamine hydrochloride
-
-
0.00034
-
(E)-N-Methyl-N-(3-phenylprop-2-enyl)-1-naphthalenemethaneamine
-
-
0.0011
-
(E)-N-Methyl-N-(3-phenylprop-2-enyl)-1-naphthalenemethaneamine
-
-
1.44
-
(E)-N-Methyl-N-(3-phenylprop-2-enyl)-1-naphthalenemethaneamine
-
-
4.1e-07
-
NB-598
-
N-terminal truncated recombinant enzyme
7.5e-05
-
terbinafine
-
-
0.0184
-
trisnorsqualene alcohol diazoester
-
recombinant truncated enzyme mutant, pH 7.4, 37C
0.00074
-
epigallocatechin-3-O-gallate
-
non-competitive, non-time dependent inhibition
additional information
-
additional information
-
inhibition kinetics
-
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
1.2e-05
-
-
activity in microsomes
3.21e-05
-
-
activity in microsomal fraction
0.0001
-
-
activity in cell-free extract
0.00278
-
-
-
0.17
-
-
N-terminal truncated recombinant enzyme
additional information
-
-
-
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7.4
-
-
assay at
7.4
-
-
assay at
7.4
-
Q603D5
assay at
7.4
-
-
assay at
7.5
8.5
-
microsomal and N-terminal truncated recombinant enzyme
7.5
-
-
assay at
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
25
-
Q603D5
assay at
30
37
-
activity in crude extract
pI VALUE
pI VALUE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
8.81
-
-, Q1PID4
sequence calculation
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
PgSQE2 mRNA expression
Manually annotated by BRENDA team
A7VJN1, -
stem, high enzyme content
Manually annotated by BRENDA team
A7VJN1, -
high enzyme content
Manually annotated by BRENDA team
-
tumor cell defective in cytochrome P450 17alpha hydroxylase/17,20 lyase activity
Manually annotated by BRENDA team
-
PgSQE2 mRNA expression
Manually annotated by BRENDA team
-, Q1PID4
high expression level in roots, especially in 3-year-old roots
Manually annotated by BRENDA team
O65403, O81000, Q9SM02, Q9T064
-
Manually annotated by BRENDA team
-
methyl jasmonate treatment enhanced the accumulation of PgSQE1 mRNA
Manually annotated by BRENDA team
-
drought hypersensitive/squalene epoxidase 1-5 mutant has altered sterol composition in roots but wild-type sterol composition in shoots (GC-MS analysis)
Manually annotated by BRENDA team
O65403, O81000, Q9SM02, Q9T064
developing; developing; developing; developing
Manually annotated by BRENDA team
O65403, O81000, Q9SM02, Q9T064
-
Manually annotated by BRENDA team
-
drought hypersensitive/squalene epoxidase 1-5 mutant has altered sterol composition in roots but wild-type sterol composition in shoots (GC-MS analysis)
Manually annotated by BRENDA team
A7VJN1, -
high enzyme content, tissue distribution, in situ analysis, overview
Manually annotated by BRENDA team
-
PgSQE2 mRNA expression
Manually annotated by BRENDA team
-
PgSQE1 mRNA abundantly accumulated in all organs
Manually annotated by BRENDA team
additional information
-
very low activity in non-cholesterogenic tissues: brain, muscle, lung, placenta, kidney
Manually annotated by BRENDA team
additional information
-
cell suspension
Manually annotated by BRENDA team
additional information
-, Q1PID4
quantitative expression analysis
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
45000
-
-
sucrose density gradient centrifugation
100000
-
-
recombinant truncated mutant enzyme
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 47000, SDS-PAGE
?
-
x * 55300, Erg1 protein, SDS-PAGE
?
-
x * 48000-50000 + x * 28000-30000, recombinant His-tagged cytochrome P450 17alpha hydroxylase/17,20 lyase CYP17, SDS-PAGE
?
-
x * 64000
?
