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Information on EC 5.4.99.17 - squalene-hopene cyclase and Organism(s) Alicyclobacillus acidocaldarius and UniProt Accession P33247
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EC Tree
5.4.99.17 squalene-hopene cyclaseIUBMB Comments
The enzyme also produces the cyclization product hopan-22-ol by addition of water (cf. EC 4.2.1.129, squalene-hopanol cyclase). Hopene and hopanol are formed at a constant ratio of 5:1.
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Word Map
- 5.4.99.17
-
cyclization
- alicyclobacillus
- acidocaldarius
-
hopanoids
- cyclases
- oxidosqualene
-
pentacyclic
-
triterpene
- 2,3-oxidosqualene
-
tetracyclic
- tetrahymanol
-
carbocation
-
polyolefinic
-
5.4.99.7
- lanosterol
-
aspartate-rich
- synthesis
The taxonomic range for the selected organisms is: Alicyclobacillus acidocaldarius
The expected taxonomic range for this enzyme is: Bacteria, Archaea, Eukaryota
The expected taxonomic range for this enzyme is: Bacteria, Archaea, Eukaryota
Synonyms
squalene-hopene cyclase, squalene hopene cyclase, aacshc, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
cyclase, squalene-hopanoid
-
-
-
-
SHC
SHC
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
squalene = hop-22(29)-ene
overall mechanism of the polycyclization reaction of SHCs and structures of squalene cyclization products, overview
squalene = hop-22(29)-ene
catalytic mechanism, the initial reaction catalyzed is the protonation of the terminal double bond of squalene. The conserved DXDD motif of SHCs is essential for this protonation reaction. In Alicyclobacillus acidocaldarius SHC, Asp376 of this motif is hydrogen bonded to His451, and an additional hydrogen bond exists to an ordered water molecule, which connects D376 to the hydroxyl group of the Y495 side chain and thus further enhances its acidity. The carboxyl groups of Asp374 and Asp377 accommodate the positive charge of the D376-H451 pair prior to proton transfer. After proton transfer to the 2,3-double bond of squalene, the D376-H451 pair loses its charge, leaving the remaining negative charge on the D374-D377 pair for stabilization of the initial cationic intermediates (24, 101). Reprotonation of D376 occurs through a water molecule bound to Y495-OH, which can transfer protons from disordered water in the solvent-accessible upper cavity of SHC
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
cyclization
cyclization
-
-
-
-
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, squalene-hopanol cyclase). Hopene and hopanol are formed at a constant ratio of 5:1.
CAS REGISTRY NUMBER
COMMENTARY
76600-69-6
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(S)-6,7-epoxygeraniol + H2O
(1S,3R)-3-(hydroxymethyl)-2,2-dimethyl-4-methylidenecyclohexan-1-ol
0.57% conversion with high enzyme concentrations
-
-
?
(S)-citronellal + H2O
(-)-iso-isopulegol
0.59% conversion with high enzyme concentrations
-
-
?
citronellal
isopulegol
activity of mutant Y420C, not of the wild-type enzyme
i.e. 2-isopropenyl-5-methyl-cyclohexanol
-
?
geraniol + H2O
gamma-cyclogeraniol + cyclogeraniol hydrate
0.4% conversion with high enzyme concentrations
-
-
?
(23E)-hydroxysqualene
rac-(2R)-2-((3aS,5aR,5bR,7aS,11aS,11bR)-5a,5b,8,8,11a,13b-hexamethylicosahydro-1H-cyclopenta[a]chrysen-3-yl)propanal + rac-(2R)-2-((3aR,5aS,5bS,7aR,11aR,11bS)-5a,5b,8,8,11a,13b-hexamethylicosahydro-1H-cyclopenta[a]chrysen-3-yl)propanal + rac-2-((3aR,5aS,5bS,7aR,11aR,11bS)-5a,5b,8,8,11a,13b-hexamethylicosahydro-1H-cyclopenta[a]chrysen-3-yl)prop-2-en-1-ol
-
-
-
-
?
(23E)-methylsqualene
rac-(5R,9S,10R,13R,14R,17S)-4,4,10,13,14-pentamethyl-17-((E)-6-methyloct-5-en-2-yl)-2,3,4,5,6,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene + rac-(5R,8S,9S,10R,13S,14S)-4,4,8,10,14-pentamethyl-17-((E)-6-methylocta-1,5-dien-2-yl)hexadecahydro-1H-cyclopenta[a]phenanthrene + rac-(3aR,5aS,5bS,7aR,11aR,11bS,13aS)-3-(but-1-en-2-yl)-5a,5b,8,8,11a,13b-hexamethylicosahydro-1H-cyclopenta[a]chrysene + rac-2-((3aR,5aS,5bS,7aR,11aR,11bS,13aS)-5a,5b,8,8,11a,13b-hexamethylicosahydro-1H-cyclopenta[a]chrysen-3-yl)butan-2-ol
-
-
-
-
?
(23Z)-hydroxysqualene
rac-(2R)-2-((3aS,5aR,5bR,7aS,11aS,11bR)-5a,5b,8,8,11a,13b-hexamethylicosahydro-1H-cyclopenta[a]chrysen-3-yl)propanal + rac-(2R)-2-((3aR,5aS,5bS,7aR,11aR,11bS)-5a,5b,8,8,11a,13b-hexamethylicosahydro-1H-cyclopenta[a]chrysen-3-yl)propanal + rac-2-((3aR,5aS,5bS,7aR,11aR,11bS)-5a,5b,8,8,11a,13b-hexamethylicosahydro-1H-cyclopenta[a]chrysen-3-yl)prop-2-en-1-ol + ((9beta,10alpha,13xi,20xi)-20,26-epoxydammar-24-ene)
-
-
-
-
?
(23Z)-methylsqualene
(23Z)-methylsqualene + rac-(3aR,5aS,5bS,7aR,11aR,11bS,13aS)-3-(but-1-en-2-yl)-5a,5b,8,8,11a,13b-hexamethylicosahydro-1H-cyclopenta[a]chrysene + rac-(3aR,5aS,5bS,7aR,11aR,11bS)-3-((E)-but-2-en-2-yl)-5a,5b,8,8,11a,13b-hexamethylicosahydro-1H-cyclopenta[a]chrysene
-
-
-
-
?
(2E)-methylsqualene
rac-(3aR,5aS,5bS,7aR,11aR,11bS,13aS)-8-ethyl-5a,5b,8,11a,13b-pentamethyl-3-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysene
-
-
-
-
?
(6E)-3,7,11-trimethyldodeca-1,6,10-trien-3-ol
(-)-caparrapioxide + (-)-8-epi-caparrapioxide
-
-
-
-
?
(6E,10E)-2,6,10-trimethyldodeca-2,6,10-triene
(4aR,5S,8aS)-1,1,4a,5,6-pentamethyl-1,2,3,4,4a,5,8,8a-octahydronaphthalene + (4aR,5S,8aS)-1,1,4a,5-tetramethyl-6-methylidenedecahydronaphthalene + (1R,2R,4aS,8aS)-1,2,5,5,8a-pentamethyldecahydronaphthalen-2-ol + (1R,2S,4aS,8aS)-1,2,5,5,8a-pentamethyldecahydronaphthalen-2-ol + (4aS,8aS)-4,4,7,8,8a-pentamethyl-1,2,3,4,4a,5,6,8a-octahydronaphthalene + (3S,4aS,8aS)-3,4,4,8,8a-pentamethyl-1,2,3,4,4a,5,6,8a-octahydronaphthalene
-
via bicyclic C8-cation
-
-
?
