Information on EC 5.4.99.17 - squalene-hopene cyclase

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The expected taxonomic range for this enzyme is: Bacteria

EC NUMBER
COMMENTARY
5.4.99.17
-
RECOMMENDED NAME
GeneOntology No.
squalene-hopene cyclase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
squalene + H2O = hopan-22-ol
show the reaction diagram
-
-
-
-
squalene = hop-22(29)-ene
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
cyclization
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
diploterol and cycloartenol biosynthesis
-
hopanoid biosynthesis (bacteria)
-
Sesquiterpenoid and triterpenoid biosynthesis
-
SYSTEMATIC NAME
IUBMB Comments
squalene mutase (cyclizing)
The enzyme also produces the cyclization product hopan-22-ol by addition of water (cf. EC 4.2.1.129, squalenehopanol cyclase). Hopene and hopanol are formed at a constant ratio of 5:1.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
cyclase, squalene-hopanoid
-
-
-
-
SHC
-
-
-
-
Spterp25
B1PT66
-
squalene-hopene cyclase
-
-
CAS REGISTRY NUMBER
COMMENTARY
76600-69-6
-
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(3S)-2,3-oxidosqualene
lanosterol
show the reaction diagram
-
-
-
-
?
(E,E,E,E)-2,6,10,14,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene
8-(4,8-Dimethyl-nona-3,7-dienyl)-1,1,4a,8a-tetramethyl-7-methylene-tetradecahydro-phenanthrene
show the reaction diagram
-
-
low conversion, NMR spectroscopic analysis
-
?
(E,E,E,E)-2,6,10,15,18,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene
1,1,4a,10a,10b-Pentamethyl-8-methylene-7-(4-methyl-pent-3-enyl)-octadecahydro-chrysene
show the reaction diagram
-
-
one of the three major products, NMR spectroscopic analysis
-
?
(E,E,E,E)-2,6,10,15,18,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene
1,1,4a,6a,8,10a-Hexamethyl-7-(4-methyl-pent-3-enyl)-1,2,3,4,4a,4b,5,6,6a,7,8,9,10,10a,12,12a-hexadecahydro-chrysene
show the reaction diagram
-
-
one of the three major products, NMR spectroscopic analysis
-
?
(E,E,E,E)-2,6,10,15,18,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene
1,1,4a,8,10a,10b-Hexamethyl-7-(4-methyl-pent-3-enyl)-1,2,3,4,4a,4b,5,6,8,9,10,10a,10b,11,12,12a-hexadecahydro-chrysene
show the reaction diagram
-
-
one of the three major products, NMR spectroscopic analysis
-
?
(E,E,E,E)-2,6,10,15,18,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene
2,4a,4b,7,7,10a-Hexamethyl-1-(4-methyl-pent-3-enyl)-octadecahydro-chrysen-2-ol
show the reaction diagram
-
-
minor product, NMR spectroscopic analysis
-
?
(E,E,E,E)-2,6,10,15,18,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene
2-(3a,5a,5b,8,8,11a-Hexamethyl-icosahydro-cyclopenta[a]chrysen-3-yl)-propan-2-ol
show the reaction diagram
-
-
minor product, NMR spectroscopic analysis
-
?
(E,E,E,E)-2,6,10,15,18,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene
alpha-3-Isopropenyl-3a,5a,5b,8,8,11a-hexamethyl-icosahydro-cyclopenta[a]chrysene
show the reaction diagram
-
-
minor product, NMR spectroscopic analysis
-
?
(E,E,E,E)-2,6,10,15,18,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene
beta-3-Isopropenyl-3a,5a,5b,8,8,11a-hexamethyl-icosahydro-cyclopenta[a]chrysene
show the reaction diagram
-
-
minor product, NMR spectroscopic analysis
-
?
(E,E,E,E)-2,6,10,15,23-pentamethyltetracosa-2,6,10,14,18,22-hexaene
2-(5a,5b,8,8,11a-Pentamethyl-icosahydro-cyclopenta[a]chrysen-3-yl)-propan-2-ol
show the reaction diagram
-
-
one of the three major products, yield 19.8%, NMR spectroscopic analysis
-
?
(E,E,E,E)-2,6,10,15,23-pentamethyltetracosa-2,6,10,14,18,22-hexaene
3-Isopropenyl-5a,5b,8,8,11a-pentamethyl-icosahydro-cyclopenta[a]chrysene
show the reaction diagram
-
-
one of the three major products, yield 29.4%, NMR spectroscopic analysis
-
?
(E,E,E,E)-2,6,10,15,23-pentamethyltetracosa-2,6,10,14,18,22-hexaene
3-Isopropenyl-5a,5b,8,8,13b-pentamethyl-icosahydro-cyclopenta[a]chrysene
show the reaction diagram
-
-
one of the three major products, yield 34.8%, NMR spectroscopic analysis
-
?
2-(farnesyldimethylallyl)pyrrole
?
show the reaction diagram
-
-
product is a 10:1 mixture of a tricyclic and a bicyclic unnatural polyprenoid
-
?
3-(farnesyldimethylallyl)indole
?
show the reaction diagram
-
-
conversion into a 2:1 mixture of a tetracyclic and a pentacyclic product
-
?
squalene
hop-22(29)-ene
show the reaction diagram
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
-
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
-
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
-
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
-
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
B1PT66, -
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
-
products are formed in a molar ratio of hopene:hopanol, 5:1
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
-
two types of water molecules ("front water" and "back waters") are involved around the deprotonation site. The two residues of Gln262 and Pro263 probably work to keep away the isopropyl group of the hopanyl cation intermediate from the "front water molecule", that is, to place the "front water" in a favorable position, leading to the minimal production of by-products, i.e., hopanol and hop-21(22)-ene. The five residues of Thr41, Glu45, Glu93, Arg127 and Trp133, by which the hydrogen-bonded network incorporating the "back waters" is constructed, increase the polarization of the "front water" to facilitate proton elimination from the isopropyl moiety of the hopanyl cation, leading to the normal product, hop-22(29)-ene
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
Alicyclobacillus acidocaldarius 104-IA
-
products are formed in a molar ratio of hopene:hopanol, 5:1
-
-
?
squalene
hopene
show the reaction diagram
-
-
-
-
?
