Information on EC 1.14.14.17 - squalene monooxygenase

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

EC NUMBER
COMMENTARY hide
1.14.14.17
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RECOMMENDED NAME
GeneOntology No.
squalene monooxygenase
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
squalene + [reduced NADPH-hemoprotein reductase] + O2 = (3S)-2,3-epoxy-2,3-dihydrosqualene + [oxidized NADPH-hemoprotein reductase] + H2O
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
epoxidation
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-
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oxidation
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-
-
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redox reaction
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reduction
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Biosynthesis of antibiotics
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Biosynthesis of secondary metabolites
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diploterol and cycloartenol biosynthesis
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epoxysqualene biosynthesis
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Metabolic pathways
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Sesquiterpenoid and triterpenoid biosynthesis
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Steroid biosynthesis
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cholesterol biosynthesis
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SYSTEMATIC NAME
IUBMB Comments
squalene,NADPH-hemoprotein: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 is EC 1.6.2.4, NADPH---hemoprotein reductase [5,7].
CAS REGISTRY NUMBER
COMMENTARY hide
9029-62-3
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
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Manually annotated by BRENDA team
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UniProt
Manually annotated by BRENDA team
a basidiomycete, gene erg1
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
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
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-
-
-
?
2,3-oxidosqualene + NADPH + O2
2,3,22,23-dioxidosqualene + NADP+ + H2O
show the reaction diagram
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N-terminal truncated recombinant enzyme
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?
6,7,18,19-tetrahydrosqualene + NADPH + O2
6,7,18,19-tetrahydro-(S)-squalene-2,3-epoxide
show the reaction diagram
-
-
-
?
squalene + AH2 + O2
(3S)-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 + electron donor + O2
(S)-squalene-2,3-epoxide + oxidized electron donor + H2O
show the reaction diagram
squalene + NAD(P)H + O2
(S)-squalene-2,3-epoxide + NADP+ + 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 cytochrome P450 + H+ + O2
(3S)-squalene-2,3-epoxide + cytochrome P450 + H2O
show the reaction diagram
absolutely stereo- and regiospecific reaction, co-reaction with NADPH-cytochrome P450 reductase
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-
?
squalene + reduced cytochrome P450 + O2
(S)-squalene-2,3-epoxide + cytochrome P450 + H2O
show the reaction diagram
first step in the cyclic chloesterol biosynthesis
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-
?
squalene + [reduced NADPH-hemoprotein reductase] + O2
(3S)-2,3-epoxy-2,3-dihydrosqualene + [oxidized NADPH-hemoprotein reductase] + H2O
show the reaction diagram
additional information
?
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
squalene + AH2 + O2
(3S)-squalene-2,3-epoxide + A + H2O
show the reaction diagram
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rate-limiting step in chloesterol biosynthesis
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?
squalene + AH2 + O2
(S)-squalene-2,3-epoxide + A + H2O
show the reaction diagram
squalene + electron donor + O2
(S)-squalene-2,3-epoxide + oxidized electron donor + 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 cytochrome P450 + O2
(S)-squalene-2,3-epoxide + cytochrome P450 + H2O
show the reaction diagram
Q603D5
first step in the cyclic chloesterol biosynthesis
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-
?