(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
-
-
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
-
-
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
-
-
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
-
-
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
-
-
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
-
-
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
-
-
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
-
-
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
-
-
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
-
-
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
-
-
one of the three major products, yield 34.8%, NMR spectroscopic analysis
-
?
(R)-citronellal + H2O
(-)-isopulegol + (+)-neoiso-isopulegol
-
-
-
-
?
10-ethylsqualene
(2R)-2-[(7E,11E)-3-ethyl-8,12,16-trimethylheptadeca-7,11,15-trien-1-yl]-1,1-dimethyl-3-methylidenecyclohexane + (3R,5aR,9aS)-3-[(5Z)-6,10-dimethylundeca-5,9-dien-2-yl]-3-ethyl-6,6,9a-trimethyl-2,3,5,5a,6,7,8,9,9a,9b-decahydro-1H-cyclopenta[a]naphthalene + (4aS,5R,8aR)-6-ethylidene-1,1,4a-trimethyl-5-[(3E,7E)-4,8,12-trimethyltrideca-3,7,11-trien-1-yl]decahydronaphthalene + (4aR,5S,8aR)-6-ethyl-1,1,4a-trimethyl-5-[(3E,7E)-4,8,12-trimethyltrideca-3,7,11-trien-1-yl]decahydronaphthalene + (2R)-2-[(3E,7E,11E)-3-ethyl-8,12,16-trimethylheptadeca-3,7,11,15-tetraen-1-yl]-1,3,3-trimethylcyclohexanol
-
-
-
-
?
15-ethylsqualene
(2R)-2-[(3E,11E)-8-ethyl-3,12,16-trimethylheptadeca-3,7,11,15-tetraen-1-yl]-1,1-dimethyl-3-methylidenecyclohexane + (4aS,5S,8aR)-5-[(7E)-4-ethyl-8,12-dimethyltrideca-3,7,11-trien-1-yl]-1,1,4a-trimethyl-6-methylidenedecahydronaphthalene + (4aS,5S,8aR)-5-[(7E)-4-ethyl-8,12-dimethyltrideca-3,7,11-trien-1-yl]-1,1,4a,6-tetramethyl-1,2,3,4,4a,5,8,8a-octahydronaphthalene + (2R)-2-[(3E,11E)-8-ethyl-3,12,16-trimethylheptadeca-3,7,11,15-tetraen-1-yl]-1,3,3-trimethylcyclohexanol
-
-
-
-
?
19-ethylsqualene
(2R)-2-[(3E,7E,11E)-12-ethyl-3,8,16-trimethylheptadeca-3,7,11,15-tetraen-1-yl]-1,1-dimethyl-3-methylidenecyclohexane + (6R)-6-[(3E,7E,11E)-12-ethyl-3,8,16-trimethylheptadeca-3,7,11,15-tetraen-1-yl]-1,5,6-trimethylcyclohexene + (4aS,5S,8aR)-5-[(3E,7E)-8-ethyl-4,12-dimethyltrideca-3,7,11-trien-1-yl]-1,1,4a-trimethyl-6-methylidenedecahydronaphthalene + (5R,8R,9R,10S,14S)-4,4,8,10,14-pentamethyl-17-(7-methyloct-6-en-3-yl)-2,3,4,5,6,7,8,9,10,11,12,14,15,16-tetradecahydro-1H-cyclopenta[a]phenanthrene + (4aS,5S,8aR)-5-[(3E,7E)-9-ethyl-4,12-dimethyltrideca-3,7,11-trien-1-yl]-1,1,4a,6-tetramethyl-1,2,3,4,4a,5,8,8a-octahydronaphthalene + (3S,3aS,5aR,5bR,7aR,11aS,11bS,13aR,13bS)-13b-ethyl-5a,5b,8,8,11a-pentamethyl-3-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysene
-
-
-
-
?
2-((2E,6E)-3,7,11-trimethyldodeca-2,6,10-trienyl)phenol + H2O
(3S,4aR,6aR,12aR,12bS)-4,4,6a,12b-tetramethyl-1,3,4,4a,5,6,6a,12,12a,12b-decahydro-2H-benzo[a]xanthen-3-ol + 2 H+
-
-
-
-
?
2-((2E,6E)-9-(3,3-dimethyloxiran-2-yl)-3,7-dimethylnona-2,6-dienyl)phenol
(4aS,6aR,12aR,12bS)-4,4,6a,12b-tetramethyl-1,3,4,4a,5,6,6a,12,12a,12b-decahydro-2H-benzo[a]xanthene + 2-[[(1S,4aS,8aS)-2,5,5,8a-tetramethyl-1,4,4a,5,6,7,8,8a-octahydronaphthalen-1-yl]methyl]phenol + 2-[[(1S,4aS,8aS)-5,5,8a-trimethyl-2-methylidenedecahydronaphthalen-1-yl]methyl]phenol
-
-
-
-
?
2-(farnesyldimethylallyl)pyrrole
?
-
-
product is a 10:1 mixture of a tricyclic and a bicyclic unnatural polyprenoid
-
?
3-(farnesyldimethylallyl)indole
?
-
-
conversion into a 2:1 mixture of a tetracyclic and a pentacyclic product
-
?
C33 polyprene
?
-
the enzymatic products consist of mono-, bi-, tri-, tetra- and pentacyclic skeletons, however, hexacyclic products are not generated
-
-
?
citronellal
isopulegol
-
-
i.e. 2-isopropenyl-5-methyl-cyclohexanol
-
?
farnesol
drimenol + albicanol + driman-8,11-diol + [(1S,2R,8aS)-2,5,5,8a-tetramethyl-2-[[(2E,6E)-3,7,11-trimethyldodeca-2,6,10-trien-1-yl]oxy]decahydronaphthalen-1-yl]methanol
-
-
drimane-type sequiterpenes
-
?
geranylacetone
(8aS)-2,5,5,8a-tetramethyl-4a,5,6,7,8,8a-hexahydro-4H-chromene
-
-
-
-
?
squalene
hop-22(29)-ene + hopanol
-
the enzyme catalyzes cyclization of the linear triterpenoid squalene to hopene and hopanol by the class II mechanism
-
-
?
squalene + H2O
hopan-22-ol
-
-
-
-
?
squalene
hop-22(29)-ene
-
-
-
-
?
squalene
hop-22(29)-ene
-
-
-
-
?
squalene
hop-22(29)-ene
-
-
the enzyme from Alicyclobacillus acidocaldarius yields pentacyclic hopene and hopanol (diplopterol) via a hopanyl cation from squalene
-
?
squalene
hop-22(29)-ene
-
products are formed in a molar ratio of hopene:hopanol, 5:1
-
-
?
squalene
hop-22(29)-ene
-
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
-
-
?
additional information
?
-
-
substrate specificity, overview
-
-
?
additional information
?
-
substrate specificity, overview
-
-
?
additional information
?
-
no activity with citronellal or isopulegol (2-isopropenyl-5-methyl-cyclohexanol)
-
-
?
additional information
?
-
-
product pattern of alternative substrates, overview
-
-
?
additional information
?
-
product pattern of alternative substrates, overview
-
-
?
additional information
?
-
-
mutations lead to altered product pattern
-
-
?
additional information
?
-
-
mutations lead to altered product pattern
-
-
?
additional information
?
-
-
mutations lead to altered product pattern
-
-
?
additional information
?
-
-
mutations lead to altered product pattern
-
-
?
additional information
?