-, Q1PID4
x * 59140, sequence calculation
dimer
-
2 * 50000, recombinant truncated mutant enzyme, SDS-PAGE
monomer
-
1 * 51000, most of the enzyme behaves as a monomer, SDS-PAGE
additional information
-
enzyme system consists of squalene epoxidase which is distinct from hemoproteins such as cytochrome P-450 isozymes, and a flavoprotein identical with NADPH-cytochrome P-450 reductase
additional information
-
enzyme structure homology modelling using the crystal structure of p-hydroxybenzoate hydroxylase, PHBH, from Pseudomonas fluorescens
additional information
-
enzyme structure modelling, overview
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
analysis of the terbinafine-squalene epoxidase mode of interaction by docking studies followed by molecular dynamics simulations and quantum interaction energy calculations. In the energetically most likely orientation of terbinafine its interaction energy with the protein is ca. 120 kJ/mol. In the favorable position the terbinafine lipophilic moiety is located vertically inside the squalene epoxidase binding pocket with the tert-butyl group oriented toward its center, resulting in squalene epoxidase conformational changes and preventing the natural substrate from being able to bind to the enzyme's active site. Strongest interaction between terbinafine and squalene poxide stems from hydrogen bonding between hydrogen-bond donors, hydroxyl group of Tyr90 and amine nitrogen atom of terbinafine
-
homology model of enzyme based on p-hydroxybenzoate hydroxylase from Pseudomonas fluorescens
-
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
freezing and thawing once, 20% loss of activity
-
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-20C, 5 d, 75% loss of activity
-
stable for several months in liquid nitrogen
-
-70C, 20 mM Tris-HCl buffer, pH 7.4, 0.5% Triton X-100, several weeks
-
-70C, 50 mM Tris-HCl buffer, pH 7.4, 0.5% Triton X-100, several weeks
-
-25C, overnight, 2fold decrease of activity in crude extracts
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
recombinant enzyme
-
DEAE-cellulose, alumina gel, hydroxylapatite, CM-Sephadex C-50, Blue Sepharose 4B
-
partially, preparation of the postmitochondrial supernatant fraction
-
recombinant enzyme, Ni-NTA-agarose, Blue Sepharose CL-6B
-
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
-
solubilization
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
Arabidopsis drought hypersensitive/squalene epoxidase 1-5 mutant is extremely hypersensitivity to drought stress (squalene epoxidase knocked out), stomatal and root defects of the mutant are associated with altered production of reactive oxygen species
-
gene sq1-1 encoding isozyme SQ1, DNA and amino acid sequence determination and analysis, phylogenetic analysis, expression in enzyme-deficient Saccharomyces cerevisiae strain RXY6.2; gene sq1-1 encoding isozyme SQ1, DNA and amino acid sequence determination and analysis, phylogenetic analysis, expression in enzyme-deficient Saccharomyces cerevisiae strain RXY6.2; gene sq1-2 encoding isozyme SQ2, DNA and amino acid sequence determination and analysis, phylogenetic analysis, expression in enzyme-deficient Saccharomyces cerevisiae strain RXY6.2; gene sq1-4 encoding isozyme SQ4, DNA and amino acid sequence determination and analysis, phylogenetic analysis, expression in enzyme-deficient Saccharomyces cerevisiae strain RXY6.2
O65403, O81000, Q9SM02, Q9T064
expression of mutant L398F in Saccharomyces cerevisiae strain INVSc1
-
gene ERG1, subcloning in Escherichi acoli strain DH5alpha
-
single-copy gene, DNA and amino acid sequence determination and analysis, expression in and complementation of erg1-disrupted Saccharomyces cerevisiae mutant strain KLN1
A7VJN1, -
expression of cDNA in Escherichia coli
-
mRNA expression of squalene epoxidase is associated with ER+ 7p+/8q+ breast cancer (mRNA analysis of tumor patients)
-
DNA and amino acid sequence determination and analysis, functional expression in Escherichia coli strain BL21(DE3)
Q603D5
expression of His-tagged cytochrome P450 17alpha hydroxylase/17,20 lyase CYP17 in Escherichia coli
-
methyl jasmonate treatment suppresses PgSQE2 mRNA expression
-
DNA and amino acid sequence determination and analysis, quantitative expression analysis, phylogenetic tree
-, Q1PID4
DNA and amino acid sequence determination and analysis, expression of His-tagged wild-type and mutant enzymes in Escherichia coli strain BL21(DE3)
-
expression of cDNA in Escherichia coli
-
expression of His-tagged wild-type and mutant enzymes in Escherichia coli strain BL21(DE3)
-
expression of wild-type and mutant enzymes in erg1-knockout strain KLN1
-
DNA and amino acid sequence determination and analysis of terbinafine-resistant strains/patient isolates
-
cloning from mycelial powder, DNA and amino acid sequence determination and analysis, sequence comparisons
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
D407F
-
site-directed mutagenesis, mutant shows 8% of wild-type activity
F203A
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
F223A
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme, the F223A mutant no longer accepts (3S)2,3-oxidosqualene as a substrate
F228A
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
F287A
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
F305A
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
F375A
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
F476A