squalene + [reduced NADPH-hemoprotein reductase] + O2
(3S)-2,3-epoxy-2,3-dihydrosqualene + [oxidized NADPH-hemoprotein reductase] + H2O
show the reaction diagram
additional information
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1-Carba-1-deazaFAD
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can replace FAD as cofactor
cytochrome P450
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required
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NADPH
reduced cytochrome P450
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additional information
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Fe2+
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a cytochrome P450 enzyme
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(-)-epicatechin-3-O-gallate
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50% inhibition at 0.0013 mM
(-)-epigallocatechin-3-O-gallate
(-)-gallocatechin-3-O-gallate
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50% inhibition at 0.00067 mM
(2R,3R)-2,3-dimethyl-1-(3-phenylprop-2-ynyl)piperidine hydrochloride
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(2R,3S)-2,3-dimethyl-1-(3-phenylprop-2-ynyl)piperidine hydrochloride
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(2R,5R)-2,5-dimethyl-1-(3-phenylprop-2-ynyl)piperidine hydrochloride
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(2R,5S)-2,5-dimethyl-1-(3-phenylprop-2-ynyl)piperidine hydrochloride
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(2R,6R)-2,6-dimethyl-4-(3-phenylprop-2-ynyl)morpholine hydrochloride
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(3R,5R)-3,5-dimethyl-1-(3-phenylprop-2-ynyl)piperidine hydrochloride
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(3R,5S)-3,5-dimethyl-1-(3-phenylprop-2-ynyl)piperidine hydrochloride
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(E)-N-(6,6-dimethylhept-2-en-4-ynyl)-N-methyl-1-naphthalenemethaneamine hydrochloride
(E)-N-ethyl-N-(6,6-dimethyl-2-hepten-4-ynyl)-3-[2-methyl-2-(3-thienylmethoxy)propyloxy]benzylamine hydrochloride
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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
1,2,6-Tri-O-galloyl-beta-D-glucose
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0.00063 mM, 50% inhibition
1,6-di-O-galloyl-2-O-cinnamoyl-beta-D-glucose
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0.00058 mM, 50% inhibition
1-[3-(2,3-dichlorophenyl)-prop-2-ynyl]-3-methylpiperidine hydrochloride
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1-[3-(2,4-dichlorophenyl)-prop-2-ynyl]-3-methylpiperidine hydrochloride
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1-[3-(2,5-dichlorophenyl)-prop-2-ynyl]-3-methylpiperidine hydrochloride
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1-[3-(2,6-dichlorophenyl)-prop-2-ynyl]-3-methylpiperidine hydrochloride
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1-[3-(2-chlorophenyl)-prop-2-ynyl]-3-methylpiperidine hydrochloride
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1-[3-(3,4-dichlorophenyl)-prop-2-ynyl]-3-methylpiperidine hydrochloride
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1-[3-(3,4-dichlorophenyl)prop-2-ynyl]-3-ethylpiperidine hydrochloride
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1-[3-(3,5-dichlorophenyl)-prop-2-ynyl]-3-methylpiperidine hydrochloride
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strong, selective inhibition
1-[3-(3,5-dichlorophenyl)prop-2-ynyl]pyrrolidine hydrochloride
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1-[3-(3,5-difluorophenyl)-prop-2-ynyl]-3-methylpiperidine hydrochloride
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1-[3-(3-chloro-5-methoxyphenyl)-prop-2-ynyl]-3-methylpiperidine hydrochloride
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1-[3-(3-chlorophenyl)-prop-2-ynyl]-3-methylpiperidine hydrochloride
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1-[3-(3-cyanophenyl)-prop-2-ynyl]-3-methylpiperidine hydrochloride
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1-[3-(3-methoxyphenyl)-prop-2-ynyl]-3-methylpiperidine hydrochloride
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1-[3-(3-methylphenyl)-prop-2-ynyl]-3-methylpiperidine hydrochloride
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1-[3-(4-chloro-3-trifluoromethylphenyl)-prop-2-ynyl]-3-methylpiperidine hydrochloride
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1-[3-(4-chlorophenyl)-prop-2-ynyl]-3-methylpiperidine hydrochloride
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1-[3-(4-cyanophenyl)-prop-2-ynyl]-3-methylpiperidine hydrochloride
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1-[3-(4-fluorophenyl)-prop-2-ynyl]-3-methylpiperidine hydrochloride
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1-[3-(4-methylphenyl)-prop-2-ynyl]-3-methylpiperidine hydrochloride
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1-[3-(4-trifluoromethylphenyl)-prop-2-ynyl]-3-methylpiperidine hydrochloride
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2-ethyl-1-(3-phenylprop-2-ynyl)piperidine hydrochloride
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2-methyl-1-(3-phenylprop-2-ynyl)piperidine hydrochloride
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2-propyl-1-(3-phenylprop-2-ynyl)piperidine hydrochloride
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26-hydroxysqualene
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competitive
3-ethyl-1-(3-phenylprop-2-ynyl)piperidine hydrochloride
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3-methyl-1-(5-phenylpent-2-ynyl)piperidine hydrochloride
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3-methyl-1-[3-(2-naphthyl)prop-2-ynyl]piperidine hydrochloride
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3-methyl-1-[3-(3-thienyl)-prop-2-ynyl]piperidine hydrochloride
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4-(3-phenyl-2-propenyl)piperazine-1-ylamide of 3-(2-furyl)propenoic acid
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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