-
-
overview of cyclization products of wild type and mutant enzymes
-
-
?
additional information
?
-
-
overview of cyclization products of wild type and mutant enzymes
-
-
?
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
-
-
?
additional information
?
-
-
enzyme substrate specificity in polycyclization reactions, overview
-
-
?
additional information
?
-
-
no activity with linalool and pseudoionone
-
-
?
additional information
?
-
-
the enzyme also catalyzes 2,3-oxidosqualene cyclization, but no tetrahymanol formation. Substrate specificity, detailed overview
-
-
?
additional information
?
-
the enzyme also catalyzes 2,3-oxidosqualene cyclization, but no tetrahymanol formation. Substrate specificity, detailed overview
-
-
?
additional information
?
-
-
the enzyme shows substrate diversity for polycyclization reactions, since squalene-hopene cyclases specifically address and protonate terminal double bonds of linear terpenoids, molecules with functional groups like carboxylic acids or amides can be used as substrates, overview. It is active with squalene, a C-35 squalene analogue substrate, farnesol, and geranyl geraniol, but not with geraniol, products overview
-
-
?
additional information
?
-
-
no activity with 6-ethylsqualene
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
citronellal
isopulegol
-
-
i.e. 2-isopropenyl-5-methyl-cyclohexanol
-
?
squalene + H2O
hopan-22-ol
-
-
-
-
?
squalene
hop-22(29)-ene
-
-
-
-
?
additional information
?
-
no activity with citronellal or isopulegol (2-isopropenyl-5-methyl-cyclohexanol)
-
-
?
additional information
?
-
-
product pattern of alternative substrates, overview
-
-
?
additional information
?
-
product pattern of alternative substrates, overview
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(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
1-(4-(4-[(4-chloro-phenoxycarbonyl)-methyl-amino]-cyclohexyl)-benzyl)-1-hydroxy-piperidinium
IC50 123 nM
4'-[4-(allyl-methyl-amino)-but-2-enyloxy]-biphenyl-4-yl-(4-bromo-phenyl)-methanone
IC50 29 nM
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-[[3-(4-bromophenyl)-1,2-benzisoxazol-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-amine
-
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
-
allyl-(4-[3-(4-bromo-phenyl)-5-fluoro-1-methyl-1H-indazol-6-yloxy]-but-2-enyl)-methyl-amine
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
methyl-[4-(4-piperidin-1-ylmethyl-phenyl)-cyclohexyl]-carbamic acid 4-chloro-phenyl ester
IC50 406 nM
(18E)-29-methylidenehexanor-2,3-oxidosqualene
-
IC50 0.2 microMol, pH 6.0, 55°C
(1E,3E,7E,11E)-15,16-epoxy-8,12,16-trimethyl-1-methylthio-1,3,7,11-heptadecatetraene
-
IC50 1 microMol, pH 6.0, 55°C
(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, 55°C, 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, 55°C
(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, 55°C, 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, 55°C
(5E,9E)-13,14-epoxy-6,10,14-trimethyl-1-phenylthio-1,5,9-pentadecatriene
-
IC50 7 microMol, pH 6.0, 55°C
(5E,9E,13E)-17,18-epoxy-5,10,14,18-tetramethyl-1-phenylthio-1,5,9,13-nonadecatetraene
-
IC50 3 microMol, pH 6.0, 55°C
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-chlorophenyl methyl(trans-4-[4-[(1-oxidopiperidin-1-yl)methyl]phenyl]cyclohexyl)carbamate
-
-
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-aminium
-
-
6-[[3-(4-bromophenyl)-1-benzofuran-6-yl]oxy]-N-methyl-N-prop-2-en-1-ylhexan-1-aminium
-
-
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'-trimethylethylendiamino)-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-(allylmethylamino)-hexyloxy)chromen-2-one
-
IC50 4-5 microMol
7-(8'-(dimethylamino-N-octyloxy))chromen-2-one
-
IC50 5-7 microMol
dodecyltrimethylammonium bromide
-
competitive inhibition, 50% inhibition at 0.0001 mM
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, 50°C
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, 50°C
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
-
-
allyl-(4-[3-(4-bromo-phenyl)-5-fluoro-1-methyl-1H-indazol-6-yloxy]-but-2-enyl)-methyl-amine
IC50 281 nM
allyl-(4-[3-(4-bromo-phenyl)-5-fluoro-1-methyl-1H-indazol-6-yloxy]-but-2-enyl)-methyl-amine
IC50 332 nM
(5-hydroxycarvacryl)trimethylammonium chloride 1-piperidine carboxylate
-
99% inhibition at 1 mM
(5-hydroxycarvacryl)trimethylammonium chloride 1-piperidine carboxylate
-
i.e. AMO 1618, competitive inhibition
additional information
inhibitors designed as cholesterol-lowering agents, for 11 inhibitors the structures of the enzyme-inhibitor complexes were determined by X-ray crystallography
-
additional information
-
inhibitors designed as cholesterol-lowering agents, for 11 inhibitors the structures of the enzyme-inhibitor complexes were determined by X-ray crystallography
-
additional information
-
vinyl sulfide and ketene dithioacetal derivates of truncated 2,3-ocidosqualene interact with active site of the enzyme
-
additional information
-
effect of thiol-modifying inhibitors on mutant enzymes
-
additional information
-
sulfur-substituted oxidosqualene analogues serve as inhibitors
-
additional information
-
sulfur-containing analogues of 2,3-oxidosqualene inhibit enzyme activity, 50% inhibition at concentrations in the nanomolar range
-
additional information
-
inhibition by n-alkyldimethylammoniumhalides with alkyl chain lengths between 12 and 18 C atoms, inhibition increases with decreasing chain length
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.001
(3S)-2,3-oxidosqualene
-
quintuple mutant, 50°C, pH 6.0
0.0023
(3S)-2,3-oxidosqualene
-
sextuple mutant, 50°C, pH 6.0
0.0279
squalene
-
mutant F605 changed to fluorophenylalanine plus mutation Y606A, pH 6.0, 50°C
0.0324
squalene
-
mutant F605 changed to difluorophenylalanine plus mutation Y606A, pH 6.0, 50°C
0.0352
squalene
-
mutant F365 changed to fluorophenylalanine, pH 6.0, 50°C
0.0416
squalene
-
mutant F365 changed to difluorophenylalanine, pH 6.0, 50°C
0.0479
squalene
-
mutant F6365 changed to trifluorophenylalanine, pH 6.0, 50°C
0.105
squalene
-
mutant F605 changed to O-methyltyrosine, pH 6.0, 40°C
0.152
squalene
-
mutant F605Y changed to O-methyltyrosine, pH 6.0, 50°C
0.185
squalene
-
mutant F365Y changed to O-methyltyrosine, pH 6.0, 50°C
additional information
additional information
-
Km for wild type and mutant enzymes
-
additional information
additional information
-
Km for wild type and mutant enzymes
-
additional information
additional information
-
Km for wild type and mutant enzymes
-
additional information
additional information
-
Km for wild type and mutant enzymes
-
additional information
additional information
-
Km for wild type and mutant enzymes
-
additional information
additional information
-
Km for wild type and mutant enzymes