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
F491A
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
F522A
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
F523A
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
K399F
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site-directed mutagenesis, mutant shows 28% of wild-type activity
K399F/R400F/D407F
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site-directed mutagenesis, triple mutant shows 10% of wild-type activity
K399P/R400P/D407P
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site-directed mutagenesis, triple mutant shows 10% of wild-type activity
R400F
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site-directed mutagenesis, mutant shows 24% of wild-type activity
Y194A
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
Y209A
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
Y334A
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
Y473A
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme, the mutant converts (3S)2,3-oxidosqualene to (3S,22S)2,3-22,23-dioxidosqualene twice more efficiently than wild-type enzyme
Y493A
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
Y528A
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
D335F
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mutation in FAD II binding site, nonfunctional enzyme; random mutagenesis, mutation in the FADII site, inactive mutant
D335P
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mutation in FAD II binding site, nonfunctional enzyme; random mutagenesis, mutation in the FADII site, inactive mutant
D335W
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mutation in FAD II binding site, nonfunctional enzyme; random mutagenesis, mutation in the FADII site, inactive mutant
E60A
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site-directed mutagenesis in the highly conserved motif 1, the E60A variant poorly complements growth of KLN1, and shows reduced activity and about 50fold increased sensitivity to terbinafine and naftifine and 5fold to ketoconazole compared to that in the wild type, and confers temperature-sensitive growth
E60Q
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site-directed mutagenesis in the highly conserved motif 1, the E60A variant poorly complements growth of KLN1, and shows highly reduced activity and about 50fold increased sensitivity to terbinafine and naftifine and 5fold to ketoconazole compared to that in the wild type, and confers temperature-sensitive growth
G210A
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mutation in nucleotide binding site, nonfunctional enzyme; random mutagenesis, mutation in the NB site, inactive mutant
G25S
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mutation in FAD I binding site, nonfunctional enzyme; random mutagenesis, mutation in the FADI site, inactive mutant
G30S
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decrease in enzyme activity, sevenfold increase in enzyme mRNA level. Cells exhibit altered sterol composition and increased sensitivity to allylamines and other ergosterol biosynthesis inhibitors; random mutagenesis, the mutant shows highly reduced activity compared to the wild-type enzyme, but a 7fold increased erg1 mRNA level and altered ergosterol composotion, the mutation renders KLN1 more sensitive not only to allylamines but also to other ergosterol biosynthesis inhibitors
G345A
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site-directed mutagenesis, the mutation of the highly conserved motif 2 results in increased allylamine sensitivity without cross-sensitivity to ketoconazole, decreased enzyme activity, and induced Erg1p levels compared to the wild-type enzyme
G346A
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the mutant exhibits wild-type enzyme activity, steady-state protein levels, and naftifine and ketoconazole sensitivity, but is less sensitive toward terbinafine
G66A
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site-directed mutagenesis in the highly conserved motif 1, the mutant shows increased allylamine sensitivity compared to the wild-type enzyme
L37P
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decrease in enzyme activity, sevenfold increase in enzyme mRNA level. Cells exhibit altered sterol composition and increased sensitivity to allylamines and other ergosterol biosynthesis inhibitors; random mutagenesis, the mutant shows highly reduced activity compared to the wild-type enzyme, but a 7fold increased erg1 mRNA level and altered ergosterol composotion, the mutation renders KLN1 more sensitive not only to allylamines but also to other ergosterol biosynthesis inhibitors
R269
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site-directed mutagenesis, the mutant enzyme shows increased allylamine sensitivity
R269G
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decrease in enzyme activity. Cells exhibit increased sensitivity to allylamines, but not to other ergosterol biosynthesis inhibitors; random mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme and a 5-10fold increase in allylamine sensitivity but no cross-sensitivity to the other ergosterol biosynthesis inhibitors
R340A
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site-directed mutagenesis in the highly conserved motif 2, the mutant enzyme shows highly reduced activity compared to the wild-type enzyme
L393F