C33 polyprene
?
show the reaction diagram
-
the enzymatic products consist of mono-, bi-, tri-, tetra- and pentacyclic skeletons, however, hexacyclic products are not generated
-
-
?
additional information
?
-
-
mutations lead to altered product pattern
-
-
-
additional information
?
-
-
overview of cyclization products of wild type and mutant enzymes
-
-
-
additional information
?
-
-
enzyme produces a wide variety of products due to lack of specificity
-
-
-
additional information
?
-
-
(E,E,E,E)-2,6,11,14,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene: no detectable enzymatic activity
-
-
-
additional information
?
-
-
no enzymatic cyclization of 3-(geranylgeranyl)indole
-
-
-
additional information
?
-
-
no substrate: 2-(geranylgeranyl)pyrrole
-
-
-
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
hop-22(29)-ene
show the reaction diagram
-
-
-
-
?
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(18E)-29-methylidenehexanor-2,3-oxidosqualene
-
IC50 0.2 microMol, pH 6.0, 55C
-
(1E,3E,7E,11E)-15,16-epoxy-8,12,16-trimethyl-1-methylthio-1,3,7,11-heptadecatetraene
-
IC50 1 microMol, pH 6.0, 55C
-
(1E,3E,7E,11E,15E)-19,20-epoxy-7,12,16,20-tetramethyl-1-methylthio-1,3,7,11,15-heneicosapentaene
-
IC50 1.4 microMol, pH 6.0, 55C, not time-dependency up to 10fold higher concentration than IC50
-
(1Z,3E,7E,11E)-15,16-epoxy-8,12,16-trimethyl-1-methylthio-1,3,7,11-heptadecatetraene
-
IC50 4 microMol, pH 6.0, 55C
-
(1Z,3E,7E,11E,15E)-19,20-epoxy-7,12,16,20-tetramethyl-1-methylthio-1,3,7,11,15-heneicosapentaene
-
IC50 1.8 microMol, pH 6.0, 55C, not time-dependency up to 10fold higher concentration than IC50
-
(2E)-4-[4-(6-bromo-1,2-benzisothiazol-3-yl)phenoxy]-N-methyl-N-prop-2-en-1-ylbut-2-en-1-aminium
-
-
(2E)-4-[4-[(4-bromophenyl)carbonyl]phenoxy]-N-methyl-N-prop-2-en-1-ylbut-2-en-1-aminium
-
-
(2E)-4-[[3-(4-bromophenyl)-1,2-benzisoxazol-6-yl]oxy]-N-methyl-N-prop-2-en-1-ylbut-2-en-1-aminium
-
-
(2E)-4-[[3-(4-bromophenyl)-1-benzofuran-6-yl]oxy]-N-methyl-N-prop-2-en-1-ylbut-2-en-1-aminium
-
-
(2E)-4-[[3-(4-bromophenyl)-1-benzothiophen-6-yl]oxy]-N-methyl-N-prop-2-en-1-ylbut-2-en-1-aminium
-
-
(3E,7E,11E)-15,16-epoxy-8,12,16-trimethyl-1-phenylthio-1,3,7,11-heptadecatetraene
-
IC50 2.2 microMol, pH 6.0, 55C
-
(4-(2-[(allyl-cyclopropyl-amino)-methyl]-cyclopropylmethoxy)-phenyl)-(4-bromo-phenyl)-methanone
-
IC50 59 nM
(4-bromo-phenyl)-(4-(2-[(cyclopropyl-methyl-amino)-methyl]-cyclopropylmethoxy)-2-fluoro-phenyl)-methanone
-
IC50 50 nM
(4-bromo-phenyl)-(4-(2-[(cyclopropyl-methyl-amino)-methyl]-cyclopropylmethoxy)-phenyl)-methanone
-
IC50 62 nM
(4-bromo-phenyl)-(4-[4-(cyclopropyl-methyl-amino)-but-2-enyloxy]-phenyl)-methanone
-
IC50 18 nM
(4-bromo-phenyl)-(4-[6-(cyclopropyl-methyl-amino)-hexyloxy]-2-fluoro-phenyl)-methanone
-
IC50 38 nM
(4-chloro-phenyl)-(4-[4-(4,5-dihydro-oxazol-2-yl)-benzylidene]-piperidin-1-yl)-methanone
-
IC50 2800 nM
(4-[6-(allyl-methyl-amino)-hexyloxy]-2-fluoro-phenyl)-(4-bromo-phenyl)-methanone
-
IC50 60 nM
(4-[6-(allyl-methyl-amino)-hexyloxy]-phenyl)-(4-bromo-phenyl)-methanone
-
IC50 96 nM
(5-hydroxycarvacryl)trimethylammonium chloride 1-piperidine carboxylate
-
i.e. AMO 1618, competitive inhibition
(5-hydroxycarvacryl)trimethylammonium chloride 1-piperidine carboxylate
-
99% inhibition at 1 mM
(5E,9E)-13,14-epoxy-6,10,14-trimethyl-1-phenylthio-1,5,9-pentadecatriene
-
IC50 7 microMol, pH 6.0, 55C
-
(5E,9E,13E)-17,18-epoxy-5,10,14,18-tetramethyl-1-phenylthio-1,5,9,13-nonadecatetraene
-
IC50 3 microMol, pH 6.0, 55C
-
1-(4-(4-[(4-chloro-phenoxycarbonyl)-methyl-amino]-cyclohexyl)-benzyl)-1-hydroxy-piperidinium
-
IC50 123 nM
1-[(4-chlorophenyl)carbonyl]-4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methylidene]piperidine
-
-
1-[4-(trans-4-[[(4-chlorophenoxy)carbonyl](methyl)amino]cyclohexyl)benzyl]piperidinium
-
-
3-(10'-(allylmethylamino)decanoyl)chroman-2,4-dione
-
IC50 100 microMol
-
3-carboxy-4-nitrophenyl-dithio-1,1',2-trisnorsqualene
-
covalently modifies C435
4'-[4-(allyl-methyl-amino)-but-2-enyloxy]-biphenyl-4-yl-(4-bromo-phenyl)-methanone
-
IC50 29 nM
4-chlorophenyl methyl(trans-4-[4-[(1-oxidopiperidin-1-yl)methyl]phenyl]cyclohexyl)carbamate
-
-
4-[4-(allyl-methyl-amino)-but-2-enyloxy]-phenyl-(4-bromo-phenyl)-methanone
-
IC50 40 nM
4-[6-(allyl-methyl-amino)-hexyloxy]-piperidin-1-yl-(4-fluoro-phenyl)-methanone