-
additional information
additional information
-
squalene sextuple mutant: no activity
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.15
squalene
-
mutant F365Y changed to O-methyltyrosine, pH 6.0, 50°C
0.45
squalene
-
mutant F605 changed to O-methyltyrosine, pH 6.0, 40°C
0.54
squalene
-
mutant F605 changed to difluorophenylalanine plus mutation Y606A, pH 6.0, 50°C
0.7
squalene
-
mutant F605Y changed to O-methyltyrosine, pH 6.0, 50°C
0.75
squalene
-
mutant F6365 changed to trifluorophenylalanine, pH 6.0, 50°C
0.82
squalene
-
mutant F605 changed to fluorophenylalanine plus mutation Y606A, pH 6.0, 50°C
0.92
squalene
-
mutant F365 changed to difluorophenylalanine, pH 6.0, 50°C
1.1
squalene
-
mutant F365 changed to fluorophenylalanine, pH 6.0, 50°C
additional information
additional information
-
wild type and mutant enzymes
-
additional information
additional information
-
wild type and mutant enzymes
-
additional information
additional information
-
wild type and mutant enzymes
-
additional information
additional information
-
wild type and mutant enzymes
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00054
(5-hydroxycarvacryl)trimethylammonium chloride 1-piperidine carboxylate
-
-
additional information
additional information
-
Ki for sulfur-substituted oxidosqualene analogues
-
additional information
additional information
-
Ki for sulfur-substituted oxidosqualene analogues
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000059
(4-(2-[(allyl-cyclopropyl-amino)-methyl]-cyclopropylmethoxy)-phenyl)-(4-bromo-phenyl)-methanone
Alicyclobacillus acidocaldarius
IC50 59 nM
0.00005
(4-bromo-phenyl)-(4-(2-[(cyclopropyl-methyl-amino)-methyl]-cyclopropylmethoxy)-2-fluoro-phenyl)-methanone
Alicyclobacillus acidocaldarius
IC50 50 nM
0.000062
(4-bromo-phenyl)-(4-(2-[(cyclopropyl-methyl-amino)-methyl]-cyclopropylmethoxy)-phenyl)-methanone
Alicyclobacillus acidocaldarius
IC50 62 nM
0.000018
(4-bromo-phenyl)-(4-[4-(cyclopropyl-methyl-amino)-but-2-enyloxy]-phenyl)-methanone
Alicyclobacillus acidocaldarius
IC50 18 nM
0.000038
(4-bromo-phenyl)-(4-[6-(cyclopropyl-methyl-amino)-hexyloxy]-2-fluoro-phenyl)-methanone
Alicyclobacillus acidocaldarius
IC50 38 nM
0.0028
(4-chloro-phenyl)-(4-[4-(4,5-dihydro-oxazol-2-yl)-benzylidene]-piperidin-1-yl)-methanone
Alicyclobacillus acidocaldarius
IC50 2800 nM
0.00006
(4-[6-(allyl-methyl-amino)-hexyloxy]-2-fluoro-phenyl)-(4-bromo-phenyl)-methanone
Alicyclobacillus acidocaldarius
IC50 60 nM
0.000096
(4-[6-(allyl-methyl-amino)-hexyloxy]-phenyl)-(4-bromo-phenyl)-methanone
Alicyclobacillus acidocaldarius
IC50 96 nM
0.000123
1-(4-(4-[(4-chloro-phenoxycarbonyl)-methyl-amino]-cyclohexyl)-benzyl)-1-hydroxy-piperidinium
Alicyclobacillus acidocaldarius
IC50 123 nM
0.000029
4'-[4-(allyl-methyl-amino)-but-2-enyloxy]-biphenyl-4-yl-(4-bromo-phenyl)-methanone
Alicyclobacillus acidocaldarius
IC50 29 nM
0.00004
4-[4-(allyl-methyl-amino)-but-2-enyloxy]-phenyl-(4-bromo-phenyl)-methanone
Alicyclobacillus acidocaldarius
IC50 40 nM
0.0012
4-[6-(allyl-methyl-amino)-hexyloxy]-piperidin-1-yl-(4-fluoro-phenyl)-methanone
Alicyclobacillus acidocaldarius
IC50 1200 nM
0.00076
4-[6-(cyclopropyl-methyl-amino)-hexyloxy]-piperidin-1-yl-(4-fluoro-phenyl)-methanone
Alicyclobacillus acidocaldarius
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
Alicyclobacillus acidocaldarius
-
0.000281 - 0.000332
allyl-(4-[3-(4-bromo-phenyl)-5-fluoro-1-methyl-1H-indazol-6-yloxy]-but-2-enyl)-methyl-amine
0.000023
allyl-(4-[3-(4-bromo-phenyl)-benzofuran-6-yloxy]-but-2-enyl)-methyl-amine
Alicyclobacillus acidocaldarius
IC50 23 nM
0.000075
allyl-(4-[3-(4-bromo-phenyl)-benzo[b]thiophen-6-yloxy]-butyl)-methyl-amine
Alicyclobacillus acidocaldarius
IC50 75 nM
0.000049
allyl-(4-[3-(4-bromo-phenyl)-benzo[d]isoxazol-6-yloxy]-but-2-enyl)-amine
Alicyclobacillus acidocaldarius
IC50 49 nM
0.00013
allyl-(4-[4-(6-bromo-benzo[d]isothiazol-3-yl)-phenoxy]-but-2-enyl)-methyl-amine
Alicyclobacillus acidocaldarius
IC50 130 nM
0.000186
allyl-(6-[1-(4-bromo-phenyl)-isoquinolin-6-yloxy]-hexyl)-methyl-amine
Alicyclobacillus acidocaldarius
IC50 186 nM
0.000289
allyl-(6-[3-(4-bromo-phenyl)-1-methyl-1H-indazol-6-yloxy]-hexyl)-methyl-amine
Alicyclobacillus acidocaldarius
IC50 289 nM
0.00018
allyl-(6-[3-(4-bromo-phenyl)-1H-indazol-6-yloxy]-hexyl)-methyl-amine
Alicyclobacillus acidocaldarius
IC50 180 nM
0.00008
allyl-(6-[3-(4-bromo-phenyl)-benzofuran-6-yloxy]-hexyl)-methyl-amine
Alicyclobacillus acidocaldarius
IC50 80 nM
0.000306
allyl-(6-[3-(4-bromo-phenyl)-benzo[d]isothiazol-6-yloxy]-hexyl)-methyl-amine
Alicyclobacillus acidocaldarius
IC50 306 nM
0.000075
allyl-(6-[3-(4-bromo-phenyl)-benzo[d]isoxazol-6-yloxy]-hexyl)-methyl-amine
Alicyclobacillus acidocaldarius
IC50 75 nM
0.000172
allyl-(6-[4-(4-bromo-phenyl)-1H-benzo[d][1,2]oxazin-7-yloxy]-hexyl)-methyl-amine
Alicyclobacillus acidocaldarius
IC50 172 nM
0.000141
allyl-(6-[4-(6-bromo-benzo[d]isothiazol-3-yl)-phenoxy]-hexyl)-methyl-amine
Alicyclobacillus acidocaldarius
IC50 141 nM
0.000406
methyl-[4-(4-piperidin-1-ylmethyl-phenyl)-cyclohexyl]-carbamic acid 4-chloro-phenyl ester
Alicyclobacillus acidocaldarius
IC50 406 nM
0.0002
(18E)-29-methylidenehexanor-2,3-oxidosqualene
Alicyclobacillus acidocaldarius
-
IC50 0.2 microMol, pH 6.0, 55°C
0.001
(1E,3E,7E,11E)-15,16-epoxy-8,12,16-trimethyl-1-methylthio-1,3,7,11-heptadecatetraene
Alicyclobacillus acidocaldarius
-
IC50 1 microMol, pH 6.0, 55°C
0.0014
(1E,3E,7E,11E,15E)-19,20-epoxy-7,12,16,20-tetramethyl-1-methylthio-1,3,7,11,15-heneicosapentaene
Alicyclobacillus acidocaldarius
-
IC50 1.4 microMol, pH 6.0, 55°C, 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
Alicyclobacillus acidocaldarius
-
IC50 4 microMol, pH 6.0, 55°C
0.0018
(1Z,3E,7E,11E,15E)-19,20-epoxy-7,12,16,20-tetramethyl-1-methylthio-1,3,7,11,15-heneicosapentaene
Alicyclobacillus acidocaldarius
-
IC50 1.8 microMol, pH 6.0, 55°C, 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
Alicyclobacillus acidocaldarius
-
IC50 2.2 microMol, pH 6.0, 55°C
0.007
(5E,9E)-13,14-epoxy-6,10,14-trimethyl-1-phenylthio-1,5,9-pentadecatriene
Alicyclobacillus acidocaldarius
-
IC50 7 microMol, pH 6.0, 55°C
0.003
(5E,9E,13E)-17,18-epoxy-5,10,14,18-tetramethyl-1-phenylthio-1,5,9,13-nonadecatetraene
Alicyclobacillus acidocaldarius
-
IC50 3 microMol, pH 6.0, 55°C
0.1
3-(10'-(allylmethylamino)decanoyl)chroman-2,4-dione
Alicyclobacillus acidocaldarius
-
IC50 100 microMol
0.005
7-(10'-(dimethylamino-N-decyloxy))chromen-2-one
Alicyclobacillus acidocaldarius
-
IC50 5 microMol
0.002
7-(10-(allylmethylamino)-decyloxy)chromen-2-one
Alicyclobacillus acidocaldarius
-
IC50 2 microMol
0.005
7-(4'-(N-diethylamino)-but-2-ynyloxy)chromen-2-one
Alicyclobacillus acidocaldarius
-
IC50 5 microMol
0.005
7-(4'-(N-pyrrolidyn)-but-2-ynyloxy)chromen-2-one