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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
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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
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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
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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
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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
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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]
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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
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amorolfine
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0.03 mM, 50% inhibition
antimycin A
-
0.1 mM, 44% inhibition
bovine serum albumin
-
-
-
chloromercuriphenylsulfonate
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1 mM, 35% inhibition
Cu2+
-
5 mM, 99% inhibition
deoxycholate
-
-
diethydithiocarbamate
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capable of inhibiting the jasmonic acid biosynthesis and depressing the 2-hydroxyethyl jasmonate-induced up-regulation of squalene epoxide gene expression
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dimethyltelluride
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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
dodecyl gallate
epicatechin-3-O-gallate
-
0.0013 mM, 50% inhibition
epigallocatechin-3-O-gallate
farnesyl gallate
-
0.0015 mM, 50% inhibition
FR 194738
-
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
methylselenol
-
0.095 mM, 50% inhibition of recombinant enzyme, 1 mM, complete 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
Pharma Project 4501
-
-
-
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
selenium dioxide
-
recombinant enzyme
tellurite
-
tellurium
tellurium dioxide
-
37 mM, 50% inhibition of the recombinant enzyme
terbinafine
theasinensin A
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
tris norsqualene alcohol
tris norsqualene cyclopropylamine
trisnorsqualene alcohol
trisnorsqualene alcohol diazoester
-
i.e. TNSA-Dza, competitive, able to photocovalently modify the native protein
trisnorsqualene cyclopropylamine
trisnorsqualene difluoromethylidene
-
0.0054 mM, 50% inhibition
trisnorsqualene gallate
-
0.0051 mM, 50% inhibition
trisnorsqualene hydroxylamine
-
mechanism-based inactivator
Triton X-100
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-heptyl-4-hydroxyquinoline N-oxide
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0.1 mM, 236% stimulation
2-hydroxyethyl jasmonate
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up-regulation of squalene expoxidase gene transcription
Mega-9
-
0.3%, 44% activation
NADPH cytochrome c reductase
-
required for activity of N-terminal truncated recombinant enzyme in a concentration-dependent manner
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octyl beta-D-glucopyranoside
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0.3%, 42% activation
Triton X-100
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00425
(3S)-squalene-2,3-epoxide
-
pH 7.4, 37°C, recombinant His-tagged wild-type enzyme
0.00085
1-Carba-1-deazaFAD
-
-
0.00043 - 0.3
FAD
0.000014
NADPH-cytochrome P450 reductase
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recombinant enzyme, Km for electron transfer partner NADPH-cytochrone P 450 reductase
-
0.0036 - 7.7
squalene
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0075
(3S)-squalene-2,3-epoxide
Rattus norvegicus
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pH 7.4, 37°C, recombinant His-tagged wild-type enzyme
0.0055 - 0.076
squalene
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00074
(-)-epigallocatechin-3-O-gallate
-
37°C, pH 7.4
0.00003 - 0.077
(E)-N-(6,6-dimethylhept-2-en-4-ynyl)-N-methyl-1-naphthalenemethaneamine hydrochloride
0.00034 - 1.44
(E)-N-methyl-N-(3-phenylprop-2-enyl)-1-naphthalenemethaneamine
0.00074
epigallocatechin-3-O-gallate
-
non-competitive, non-time dependent inhibition
0.00000041 - 0.0087
NB-598
0.000075
terbinafine
-
-
0.004
tris norsqualene alcohol
-
pH and temperature not specified in the publication
0.002
tris norsqualene cyclopropylamine
-
pH and temperature not specified in the publication
0.0184
trisnorsqualene alcohol diazoester
-
recombinant truncated enzyme mutant, pH 7.4, 37°C
additional information
additional information
-
inhibition kinetics
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000061
dodecyl gallate
Sus scrofa
-
pH and temperature not specified in the publication
0.0000098
FR 194738
Sus scrofa
-
pH and temperature not specified in the publication
-
0.0000044
NB-598
Rattus norvegicus
-
pH and temperature not specified in the publication
0.0009
terbinafine
Arabidopsis thaliana
-
pH and temperature not specified in the publication
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.000012
-
activity in microsomes
0.0000321
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activity in microsomal fraction
0.0001
-
activity in cell-free extract
0.17
-
N-terminal truncated recombinant enzyme
additional information
-
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5 - 8.5
-
microsomal and N-terminal truncated recombinant enzyme
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30 - 37
-
activity in crude extract
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
8.81
sequence calculation
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
PgSQE2 mRNA expression
Manually annotated by BRENDA team
-
primary
Manually annotated by BRENDA team
stem, high enzyme content
Manually annotated by BRENDA team
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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
developing; developing; developing; developing
Manually annotated by BRENDA team
high enzyme content, tissue distribution, in situ analysis, overview
Manually annotated by BRENDA team