-
IC50 1200 nM
4-[6-(cyclopropyl-methyl-amino)-hexyloxy]-piperidin-1-yl-(4-fluoro-phenyl)-methanone
-
IC50 760 nM
6-([1-[(4-fluorophenyl)carbonyl]piperidin-4-yl]oxy)-N-methyl-N-prop-2-en-1-ylhexan-1-aminium
-
-
6-[(1,3-dimethyl-1H-indazol-5-yl)oxy]-N-methyl-N-prop-2-en-1-ylhexan-1-aminium
-
-
6-[4-(6-bromo-1,2-benzisothiazol-3-yl)phenoxy]-N-methyl-N-prop-2-en-1-ylhexan-1-aminium
-
-
6-[4-[(4-bromophenyl)carbonyl]-3-fluorophenoxy]-N-methyl-N-prop-2-en-1-ylhexan-1-aminium
-
-
6-[4-[(4-bromophenyl)carbonyl]phenoxy]-N-(3-hydroxypropyl)-N-methylhexan-1-aminium
-
-
6-[4-[(4-bromophenyl)carbonyl]phenoxy]-N-methyl-N-prop-2-en-1-ylhexan-1-aminium
-
-
6-[[1-(4-bromophenyl)isoquinolin-6-yl]oxy]-N-methyl-N-prop-2-en-1-ylhexan-1-aminium
-
-
6-[[3-(4-bromophenyl)-1,2-benzisothiazol-5-yl]oxy]-N-methyl-N-prop-2-en-1-ylhexan-1-aminium
-
-
6-[[3-(4-bromophenyl)-1,2-benzisoxazol-6-yl]oxy]-N-methyl-N-prop-2-en-1-ylhexan-1-amine
-
-
6-[[3-(4-bromophenyl)-1,2-benzisoxazol-6-yl]oxy]-N-methyl-N-prop-2-en-1-ylhexan-1-aminium
-
-
6-[[3-(4-bromophenyl)-1-benzofuran-6-yl]oxy]-N-methyl-N-prop-2-en-1-ylhexan-1-amine
-
-
6-[[3-(4-bromophenyl)-1-benzofuran-6-yl]oxy]-N-methyl-N-prop-2-en-1-ylhexan-1-aminium
-
-
6-[[3-(4-bromophenyl)-1-methyl-1H-indol-6-yl]oxy]-N-methyl-N-prop-2-en-1-ylhexan-1-amine
-
-
6-[[3-(4-bromophenyl)-1H-indazol-6-yl]oxy]-N-methyl-N-prop-2-en-1-ylhexan-1-amine
-
-
6-[[3-(4-bromophenyl)-1H-indazol-6-yl]oxy]-N-methyl-N-prop-2-en-1-ylhexan-1-aminium
-
-
6-[[4-(4-bromophenyl)-1H-2,3-benzoxazin-7-yl]oxy]-N-methyl-N-prop-2-en-1-ylhexan-1-aminium
-
-
7-(10'-(dimethylamino-N-decyloxy))chromen-2-one
-
IC50 5 microMol
-
7-(10-(allylmethylamino)-decyloxy)chromen-2-one
-
IC50 2 microMol
-
7-(4'-(N,N,N'-trimethylethylethylendiamino)-but-2-ynyloxy)chromen-2-one
-
not active at 100 microMol
-
7-(4'-(N-diethylamino)-but-2-ynyloxy)chromen-2-one
-
IC50 5 microMol
-
7-(4'-(N-pyrrolidyn)-but-2-ynyloxy)chromen-2-one
-
IC50 5 microMol
-
7-(4'-allylmethylamino-but-2-ynyloxy)chromen-2-one
-
IC50 0.75 microMol
-
7-(6'-(benzylamino-hexyloxy))chromen-2-one
-
IC50 8 microMol
-
7-(6-(allylmethylamino)-hexyloxy)chromen-2-one
-
IC50 4-5 microMol
-
7-(8'-(dimethylamino-N-octyloxy))chromen-2-one
-
IC50 5-7 microMol
-
7-(morpholinyl-N-hexyloxy)chromen-2-one
-
IC50 6 microMol
-
7-(morpholinyl-N-octyloxy)chromen-2-one
-
IC50 7 microMol
-
7-(piperidinyl-N-hexyloxy)chromen-2-one
-
IC50 8 microMol
-
allyl-(4-[3-(4-bromo-phenyl)-5-fluoro-1-methyl-1H-indazol-6-yloxy]-but-2-enyl)-methyl-amine
-
IC50 281 nM; IC50 332 nM
allyl-(4-[3-(4-bromo-phenyl)-benzofuran-6-yloxy]-but-2-enyl)-methyl-amine
-
IC50 23 nM
allyl-(4-[3-(4-bromo-phenyl)-benzo[b]thiophen-6-yloxy]-butyl)-methyl-amine
-
IC50 75 nM
allyl-(4-[3-(4-bromo-phenyl)-benzo[d]isoxazol-6-yloxy]-but-2-enyl)-amine
-
IC50 49 nM
allyl-(4-[4-(6-bromo-benzo[d]isothiazol-3-yl)-phenoxy]-but-2-enyl)-methyl-amine
-
IC50 130 nM
allyl-(6-[1-(4-bromo-phenyl)-isoquinolin-6-yloxy]-hexyl)-methyl-amine
-
IC50 186 nM
allyl-(6-[3-(4-bromo-phenyl)-1-methyl-1H-indazol-6-yloxy]-hexyl)-methyl-amine
-
IC50 289 nM
allyl-(6-[3-(4-bromo-phenyl)-1H-indazol-6-yloxy]-hexyl)-methyl-amine
-
IC50 180 nM
allyl-(6-[3-(4-bromo-phenyl)-benzofuran-6-yloxy]-hexyl)-methyl-amine
-
IC50 80 nM
allyl-(6-[3-(4-bromo-phenyl)-benzo[d]isothiazol-6-yloxy]-hexyl)-methyl-amine
-
IC50 306 nM
allyl-(6-[3-(4-bromo-phenyl)-benzo[d]isoxazol-6-yloxy]-hexyl)-methyl-amine
-
IC50 75 nM
allyl-(6-[4-(4-bromo-phenyl)-1H-benzo[d][1,2]oxazin-7-yloxy]-hexyl)-methyl-amine
-
IC50 172 nM
allyl-(6-[4-(6-bromo-benzo[d]isothiazol-3-yl)-phenoxy]-hexyl)-methyl-amine
-
IC50 141 nM
azasqualene
-
inhibition at 0.001 mM
-
Cu2+
-
slight inhibition at 1 mM
diethyldicarbonate
-
92% inhibition at 5 mM
dodecyldimethylamine N-oxide
-
competitive inhibition
dodecyltrimethylammonium bromide
-
competitive inhibition, 50% inhibition at 0.0001 mM
Farnesol
-
inhibition at 0.1 mM
Fe2+
-
slight inhibition at 1 mM
-
HECAMEG
-
80% inactivation compared to CHAPS
N,N-dimethyldodecylamine N-oxide
-
forms a complex with the enzyme
N-(6-[4-[(4-bromophenyl)carbonyl]-3-fluorophenoxy]hexyl)-N-methylcyclopropanaminium
-
-
N-([4'-[(4-bromophenyl)carbonyl]biphenyl-4-yl]methyl)-N-methylprop-2-en-1-aminium
-
-
N-dodecyliodoacetamide
-
IC50 wild-type >200 microMol, quintuple mutant >200 microMol, sextuple mutant >200 microMol, pH 6.0, 50C