Alicyclobacillus acidocaldarius
-
IC50 5 microMol
0.00075
7-(4-allylmethylamino-but-2-ynyloxy)chromen-2-one
Alicyclobacillus acidocaldarius
-
IC50 0.75 microMol
0.008
7-(6'-(benzylamino-hexyloxy))chromen-2-one
Alicyclobacillus acidocaldarius
-
IC50 8 microMol
0.004 - 0.005
7-(6-(allylmethylamino)-hexyloxy)chromen-2-one
Alicyclobacillus acidocaldarius
-
IC50 4-5 microMol
0.005 - 0.007
7-(8'-(dimethylamino-N-octyloxy))chromen-2-one
Alicyclobacillus acidocaldarius
-
IC50 5-7 microMol
0.006
7-(morpholinyl-N-hexyloxy)chromen-2-one
Alicyclobacillus acidocaldarius
-
IC50 6 microMol
0.007
7-(morpholinyl-N-octyloxy)chromen-2-one
Alicyclobacillus acidocaldarius
-
IC50 7 microMol
0.008
7-(piperidinyl-N-hexyloxy)chromen-2-one
Alicyclobacillus acidocaldarius
-
IC50 8 microMol
0.2
N-dodecyliodoacetamide
Alicyclobacillus acidocaldarius
-
IC50 wild-type >200 microMol, quintuple mutant >200 microMol, sextuple mutant >200 microMol, pH 6.0, 50°C
0.000281
allyl-(4-[3-(4-bromo-phenyl)-5-fluoro-1-methyl-1H-indazol-6-yloxy]-but-2-enyl)-methyl-amine
Alicyclobacillus acidocaldarius
IC50 281 nM
0.000332
allyl-(4-[3-(4-bromo-phenyl)-5-fluoro-1-methyl-1H-indazol-6-yloxy]-but-2-enyl)-methyl-amine
Alicyclobacillus acidocaldarius
IC50 332 nM
0.05
N-squalenyliodoacetamide
Alicyclobacillus acidocaldarius
-
IC50 sextuple mutant 50 microMol, pH 6.0, 50°C
0.2
N-squalenyliodoacetamide
Alicyclobacillus acidocaldarius
-
IC50 quintuple mutant >200 microMol
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
specific activities for wild type and mutant enzymes
additional information
-
specific activities for wild type and mutant enzymes
additional information
-
specific activities for wild type and mutant enzymes
additional information
-
specific activities for wild type and mutant enzymes
additional information
-
enzyme activities in mg/ml of product with different substrates and at different enzyme concentrations, overview
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
45
50
50 - 60
55
60
additional information
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
enzyme SHC in vivo is a membrane-associated protein and can be solubilized from cell extracts by nonionic detergents, such as Triton X-100 or octylthioglucopyranoside. The enzyme is attached to the inner side of the cytoplasmic membrane by interactions of hydrophobic residues with the phospholipids. The membrane-binding part of the enzyme is a nonpolar region that is encircled by positive-charged amino acids enforcing the anchoring of the enzyme to the negatively charged surface of the phospholipid membrane
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
enzyme distribution in the different taxa, overview
metabolism
the enzyme converts squalene to hopanol, EC 4.2.1.129, and to hopene, EC 5.4.99.17, but not to tetrahymanol, EC 4.2.1.123, pathway overview
evolution
metabolism
the enzyme is involved in biosynthesis of hopanoids, members of a large group of cyclic triterpenoic compounds that have important functions in many prokaryotic and eukaryotic organisms
physiological function
-
hopene and hopanol are prokaryotic steroid analogues and have important functions as membrane constituents
additional information
evolution
-
squalene hopene cyclases are class II triterpene synthases that use a proton-initiated cationic polycyclization cascade to form carbopolycyclic products. The class II mechanism involves the Broensted acid sequence motif DxDD, catalytic mechanism compared to terpene cyclases, overview
evolution
structure-function relationships of squalene-hopene cyclases, the DXDD motif, which is typical for all squalene-hopene cyclases, overview
additional information
-
structure-function relationships of SHCs, active site structure, overview. A protruding part in the center of the nonpolar region contains a lipophilic channel and directs the substrate to the active-site cavity inside the protein. The channel and cavity are separated by a narrow constriction buildup of four amino acids, D376, F166, C435, and F434, that appear to block access to the active site. Residues C435 and F434 are part of a loop that seems to be flexible enough to permit passage of the substrate and the product
additional information
structure-function relationships of SHCs, active site structure, overview. A protruding part in the center of the nonpolar region contains a lipophilic channel and directs the substrate to the active-site cavity inside the protein. The channel and cavity are separated by a narrow constriction buildup of four amino acids, D376, F166, C435, and F434, that appear to block access to the active site. Residues C435 and F434 are part of a loop that seems to be flexible enough to permit passage of the substrate and the product
additional information
-
structure-function relationships of squalene-hopene cyclases, overview. A large central cavity represents the catalytic site in Alicyclobacillus acidocaldarius enzyme that takes up and orientates the squalene molecule. The channel and active-site cavity inside the protein are separated by a narrow constriction buildup of four amino acids, D376, F166, C435, and F434, that appear to block access to the active site
additional information
structure-function relationships of squalene-hopene cyclases, overview. A large central cavity represents the catalytic site in Alicyclobacillus acidocaldarius enzyme that takes up and orientates the squalene molecule. The channel and active-site cavity inside the protein are separated by a narrow constriction buildup of four amino acids, D376, F166, C435, and F434, that appear to block access to the active site
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
75000
75000
-
2 * 75000, SDS-PAGE, enzyme forms aggregates in absence of detergent
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
-
2 * 75000, SDS-PAGE, enzyme forms aggregates in absence of detergent
additional information
additional information
-
each subunit consists of alpha-helical domains that build up a dumbbell-shaped structure. The first domain consists of a regular (alpha/alpha)6 barrel structure, whereas the second domain shows an alpha-barrel structure in a less periodic manner
additional information
each subunit consists of alpha-helical domains that build up a dumbbell-shaped structure. The first domain consists of a regular (alpha/alpha)6 barrel structure, whereas the second domain shows an alpha-barrel structure in a less periodic manner
additional information
-
dumbbell-shaped structure of chain A with a more structured beta-barrel structure in domain 1, active site structure, structure analysis, overview
additional information
dumbbell-shaped structure of chain A with a more structured beta-barrel structure in domain 1, active site structure, structure analysis, overview