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terbinafine-resistant strains/patient isolates all contain this missense point mutation responsible for the resistance to the drug
additional information
O65403, O81000, Q9SM02, Q9T064
construction of mutant transgenic plants with defective isozyme SQ1 using the Agrobacterium tumefaciens GV3101 transfection method, sqe1 mutants show severe developmental defects, including reduced root and hypocotyl elongation, adult sqe1-3 and sqe1-4 plants have diminished stature and produce inviable seeds, the sqe1-3 mutant accumulates squalene, consistent with a block in the triterpenoid biosynthetic pathway, phenotypes, overview; construction of mutant transgenic plants with defective isozyme SQ2 using the Agrobacterium tumefaciens GV3101 transfection method, sqe1 mutants show severe developmental defects, including reduced root and hypocotyl elongation, adult sqe1-3 and sqe1-4 plants have diminished stature and produce inviable seeds, the sqe1-3 mutant accumulates squalene, consistent with a block in the triterpenoid biosynthetic pathway, phenotype, overview; construction of mutant transgenic plants with defective isozyme SQ3 using the Agrobacterium tumefaciens GV3101 transfection method, sqe1 mutants show severe developmental defects, including reduced root and hypocotyl elongation, adult sqe1-3 and sqe1-4 plants have diminished stature and produce inviable seeds, the sqe1-3 mutant accumulates squalene, consistent with a block in the triterpenoid biosynthetic pathway. Homozygous sqe1-3 plants are completely infertile whether grown in soil or hydroponically. eed pods of sqe1-3 plants grown hydroponically elongated nearly normally, but sqe1-3 siliques are slightly thinner than wild type and contained shriveled, inviable seeds, phenotypes, overview; construction of mutant transgenic plants with defective isozyme SQ4 using the Agrobacterium tumefaciens GV3101 transfection method, sqe1 mutants show severe developmental defects, including reduced root and hypocotyl elongation, adult sqe1-3 and sqe1-4 plants have diminished stature and produce inviable seeds, the sqe1-3 mutant accumulates squalene, consistent with a block in the triterpenoid biosynthetic pathway, phenotypes, overview
L398F
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site-directed mutagenesis, introduction of the mutation equivalent to L393F found in terbinafine-resistant Trichophyton rubrum strains, mutation renders Saccharomyces cerevisiae strain INVSc1 expressing the recombinant Candida albicans enzyme insensitive to terbafine
additional information
-
construction of a disruption mutant of both gene ERG1 alleles, which is lethal, and of a heterozygous ERG1 disruptant mutant by disruption of one ERG1 allele, while the second is controlled by the regulable promotor MET3p repressable by methionine and cysteine, the heterozyygous mutant strain does not produce ergosterol, conditional mutant shows reduced passive diffusion of drug into the cells, hyphal morphogenesis is affected in the mutant, overview
additional information
-
erg1 silencing in Hypholoma sublateritium, by expression of constructions using the gdh promoter of Agaricus bisporus, results in an ergosterol-dependnet phenotype for full growth, overexpression of erg1 results in 32%-97% increment of clavaric acid production, overview
additional information
-
knockout of cytochrome P450 17alpha hydroxylase/17,20 lyase CYP17 shows dramatically reduced de novo synthesis of steroids, e.g. progesterone, which can partially be rescued by transfection of CYP17, the latter cells can synthesize progesterone if supplemented with precusors squalene epoxide, lanosterol, zymosterol, and desmosterol, but not squalene
additional information
-
in hepatocytes deficent for NADPH-cytochrome P450 reductase, the second microsomal reductase retains about 40% of the full activity for conversion of squalene to 2,3(s)-oxidosqualene with squalene monooxygenase, overview
K399W/R400W/D407W
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site-directed mutagenesis, inactive mutant
additional information
-
construction of a truncated enzyme mutant
M348A
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site-directed mutagenesis in the highly conserved motif 2, the mutant is more sensitive toward terbinafine and naftifine and slightly more sensitive toward ketoconazole compared to the wild-type enzyme, while enzyme activity is reduced and protein levels are induced
additional information
-
isolation of erg1 allele mutants that confer increased terbinafine sensitivity or that show a lethal phenotype when they are expressed in erg1-knockout strain KLN1, overview
additional information
-
amino acid substitutions in both highly conserved motifs 1 and 2 regions reduce enzyme activity and/or alter allylamine sensitivity, overview
Renatured/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
reconstitution of purified enzyme with the addition of NADPH-cytochrome P450 reductase, FAD and Triton X-100
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APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
drug development
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possible enzyme to inhibit for treatment of hypercholesterolemia, but strong side effects (e.g. dermatitis-like toxicity)
medicine
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cholesterol lowering effect of green tea may be attributed to the enzyme inhibitory activities of its gallocatechins