-
N-ethylmaleimide
-
65% inhibition at 5 mM, 20% inhibition at 1 mM
N-squalenyliodoacetamide
-
IC50 wild-type >200 microMol, quintuple mutant >200 microMol, sextuple mutant 50 microMol, pH 6.0, 50C
-
N-[(2E)-4-[4-[(4-bromophenyl)carbonyl]phenoxy]but-2-en-1-yl]-N-methylcyclopropanaminium
-
-
N-[6-([1-[(4-fluorophenyl)carbonyl]piperidin-4-yl]oxy)hexyl]-N-methylcyclopropanaminium
-
-
N-[[(1S,2S)-2-([4-[(4-bromophenyl)carbonyl]-3-fluorophenoxy]methyl)cyclopropyl]methyl]-N-methylcyclopropanaminium
-
-
N-[[(1S,2S)-2-([4-[(4-bromophenyl)carbonyl]phenoxy]methyl)cyclopropyl]methyl]-N-methylcyclopropanaminium
-
-
N-[[(1S,2S)-2-([4-[(4-bromophenyl)carbonyl]phenoxy]methyl)cyclopropyl]methyl]-N-prop-2-en-1-ylcyclopropanaminium
-
-
octylthiogucopyranoside
-
complete inactivation
p-chloromercuribenzenesulfonic acid
-
96% inhibition at 1 mM
Ro 48-8071
-
IC50 0.35 microMol
sodium dodecylsulfate
-
strong inhibition
sodium taurodeoxycholate
-
under 0.15% and above 0.25%
squalene-maleimide
-
time-dependent inhibitor
taurodeoxycholate
-
80% inactivation compared to CHAPS
Triton-X100
-
96% inhibition
Zn2+
-
slight inhibition at 5 mM
Zwittergent
-
80% inactivation compared to CHAPS
-
methyl-[4-(4-piperidin-1-ylmethyl-phenyl)-cyclohexyl]-carbamic acid 4-chloro-phenyl ester
-
IC50 406 nM
additional information
-
vinyl sulfide and ketene dithioacetal derivates of truncated 2,3-ocidosqualene interact with active site of the enzyme
-
additional information
-
sulfur-substituted oxidosqualene analogues serve as inhibitors
-
additional information
-
effect of thiol-modifying inhibitors on mutant enzymes
-
additional information
-
inhibition by n-alkyldimethylammoniumhalides with alkyl chain lengths between 12 and 18 C atoms, inhibition increases with decreasing chain length
-
additional information
-
several detergents have inhibitory effect
-
additional information
-
sulfur-containing analogues of 2,3-oxidosqualene inhibit enzyme activity, 50% inhibition at concentrations in the nanomolar range
-
additional information
-
inhibitors designed as cholesterol-lowering agents, for 11 inhibitors the structures of the enzyme-inhibitor complexes were determined by X-ray crystallography
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
ethanol
-
1.6fold increase of activity when added to the enzyme test system at a concentration of 6%
Propanol
-
1.6fold increase of activity when added to the enzyme test system at a concentration of 6%
sodium taurodeoxycholate
-
1.5fold activation at 0.16%
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.001
-
(3S)-2,3-oxidosqualene
-
quintuple mutant, 50C, pH 6.0
0.0015
-
(3S)-2,3-oxidosqualene
-
wild-type, 50C, pH 6.0
0.01
-
squalene
-
quintuple mutant, 50C, pH 6.0
0.0132
-
squalene
-
wild-type, 50C, pH 6.0
0.0154
-
squalene
-
wild-type, pH 6.0, 40C
0.0162
-
squalene
-
pH 6.0, 45C, wild-type enzyme; wild-type, 45C, pH 6.0
0.0167
-
squalene
-
mutant T41A, 45C, pH 6.0; pH 6.0, 45C, mutant T41A
0.0169
-
squalene
-
mutant W133A, 45C, pH 6.0; pH 6.0, 45C, mutant W133A
0.017
-
squalene
-
wild type enzyme and D376E mutant
0.0189
-
squalene
-
mutant E93A, 45C, pH 6.0; pH 6.0, 45C, mutant E93A
0.0213
-
squalene
-
mutant E45A, 45C, pH 6.0; pH 6.0, 45C, mutant E45A
0.0242
-
squalene
-
wild-type, pH 6.0, 50C
0.0255
-
squalene
-
mutant R127Q, 45C, pH 6.0; pH 6.0, 45C, mutant R127Q
0.0279
-
squalene
-
mutant F605 changed to fluorophenylalanine plus mutation Y606A, pH 6.0, 50C
0.0324
-
squalene
-
mutant F605 changed to difluorophenylalanine plus mutation Y606A, pH 6.0, 50C
0.0352
-
squalene
-
mutant F365 changed to fluorophenylalanine, pH 6.0, 50C
0.0416
-
squalene
-
mutant F365 changed to difluorophenylalanine, pH 6.0, 50C
0.0479
-
squalene
-
mutant F6365 changed to trifluorophenylalanine, pH 6.0, 50C
0.0525
-
squalene
-
mutant F605Y, pH 6.0, 40C
0.0816
-
squalene
-
pH 6.0, 45C, mutant F434A
0.0955
-
squalene
-
pH 6.0, 45C, mutant F437A
0.102
-
squalene
-
mutant Q262A, 45C, pH 6.0; pH 6.0, 45C, mutant Q262A
0.104
-
squalene
-
mutant F605Y, pH 6.0, 50C
0.105
-
squalene
-
mutant F605 changed to O-methyltyrosine, pH 6.0, 40C
0.118
-
squalene
-
mutant F605W, pH 6.0, 40C
0.13
-
squalene
-
mutant F365Y, pH 6.0, 50C
0.152
-
squalene
-
mutant F605Y changed to O-methyltyrosine, pH 6.0, 50C
0.156
-