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
complexes with 11 human oxidosqualene cyclase inhibitors produced by cocrystallization, elucidation of the structures by X-ray diffraction analyses
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C435S/D374I/D374V/H451F
site-directed mutagenesis, inactive mutant
D377C/D377N/Y612A
site-directed mutagenesis, the mutant shows an altered product pattern compared to the wild-type enzyme, overview
D377E/D376Q/D376R/D377R/E45K/W406V/W417A/D377C
site-directed mutagenesis, inactive mutant
F365A
F365C
F365G
the mutant shows increased activity with (S)-6,7-epoxygeraniol and no activity with geraniol compared to the wild type enzyme
F601A
F605A
site-directed mutagenesis, the mutant shows an altered product pattern compared to the wild-type enzyme, overview
G600F
the mutant exhibits 68% conversion of geraniol to cyclogeraniol hydrate
I261A
I261W
the mutant shows increased activity with (S)-6,7-epoxygeraniol and no activity with geraniol compared to the wild type enzyme
L36A
the mutant shows increased activity with (S)-6,7-epoxygeraniol compared to the wild type enzyme
Q262G/Q262A/P263G/P263A
site-directed mutagenesis, the mutant shows an altered product pattern compared to the wild-type enzyme, overview
S307A
the mutant shows increased activity with (S)-6,7-epoxygeraniol and no activity with geraniol compared to the wild type enzyme
V381A/D376C
site-directed mutagenesis, inactive mutant
W169F/W169H/W489A/F605K
site-directed mutagenesis, the mutant shows an altered product pattern compared to the wild-type enzyme, overview
Y420A
Y420C
Y420W
the mutant exhibits 54% conversion of (S)-6,7-epoxygeraniol to (1S,3R)-3-(hydroxymethyl)-2,2-dimethyl-4-methylidenecyclohexan-1-ol
Y420W/G600F
the mutant exhibits 78% conversion of (S)-6,7-epoxygeraniol to (1S,3R)-3-(hydroxymethyl)-2,2-dimethyl-4-methylidenecyclohexan-1-ol
Y606A/W23V/W495V/W522V/W533A/W591L/W78S/E35Q/E197Q/D530N/T378A
site-directed mutagenesis, the mutant shows the same product pattern and activity as the wild-type
Y609A/Y612A/L607K
site-directed mutagenesis, the mutant shows an altered product pattern compared to the wild-type enzyme, overview
Y609F
Y612F/D376E/D376G/D377E/D377G/D377Q/E45A/E45D/F365W/T41A/E93A/R127Q/W133A/Y267A/F434A/F437A/W258L/D350N/D421N/D442N/H451R/D447N/D377N/D313N/E535Q/D374E
site-directed mutagenesis, the mutant shows the same product pattern as the wild-type with less enzyme activity
D376E
D376G
-
0.2% activity when enzyme concentration is increased to 100fold
D377C/D377N/Y612A
the mutant shows an altered product pattern compared to the wild-type enzyme, overview
D377E
-
0.2% activity when enzyme concentration is increased to 100fold
D377E/D376Q/D376R/D377R/E45K/W406V/W417A/D377C
inactive mutant
D377G
-
0.2% activity when enzyme concentration is increased to 100fold
D377Q
-
0.2% activity when enzyme concentration is increased to 100fold
E45A
E93A
F365A
the mutant shows an altered product pattern compared to the wild-type enzyme, overview
F365Y
-
and mutant with F365 changed to unnatural amino acid O-methyltyrosine. Both show increased decreased activity at high temperature
F434A
F437A
F601A
the mutant shows an altered product pattern compared to the wild-type enzyme, overview
F605A
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
G262A
-
the mutant produces hopanol as the main product instead of hop-22(29)-ene. The mutant also produces hop-21(22)ene
I261A
P263A
P263G
Q262A
-
mutation located between C29 of the hopanyl cation and the "front water"
Q262G
Q262G/Q262A/P263G/P263A
the mutant shows an altered product pattern compared to the wild-type enzyme, overview
R127Q
T41A
W133A
W169A
-
the mutant has higher activity with (S)-citronellal compared to the wild type enzyme
W169F/W169H/W489A/F605K
the mutant shows an altered product pattern compared to the wild-type enzyme, overview
W23V
-
same activity and optimal temperature as wild type enzyme
W312G
-
the mutant produces (-)-neo-isopulegol from (S)-citronellal
W485V
-
same activity and optimal temperature as wild type enzyme
W522V
-
same activity and optimal temperature as wild type enzyme
W533A
-
same activity and optimal temperature as wild type enzyme
W591L
-
same activity and optimal temperature as wild type enzyme
W78S
-
same activity and optimal temperature as wild type enzyme
Y267A
Y420A
the mutant shows an altered product pattern compared to the wild-type enzyme, overview
Y606A/W23V/W495V/W522V/W533A/W591L/W78S/E35Q/E197Q/D530N/T378A
the mutant shows the same product pattern and activity as the wild-type
Y609A
-
the mutant produces (+)-isopulegol from (S)-citronellal
Y609A/Y612A/L607K
the mutant shows an altered product pattern compared to the wild-type enzyme, overview
Y609F
Y612F/D376E/D376G/D377E/D377G/D377Q/E45A/E45D/F365W/T41A/E93A/R127Q/W133A/Y267A/F434A/F437A/W258L/D350N/D421N/D442N/H451R/D447N/D377N/D313N/E535Q/D374E
the mutant shows the same product pattern as the wild-type with less enzyme activity
additional information
F365A
site-directed mutagenesis, the mutant shows an altered product pattern compared to the wild-type enzyme, overview
F365A
the mutant shows increased activity with geraniol and (S)-6,7-epoxygeraniol compared to the wild type enzyme
F365C
the mutant exhibits 15% conversion of geraniol to gamma-cyclogeraniol
F365C
the mutant shows increased activity with geraniol compared to the wild type enzyme
F601A
site-directed mutagenesis, the mutant shows an altered product pattern compared to the wild-type enzyme, overview
I261A
site-directed mutagenesis, the mutant shows an altered product pattern compared to the wild-type enzyme, overview
I261A
the mutant exhibits 11% conversion of citronellal to (-)-iso-isopulegol. The mutant shows increased activity with geraniol and (S)-6,7-epoxygeraniol compared to the wild type enzyme
Y420A
site-directed mutagenesis, the mutant shows an altered product pattern compared to the wild-type enzyme, overview
Y420C
site-directed mutagenesis, the mutant performs interconversion of citronellal and isopulegol
Y609F
site-directed mutagenesis, the mutant shows an altered product pattern compared to the wild-type enzyme, overview
Y609F
site-directed mutagenesis, the mutant shows an altered product pattern compared to the wild-type enzyme, overview. The phenotype of Y609F mutein is contrarily described in two publications
E45A
-
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
E93A
-
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
F434A
-
production of hop-22(29)-ene is decreased, production of hopanol is markedly increased at lower temperatures
F437A
-
production of hop-22(29)-ene is decreased, production of hopanol is markedly increased at lower temperatures