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PgSQE2 mRNA expression
Manually annotated by BRENDA team
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PgSQE1 mRNA abundantly accumulated in all organs
Manually annotated by BRENDA team
additional information
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
45000
-
sucrose density gradient centrifugation
47000
-
x * 47000, SDS-PAGE
50000
-
2 * 50000, recombinant truncated mutant enzyme, SDS-PAGE
51000
-
1 * 51000, most of the enzyme behaves as a monomer, SDS-PAGE
55300
-
x * 55300, Erg1 protein, SDS-PAGE
59140
x * 59140, sequence calculation
100000
-
recombinant truncated mutant enzyme
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
-
2 * 50000, recombinant truncated mutant enzyme, SDS-PAGE
monomer
additional information
Crystallization/COMMENTARY
ORGANISM
UNIPROT
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
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homology model of enzyme based on p-hydroxybenzoate hydroxylase from Pseudomonas fluorescens
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
freezing and thawing once, 20% loss of activity
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Treatment with 0.1-0.2 mM unsaturated fatty acids such as oleate, but not saturated fatty acids, increases protein levels of the enzyme at the post-translational level
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, 5 d, 75% loss of activity
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-25°C, overnight, 2fold decrease of activity in crude extracts
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-70°C, 20 mM Tris-HCl buffer, pH 7.4, 0.5% Triton X-100, several weeks
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-70°C, 50 mM Tris-HCl buffer, pH 7.4, 0.5% Triton X-100, several weeks
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stable for several months in liquid nitrogen
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
DEAE-cellulose, alumina gel, hydroxylapatite, CM-Sephadex C-50, Blue Sepharose 4B
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partially, preparation of the postmitochondrial supernatant fraction
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recombinant enzyme
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recombinant enzyme, Ni-NTA-agarose, Blue Sepharose CL-6B
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recombinant His-tagged wild-type and mutant enzymes from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
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solubilization
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Cloned/COMMENTARY
ORGANISM
UNIPROT
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
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cloning from mycelial powder, DNA and amino acid sequence determination and analysis, sequence comparisons
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DNA and amino acid sequence determination and analysis of terbinafine-resistant strains/patient isolates
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DNA and amino acid sequence determination and analysis, expression of His-tagged wild-type and mutant enzymes in Escherichia coli strain BL21(DE3)
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DNA and amino acid sequence determination and analysis, functional expression in Escherichia coli strain BL21(DE3)
DNA and amino acid sequence determination and analysis, quantitative expression analysis, phylogenetic tree
expressed in CHO-7 and HEK-293 cells
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expressed in HEK-293 cells
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expression of cDNA in Escherichia coli
expression of His-tagged cytochrome P450 17alpha hydroxylase/17,20 lyase CYP17 in Escherichia coli
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expression of His-tagged wild-type and mutant enzymes in Escherichia coli strain BL21(DE3)
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expression of mutant L398F in Saccharomyces cerevisiae strain INVSc1
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expression of wild-type and mutant enzymes in erg1-knockout strain KLN1
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gene ERG1, subcloning in Escherichi acoli strain DH5alpha
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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
methyl jasmonate treatment suppresses PgSQE2 mRNA expression
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mRNA expression of squalene epoxidase is associated with ER+ 7p+/8q+ breast cancer (mRNA analysis of tumor patients)
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single-copy gene, DNA and amino acid sequence determination and analysis, expression in and complementation of erg1-disrupted Saccharomyces cerevisiae mutant strain KLN1
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
enzyme expression is upregulated in hepatocellular carcinoma tissues
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overexpression of the squalene synthase 1 gene in the sense orientation increases the mRNA accumulation of downstream genes such as squalene epoxidase. Methyl jasmonate treatment of wild type roots enhances the expression of the enzyme
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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
D407F
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site-directed mutagenesis, mutant shows 8% of wild-type activity
F203A
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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
K399W/R400W/D407W
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site-directed mutagenesis, inactive mutant
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
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
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
Renatured/COMMENTARY
ORGANISM
UNIPROT
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
COMMENTARY hide
LITERATURE
biotechnology
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