squalene
-
mutant Q262G, 45C, pH 6.0; pH 6.0, 45C, mutant Q262G
0.185
-
squalene
-
mutant P263A, 45C, pH 6.0; pH 6.0, 45C, mutant P263A
0.185
-
squalene
-
mutant F365Y changed to O-methyltyrosine, pH 6.0, 50C
0.191
-
squalene
-
mutant F605W, pH 6.0, 50C
0.197
-
squalene
-
mutantY267A, 45C, pH 6.0; pH 6.0, 45C, mutant Y267A
0.237
-
squalene
-
mutant P263G, 45C, pH 6.0; pH 6.0, 45C, mutant P263G
0.816
-
squalene
-
mutant F434A, 45C, pH 6.0
0.955
-
squalene
-
mutant F437A, 45C, pH 6.0
0.0023
-
(3S)-2,3-oxidosqualene
-
sextuple mutant, 50C, pH 6.0
additional information
-
additional information
-
Km for wild type and mutant enzymes
-
additional information
-
additional information
-
squalene sextuple mutant: no activity
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.15
-
squalene
-
mutant F365Y changed to O-methyltyrosine, pH 6.0, 50C
0.17
-
squalene
-
mutant F365Y, pH 6.0, 50C
0.25
-
squalene
-
wild-type, pH 6.0, 40C
0.27
-
squalene
-
mutant F605Y, pH 6.0, 40C
0.31
-
squalene
-
mutant F605W, pH 6.0, 40C
0.345
-
squalene
-
pH 6.0, 45C, mutant E45A
0.353
-
squalene
-
pH 6.0, 45C, mutant E93A
0.448
-
squalene
-
pH 6.0, 45C, mutant R127Q
0.45
-
squalene
-
mutant F605 changed to O-methyltyrosine, pH 6.0, 40C
0.54
-
squalene
-
pH 6.0, 45C, mutant F434A
0.54
-
squalene
-
mutant F605 changed to difluorophenylalanine plus mutation Y606A, pH 6.0, 50C
0.62
-
squalene
-
pH 6.0, 45C, mutant W133A
0.64
-
squalene
-
pH 6.0, 45C, mutant Y267A
0.7
-
squalene
-
mutant F605Y changed to O-methyltyrosine, pH 6.0, 50C
0.735
-
squalene
-
pH 6.0, 45C, mutant T41A
0.75
-
squalene
-
mutant F6365 changed to trifluorophenylalanine, pH 6.0, 50C
0.82
-
squalene
-
mutant F605 changed to fluorophenylalanine plus mutation Y606A, pH 6.0, 50C
0.86
-
squalene
-
pH 6.0, 45C, wild-type enzyme
0.92
-
squalene
-
mutant F365 changed to difluorophenylalanine, pH 6.0, 50C
1.03
-
squalene
-
pH 6.0, 45C, mutant F437A
1.06
-
squalene
-
pH 6.0, 45C, mutant P263G
1.09
-
squalene
-
pH 6.0, 45C, mutant P263A
1.1
-
squalene
-
mutant F365 changed to fluorophenylalanine, pH 6.0, 50C
1.21
-
squalene
-
pH 6.0, 45C, mutant Q262A
1.32
-
squalene
-
mutant F605W, pH 6.0, 50C
1.37
-
squalene
-
pH 6.0, 45C, mutant Q262G
1.82
-
squalene
-
mutant F605Y, pH 6.0, 50C
1.98
-
squalene
-
wild-type, pH 6.0, 50C
additional information
-
additional information
-
wild type and mutant enzymes
-
kcat/KM VALUE [1/mMs-1]
kcat/KM VALUE [1/mMs-1] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
3.2
-
squalene
-
pH 6.0, 45C, mutant Y267A
16696
4.5
-
squalene
-
pH 6.0, 45C, mutant P263G
16696
5.9
-
squalene
-
pH 6.0, 45C, mutant P263A
16696
6.6
-
squalene
-
pH 6.0, 45C, mutant F434A
16696
8.8
-
squalene
-
pH 6.0, 45C, mutant Q262G
16696
10.8
-
squalene
-
pH 6.0, 45C, mutant F437A
16696
11.9
-
squalene
-
pH 6.0, 45C, mutant Q262A
16696
16.1
-
squalene
-
pH 6.0, 45C, mutant E45A
16696
17.6
-
squalene
-
pH 6.0, 45C, mutant R127Q
16696
18.7
-
squalene
-
pH 6.0, 45C, mutant E93A
16696
36.7
-
squalene
-
pH 6.0, 45C, mutant W133A
16696
44
-
squalene
-
pH 6.0, 45C, mutant T41A
16696
53.09
-
squalene
-
pH 6.0, 45C, wild-type enzyme
16696
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.00054
-
(5-hydroxycarvacryl)trimethylammonium chloride 1-piperidine carboxylate
-
-
0.00014
-
dodecyldimethylamine N-oxide
-
-
0.00032
-
dodecyltrimethylammonium bromide
-
-
additional information
-
additional information
-
Ki for sulfur-substituted oxidosqualene analogues
-
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0002
-
(18E)-29-methylidenehexanor-2,3-oxidosqualene
-
IC50 0.2 microMol, pH 6.0, 55C
-
0.001
-
(1E,3E,7E,11E)-15,16-epoxy-8,12,16-trimethyl-1-methylthio-1,3,7,11-heptadecatetraene
-
IC50 1 microMol, pH 6.0, 55C
-
0.0014
-
(1E,3E,7E,11E,15E)-19,20-epoxy-7,12,16,20-tetramethyl-1-methylthio-1,3,7,11,15-heneicosapentaene
-
IC50 1.4 microMol, pH 6.0, 55C, not time-dependency up to 10fold higher concentration than IC50
-
0.004
-
(1Z,3E,7E,11E)-15,16-epoxy-8,12,16-trimethyl-1-methylthio-1,3,7,11-heptadecatetraene
-
IC50 4 microMol, pH 6.0, 55C
-
0.0018
-
(1Z,3E,7E,11E,15E)-19,20-epoxy-7,12,16,20-tetramethyl-1-methylthio-1,3,7,11,15-heneicosapentaene
-
IC50 1.8 microMol, pH 6.0, 55C, not time-dependency up to 10fold higher concentration than IC50
-
0.0022
-
(3E,7E,11E)-15,16-epoxy-8,12,16-trimethyl-1-phenylthio-1,3,7,11-heptadecatetraene