F605A
the mutant shows an altered product pattern compared to the wild-type enzyme, overview
I261A
the mutant shows an altered product pattern compared to the wild-type enzyme, overview
I261A
-
the mutant has higher activity with (S)-citronellal compared to the wild type enzyme
P263A
-
mutation located between C29 of the hopanyl cation and the "front water"
P263A
-
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"
P263G
-
the mutant produces hopanol as the main product instead of hop-22(29)-ene. The mutant also produces hop-21(22)ene
Q262G
-
mutation located between C29 of the hopanyl cation and the "front water"
Q262G
-
the mutant produces hopanol as the main product instead of hop-22(29)-ene. The mutant also produces hop-21(22)ene
R127Q
-
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
-
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
-
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
Y267A
-
production of hop-22(29)-ene is decreased, production of hopanol is markedly increased at lower temperatures
Y609F
the mutant shows an altered product pattern compared to the wild-type enzyme, overview
additional information
-
modification of critically located Cys residues
additional information
-
various mutations of conserved amino acid residues
additional information
-
mutations of Y609, Y495, Y612 and Y420 lead to an altered product pattern, compared to wild-type enzyme
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
additional information
-
product patterns of mutant enzymes, detailed overview
additional information
product patterns of mutant enzymes, detailed overview
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
60
-
wild type enzyme: 50% loss of activity after 120 min, D376E mutant: 50% loss of activity after 100 min
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
bicontinuous microemulsions can be used as reaction media for enzyme-catalysed reactions
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
native and/or recombinant enzyme, the enzyme in vivo is a membrane-associated protein and can be solubilized from cell extracts by nonionic detergents, such as Triton X-100 or octylthioglucopyranoside
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene shc, DNA and amino acid sequence determination, expression in Escherichia coli
-
-
DNA and amino acid sequence determination and analysis, sequence comparison, expression in Escherichia coli strain DH5alpha
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
synthesis
-
production of unnatural polyprenoids and supranatural steroids by manipulation of the enzyme reaction by combination of substrate analogues
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Ceruti, M.; Balliano, G.; Rocco, F.; Milla, P.; Arpicco, S.; Cattel, L.; Viola, F.
Vinyl sulfide derivatives of truncated oxidosqualene as selective inhibitors of oxidosqualene and squalene-hopene cyclases
Lipids
36
629-636
2001
Alicyclobacillus acidocaldarius
Dang, T.; Prestwich, G.D.
Site-directed mutagenesis of squalene-hopene cyclase: altered substrate specificity and product distribution
Chem. Biol.
7
643-649
2000
Alicyclobacillus acidocaldarius
Feil, C.; Suessmuth, R.; Jung, G.; Poralla, K.
Site-directed mutagenesis of putative active-site residues in squalene-hopene cyclase
Eur. J. Biochem.
242
51-55
1996
Alicyclobacillus acidocaldarius
Full, C.
Bicyclic triterpenes as new main products of squalene-hopene cyclase by mutation at conserved tyrosine residues
FEBS Lett.
509
361-364
2001
Alicyclobacillus acidocaldarius
Full, C.; Poralla, K.
Conserved Tyr residues determine functions of Alicyclobacillus acidocaldarius squalene-hopene cyclase
FEMS Microbiol. Lett.
183
221-224
2000
Alicyclobacillus acidocaldarius
Hoshino, T.; Kouda, M.; Abe, T.; Sato, T.
Functional analysis of Phe605, a conserved aromatic amino acid in squalene-hopene cyclases
Chem. Commun. (Camb.)
2000
1485-1486
2000
Alicyclobacillus acidocaldarius
-
Hoshino, T.; Sato, T.
Squalene-hopene cyclase: catalytic mechanism and substrate recognition
Chem. Commun. (Camb.)
2000
291-301
2002
Alicyclobacillus acidocaldarius
-
Milla, P.; Lenhart, A.; Grosa, G.; Viola, F.; Weihofen, W.A.; Schulz, G.E.; Balliano, G.
Thiol-modifying inhibitors for understanding squalene cyclase function
Eur. J. Biochem.
269
2108-2116
2002
Alicyclobacillus acidocaldarius
Ochs, D.; Tappe, C.H.; Gaertner, P.; Kellner, R.; Poralla, K.
Properties of purified squalene-hopene cyclase from Bacillus acidocaldarius
Eur. J. Biochem.
194
75-80
1990
Alicyclobacillus acidocaldarius
Sato, T.; Hoshino, T.
Functional analysis of the DXDDTA motif in squalene-hopene cyclase by site-directed mutagenesis experiments: initiation site of the polycyclization reaction and stabilization site of the carbocation intermediate of the initially cyclized A-ring
Biosci. Biotechnol. Biochem.
63
2189-2198
1999
Alicyclobacillus acidocaldarius
Sato, T.; Hoshino, T.
Kinetic studies on the function of all the conserved tryptophans involved inside and outside the QW motifs of squalene-hopene cyclase: stabilizing effect of the protein structure against thermal denaturation
Biosci. Biotechnol. Biochem.
63
1171-1180
1999
Alicyclobacillus acidocaldarius
Sato, T.; Sasahara, S.; Yamakami, T.; Hoshino, T.
Functional analyses of Tyr420 and Leu607 of Alicyclobacillus acidocaldarius squalene-hopene cyclase. Neoachillapentaene, a novel triterpene with the 1,5,6-trimethylcyclohexene moiety produced through folding of the constrained boat structure
Biosci. Biotechnol. Biochem.
66
1660-1670
2002
Alicyclobacillus acidocaldarius
Seckler, B.; Poralla, K.
Characterization and partial purification of squalene-hopene cyclase from Bacillus acidocaldarius
Biochim. Biophys. Acta
881
356-363
1986
Alicyclobacillus acidocaldarius, Alicyclobacillus acidocaldarius 104-IA
-
Wendt, K.U.; Lenhart, A.; Schulz, G.E.
The structure of the membrane protein squalene-hopene cyclase at 2.0.ANG. resolution
J. Mol. Biol.
286
175-187
1999
Alicyclobacillus acidocaldarius (P33247), Alicyclobacillus acidocaldarius
Zheng, Y.F.; Abe, I.; Prestwich, G.D.
Inhibition kinetics and affinity labeling of bacterial squalene:hopene cyclase by thia-substituted analogs of 2,3-oxidosqualene
Biochemistry
37
5981-5987
1998
Alicyclobacillus acidocaldarius
Sato, T.; Kouda, M.; Hoshino, T.
Site-directed mutagenesis experiments on the putative deprotonation site of squalene-hopene cyclase from Alicyclobacillus acidocaldarius
Biosci. Biotechnol. Biochem.
68
728-738
2004
Alicyclobacillus acidocaldarius
Reinert, D.J.; Balliano, G.; Schulz, G.E.
Conversion of squalene to the pentacarbocyclic hopene
Chem. Biol.
11
121-126
2004
Alicyclobacillus acidocaldarius
Cravotto, G.; Balliano, G.; Tagliapietra, S.; Palmisano, G.; Penoni, A.