-
IC50 2.2 microMol, pH 6.0, 55C
-
0.000059
-
(4-(2-[(allyl-cyclopropyl-amino)-methyl]-cyclopropylmethoxy)-phenyl)-(4-bromo-phenyl)-methanone
-
IC50 59 nM
0.00005
-
(4-bromo-phenyl)-(4-(2-[(cyclopropyl-methyl-amino)-methyl]-cyclopropylmethoxy)-2-fluoro-phenyl)-methanone
-
IC50 50 nM
0.000062
-
(4-bromo-phenyl)-(4-(2-[(cyclopropyl-methyl-amino)-methyl]-cyclopropylmethoxy)-phenyl)-methanone
-
IC50 62 nM
0.000018
-
(4-bromo-phenyl)-(4-[4-(cyclopropyl-methyl-amino)-but-2-enyloxy]-phenyl)-methanone
-
IC50 18 nM
0.000038
-
(4-bromo-phenyl)-(4-[6-(cyclopropyl-methyl-amino)-hexyloxy]-2-fluoro-phenyl)-methanone
-
IC50 38 nM
0.0028
-
(4-chloro-phenyl)-(4-[4-(4,5-dihydro-oxazol-2-yl)-benzylidene]-piperidin-1-yl)-methanone
-
IC50 2800 nM
0.00006
-
(4-[6-(allyl-methyl-amino)-hexyloxy]-2-fluoro-phenyl)-(4-bromo-phenyl)-methanone
-
IC50 60 nM
0.000096
-
(4-[6-(allyl-methyl-amino)-hexyloxy]-phenyl)-(4-bromo-phenyl)-methanone
-
IC50 96 nM
0.007
-
(5E,9E)-13,14-epoxy-6,10,14-trimethyl-1-phenylthio-1,5,9-pentadecatriene
-
IC50 7 microMol, pH 6.0, 55C
-
0.003
-
(5E,9E,13E)-17,18-epoxy-5,10,14,18-tetramethyl-1-phenylthio-1,5,9,13-nonadecatetraene
-
IC50 3 microMol, pH 6.0, 55C
-
0.000123
-
1-(4-(4-[(4-chloro-phenoxycarbonyl)-methyl-amino]-cyclohexyl)-benzyl)-1-hydroxy-piperidinium
-
IC50 123 nM
0.1
-
3-(10'-(allylmethylamino)decanoyl)chroman-2,4-dione
-
IC50 100 microMol
-
0.000029
-
4'-[4-(allyl-methyl-amino)-but-2-enyloxy]-biphenyl-4-yl-(4-bromo-phenyl)-methanone
-
IC50 29 nM
0.00004
-
4-[4-(allyl-methyl-amino)-but-2-enyloxy]-phenyl-(4-bromo-phenyl)-methanone
-
IC50 40 nM
0.0012
-
4-[6-(allyl-methyl-amino)-hexyloxy]-piperidin-1-yl-(4-fluoro-phenyl)-methanone
-
IC50 1200 nM
0.00076
-
4-[6-(cyclopropyl-methyl-amino)-hexyloxy]-piperidin-1-yl-(4-fluoro-phenyl)-methanone
-
IC50 760 nM
0.000075
-
6-[[3-(4-bromophenyl)-1,2-benzisoxazol-6-yl]oxy]-N-methyl-N-prop-2-en-1-ylhexan-1-amine
-
-
0.005
-
7-(10'-(dimethylamino-N-decyloxy))chromen-2-one
-
IC50 5 microMol
-
0.002
-
7-(10-(allylmethylamino)-decyloxy)chromen-2-one
-
IC50 2 microMol
-
0.005
-
7-(4'-(N-diethylamino)-but-2-ynyloxy)chromen-2-one, 7-(4'-(N-pyrrolidyn)-but-2-ynyloxy)chromen-2-one
-
IC50 5 microMol
-
0.00075
-
7-(4'-allylmethylamino-but-2-ynyloxy)chromen-2-one
-
IC50 0.75 microMol
-
0.008
-
7-(6'-(benzylamino-hexyloxy))chromen-2-one
-
IC50 8 microMol
-
0.004
0.005
7-(6-(allylmethylamino)-hexyloxy)chromen-2-one
-
IC50 4-5 microMol
-
0.005
0.007
7-(8'-(dimethylamino-N-octyloxy))chromen-2-one
-
IC50 5-7 microMol
-
0.006
-
7-(morpholinyl-N-hexyloxy)chromen-2-one
-
IC50 6 microMol
-
0.007
-
7-(morpholinyl-N-octyloxy)chromen-2-one
-
IC50 7 microMol
-
0.008
-
7-(piperidinyl-N-hexyloxy)chromen-2-one
-
IC50 8 microMol
-
0.000281
-
allyl-(4-[3-(4-bromo-phenyl)-5-fluoro-1-methyl-1H-indazol-6-yloxy]-but-2-enyl)-methyl-amine
-
IC50 281 nM
0.000332
-
allyl-(4-[3-(4-bromo-phenyl)-5-fluoro-1-methyl-1H-indazol-6-yloxy]-but-2-enyl)-methyl-amine
-
IC50 332 nM
0.000023
-
allyl-(4-[3-(4-bromo-phenyl)-benzofuran-6-yloxy]-but-2-enyl)-methyl-amine
-
IC50 23 nM
0.000075
-
allyl-(4-[3-(4-bromo-phenyl)-benzo[b]thiophen-6-yloxy]-butyl)-methyl-amine
-
IC50 75 nM
0.000049
-
allyl-(4-[3-(4-bromo-phenyl)-benzo[d]isoxazol-6-yloxy]-but-2-enyl)-amine
-
IC50 49 nM
0.00013
-
allyl-(4-[4-(6-bromo-benzo[d]isothiazol-3-yl)-phenoxy]-but-2-enyl)-methyl-amine
-
IC50 130 nM
0.000186
-
allyl-(6-[1-(4-bromo-phenyl)-isoquinolin-6-yloxy]-hexyl)-methyl-amine
-
IC50 186 nM
0.000289
-
allyl-(6-[3-(4-bromo-phenyl)-1-methyl-1H-indazol-6-yloxy]-hexyl)-methyl-amine
-
IC50 289 nM
0.00018
-
allyl-(6-[3-(4-bromo-phenyl)-1H-indazol-6-yloxy]-hexyl)-methyl-amine
-
IC50 180 nM
0.00008
-
allyl-(6-[3-(4-bromo-phenyl)-benzofuran-6-yloxy]-hexyl)-methyl-amine
-
IC50 80 nM
0.000306
-
allyl-(6-[3-(4-bromo-phenyl)-benzo[d]isothiazol-6-yloxy]-hexyl)-methyl-amine
-
IC50 306 nM
0.000075
-
allyl-(6-[3-(4-bromo-phenyl)-benzo[d]isoxazol-6-yloxy]-hexyl)-methyl-amine
-
IC50 75 nM
0.000172
-
allyl-(6-[4-(4-bromo-phenyl)-1H-benzo[d][1,2]oxazin-7-yloxy]-hexyl)-methyl-amine
-
IC50 172 nM
0.000141
-
allyl-(6-[4-(6-bromo-benzo[d]isothiazol-3-yl)-phenoxy]-hexyl)-methyl-amine
-
IC50 141 nM
0.000406
-
methyl-[4-(4-piperidin-1-ylmethyl-phenyl)-cyclohexyl]-carbamic acid 4-chloro-phenyl ester
-
IC50 406 nM
0.2
-
N-dodecyliodoacetamide
-
IC50 wild-type >200 microMol, quintuple mutant >200 microMol, sextuple mutant >200 microMol, pH 6.0, 50C
-
0.05
-
N-squalenyliodoacetamide
-
IC50 sextuple mutant 50 microMol, pH 6.0, 50C
-
0.2
-
N-squalenyliodoacetamide
-
IC50 quintuple mutant >200 microMol; IC50 wild-type >200 microMol
-
0.00035
-
Ro 48-8071
-
IC50 0.35 microMol
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.00000227
-
-
crude extract
additional information
-
-
specific activities for wild type and mutant enzymes
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.8
-
B1PT66, -
at 35-45C
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
4.8
8
-
50% activity at pH 8, very low activity at pH 4.8
5
8
-
no activity below pH 5 or above pH 8
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
35
45
B1PT66, -
at pH 6.8
45
-
-
mutant F437A; mutant F437A0
50
60
-
mutantY267A; mutant Y267A
50
-
-
mutant E45A; mutant P263A; mutant P263G; mutant P263G, mutant P263A, mutant E45A, mutant R127Q; mutant R127Q
55
-
-
mutant E93A; mutant E93A, mutant W133A; mutant W133A
60
-
-
mutant F434A; mutant T41A; wild-type; wild-type, mutant T41A, mutant F434A
additional information
-
-
wild type and mutant enzymes
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
Alicyclobacillus acidocaldarius 104-IA, Methylococcus capsulatus Bath
-
-
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
70000
-
-
SDS-PAGE
74000
-
-
calculated from amino acid sequence
92000
-
B1PT66, -
recombinant His-tagged Spterp25, SDS-PAGE
150000
-
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
dimer
-
2 * 75000, SDS-PAGE, enzyme forms aggregates in absence of detergent
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
cocrystallization with 2-azasqualene
-
complexes with 11 human oxidosqualene cyclase inhibitors produced by cocrystallization, elucidation of the structures by X-ray diffraction analyses
-
resolution of 2.0 Angstrom
-
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
60
-
-
wild type enzyme: 50% loss of activity after 120 min, D376E mutant: 50% loss of activity after 100 min
70
-
-
stable for 10 min
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-20C, stable for weeks
-
6C, stable for several days
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
ion exchange and gel filtration
-
wild type and mutants, homogeneity
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expressed in Escherichia coli
-
expression in Escherichia coli
-
expression in Escherichia coli BL21
-
expression in Escherichia coli JM 105
-
expressed in Escherichia coli BL21(DE3)pLysS cells
B1PT66, -
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
C25S/C50S/C435S/C455S/C537S
-
quintuple mutant
C25S/C50S/D376C/C435S/C455S/C537S
-
sextuple mutant
D376E
-
10% enzyme activity
D376E/D377E
-
no enzyme activity
D376G
-
0.2% activity when enzyme concentration is increased to 100fold
D376Q
-
no enzyme activity
D376R
-
no enzyme activity
D377C/V380E/V381A
-
no detectable cyclization of squalene
D377E
-
0.2% activity when enzyme concentration is increased to 100fold
D377G
-
0.2% activity when enzyme concentration is increased to 100fold
D377Q
-
0.2% activity when enzyme concentration is increased to 100fold
D377R
-
no enzyme activity
E45A
-
reduced enzyme activity
E45A
-
mutation located around the 'back waters'; production of hop-22(29)-ene is less throughout the entire temperature range than that by the wild-type. Hop-21(22)ene is not produced
E45D
-
reduced enzyme activity
E45K
-
no enzyme activity
E45Q
-
slightly increased enzyme activity
E93A
-
mutation located around the 'back waters'; production of hop-22(29)-ene is less throughout the entire temperature range than that by the wild-type. Hop-21(22)ene is not produced
F365W
-
marginal catalytic activity
F365Y
-
and mutant with F365 changed to unnatural amino acid O-methyltyrosine. Both show increased decreased activity at high temperature
F434A
-
mutation near the substrat channel; production of hop-22(29)-ene is decreased, production of hopanol is markedly increased at lower temperatures
F437A
-
mutation near the substrat channel; production of hop-22(29)-ene is decreased, production of hopanol is markedly increased at lower temperatures
F605A
-
altered product pattern
F605W
-
increased catalytic acitivy at low temperature, but decreased activity at high temperature due to higher cation-pi binding energies
F605Y
-
and mutant with F605 changed to unnatural amino acid O-methyltyrosine. Both show increased catalytic acitivy at low temperature, but decreased activity at high temperature due to higher cation-pi binding energies
P263A
-
mutation located between C29 of the hopanyl cation and the 'front water'; the mutant produces hopanol as the main product instead of hop-22(29)-ene. The mutant also produces hop-21(22)ene
P263G
-
mutation located between C29 of the hopanyl cation and the 'front water'; the mutant produces hopanol as the main product instead of hop-22(29)-ene. The mutant also produces hop-21(22)ene
Q262A
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mutation located between C29 of the hopanyl cation and the 'front water'
Q262G
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mutation located between C29 of the hopanyl cation and the 'front water'; the mutant produces hopanol as the main product instead of hop-22(29)-ene. The mutant also produces hop-21(22)ene
R127Q
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mutation located around the 'back waters'; production of hop-22(29)-ene is less throughout the entire temperature range than that by the wild-type. Hop-21(22)ene is not produced
T41A
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mutation located around the 'back waters'; production of hop-22(29)-ene is less throughout the entire temperature range than that by the wild-type. Hop-21(22)ene is not produced
W133A
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mutation located around the 'back waters'; production of hop-22(29)-ene is less throughout the entire temperature range than that by the wild-type. Hop-21(22)ene is not produced
W23V
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same activity and optimal temperature as wild type enzyme
W258L
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60% of wild type activity, lower temperature optimum
W406V
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no enzyme activity
W417A
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no enzyme activity
W485V
-
same activity and optimal temperature as wild type enzyme
W522V
-
same activity and optimal temperature as wild type enzyme
W533A
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same activity and optimal temperature as wild type enzyme
W591L
-
same activity and optimal temperature as wild type enzyme
W78S
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same activity and optimal temperature as wild type enzyme
Y267A
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mutation near the substrat channel; production of hop-22(29)-ene is decreased, production of hopanol is markedly increased at lower temperatures
Y495F
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reduced enzyme activity, wild-type product pattern
Y606A
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kinetics identical to wild-type
Y609F
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wild type activity, altered product pattern
Y612F
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reduced enzyme activity, wild-type product pattern
G262A
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the mutant produces hopanol as the main product instead of hop-22(29)-ene. The mutant also produces hop-21(22)ene
additional information
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mutations of Y609, Y495, Y612 and Y420 lead to an altered product pattern, compared to wild-type enzyme
additional information
-
overview
additional information
-
modification of critically located Cys residues
additional information
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various mutations of conserved amino acid residues
additional information
-
replacement of F605 by mono-, di- or trifluorophenylalanine, with or without additional mutation Y606A, kinetic analysis. Mutant F605 changed to trifluorophenylalanine plus mutation Y606A has negligibly small activity
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
synthesis
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production of unnatural polyprenoids and supranatural steroids by manipulation of the enzyme reaction by combination of substrate analogues