Umbelliferone aminoalkyl derivatives, a new class of squalene-hopene cyclase inhibitors
Eur. J. Med. Chem.
39
917-924
2004
Alicyclobacillus acidocaldarius
Lenhart, A.; Reinert, D.J.; Aebi, J.D.; Dehmlow, H.; Morand, O.H.; Schulz, G.E.
Binding structures and potencies of oxidosqualene cyclase inhibitors with the homologous squalene-hopene cyclase
J. Med. Chem.
46
2083-2092
2003
Alicyclobacillus acidocaldarius (P33247), Alicyclobacillus acidocaldarius
Rocco, F.; Bosso, S.O.; Viola, F.; Milla, P.; Roma, G.; Grossi, G.; Ceruti, M.
Conjugated methyl sulfide and phenyl sulfide derivatives of oxidosqualene as inhibitors of oxidosqualene and squalene-hopene cyclases
Lipids
38
201-207
2003
Alicyclobacillus acidocaldarius
Ceruti, M.; Balliano, G.; Rocco, F.; Lenhart, A.; Schulz, G.E.; Castelli, F.; Milla, P.
Synthesis and biological activity of new iodoacetamide derivatives on mutants of squalene-hopene cyclase
Lipids
40
729-735
2005
Alicyclobacillus acidocaldarius
Nakano, S.; Ohashi, S.; Hoshino, T.
Squalene-hopene cyclase: insight into the role of the methyl group on the squalene backbone upon the polycyclization cascade. Enzymatic cyclization products of squalene analogs lacking a 26-methyl group and possessing a methyl group at C7 or C11
Org. Biomol. Chem.
2
2012-2022
2004
Alicyclobacillus acidocaldarius
Tanaka, H.; Noguchi, H.; Abe, I.
Enzymatic formation of indole-containing unnatural cyclic polyprenoids by bacterial squalene:hopene cyclase
Org. Lett.
7
5873-5876
2005
Alicyclobacillus acidocaldarius
Morikubo, N.; Fukuda, Y.; Ohtake, K.; Shinya, N.; Kiga, D.; Sakamoto, K.; Asanuma, M.; Hirota, H.; Yokoyama, S.; Hoshino, T.
Cation-pi interaction in the polyolefin cyclization cascade uncovered by incorporating unnatural amino acids into the catalytic sites of squalene cyclase
J. Am. Chem. Soc.
128
13184-13194
2006
Alicyclobacillus acidocaldarius
Tanaka, H.; Noma, H.; Noguchi, H.; Abe, I.
Enzymatic formation of pyrrole-containing novel cyclic polyprenoids by bacterial squalene:hopene cyclase
Tetrahedron Lett.
47
3085-3089
2006
Alicyclobacillus acidocaldarius
-
Schwab, F.; van Gunsteren, W.F.; Zagrovic, B.
Computational study of the mechanism and the relative free energies of binding of anticholesteremic inhibitors to squalene-hopene cyclase
Biochemistry
47
2945-2951
2008
Alicyclobacillus acidocaldarius (P33247)
Hoshino, T.; Kumai, Y.; Sato, T.
Reviewing the polyolefin cyclization reaction of the C(35) polyprene catalyzed by squalene-hopene cyclase
Chemistry
15
2091-2100
2009
Alicyclobacillus acidocaldarius
Ermondi, G.; Caron, G.
GRIND-based 3D-QSAR to predict inhibitory activity for similar enzymes, OSC and SHC
Eur. J. Med. Chem.
43
1462-1468
2008
Alicyclobacillus acidocaldarius
Cheng, J.; Hoshino, T.
Cyclization cascade of the C33-bisnorheptaprenoid catalyzed by recombinant squalene cyclase
Org. Biomol. Chem.
7
1689-1699
2009
Alicyclobacillus acidocaldarius
Siedenburg, G.; Jendrossek, D.
Squalene-hopene cyclases
Appl. Environ. Microbiol.
77
3905-3915
2011
Alicyclobacillus acidocaldarius, Alicyclobacillus acidocaldarius (P33247), Bradyrhizobium japonicum, Methylococcus capsulatus, Rhodopseudomonas palustris, Streptomyces peucetius, Tetrahymena thermophila, Zymomonas mobilis, no activity in Methylococcus capsulatus
Siedenburg, G.; Breuer, M.; Jendrossek, D.
Prokaryotic squalene-hopene cyclases can be converted to citronellal cyclases by single amino acid exchange
Appl. Microbiol. Biotechnol.
97
1571-1580
2013
Bradyrhizobium japonicum, Rhodopseudomonas palustris, Teredinibacter turnerae, Syntrophobacter fumaroxidans (A0LJS0), Alicyclobacillus acidocaldarius (P33247), Zymomonas mobilis (P33990), Zymomonas mobilis (Q5NM88), Burkholderia ambifaria (Q0B2H5), Burkholderia ambifaria (Q0B5S3), Bacillus anthracis (Q81YD8), Streptomyces coelicolor (Q9X7V9), Acetobacter pasteurianus (YP3187836), Burkholderia ambifaria ATCC BAA-244 / AMMD (Q0B2H5), Burkholderia ambifaria ATCC BAA-244 / AMMD (Q0B5S3), Zymomonas mobilis ATCC 31821 (P33990), Zymomonas mobilis CP4 (Q5NM88), Alicyclobacillus acidocaldarius DSM 446 (P33247)
Seitz, M.; Syren, P.; Steiner, L.; Klebensberger, J.; Nestl, B.; Hauer, B.
Synthesis of heterocyclic terpenoids by promiscuous squalene-hopene cyclases
ChemBioChem
14
436-439
2013
Alicyclobacillus acidocaldarius, Zymomonas mobilis
Hammer, S.C.; Syren, P.O.; Seitz, M.; Nestl, B.M.; Hauer, B.
Squalene hopene cyclases: highly promiscuous and evolvable catalysts for stereoselective CC and CX bond formation
Curr. Opin. Chem. Biol.
17
293-300
2013
Alicyclobacillus acidocaldarius
Yonemura, Y.; Ohyama, T.; Hoshino, T.
Chemo-enzymatic syntheses of drimane-type sesquiterpenes and the fundamental core of hongoquercin meroterpenoid by recombinant squalene-hopene cyclase
Org. Biomol. Chem.
10
440-446
2012
Alicyclobacillus acidocaldarius
Bastian, S.; Hammer, S.; Kre, N.; Nestl, B.; Hauer, B.
Selectivity in the cyclization of citronellal introduced by squalene hopene cyclase variants
ChemCatChem
9
4364-4368
2017
Alicyclobacillus acidocaldarius
-
Kaneko, I.; Terasawa, Y.; Hoshino, T.
Squalene-hopene cyclase mechanistic insights into the polycyclization cascades of squalene analogs bearing ethyl and hydroxymethyl groups at the C-2 and C-23 positions
Chemistry
24
11139-11157
2018
Alicyclobacillus acidocaldarius
Steudle, A.K.; Nestl, B.M.; Hauer, B.; Stubenrauch, C.
Activity of squalene-hopene cyclases in bicontinuous microemulsions
Colloids Surf. B Biointerfaces
135
735-741
2015
Alicyclobacillus acidocaldarius
Takahashi, K.; Sasaki, Y.; Hoshino, T.
Squalene-hopene cyclase on the polycyclization reactions of squalene analogues bearing ethyl groups at positions C-6, C-10, C-15, and C-19
Eur. J. Org. Chem.
2018
1477-1490
2018
Alicyclobacillus acidocaldarius
-
Hammer, S.C.; Marjanovic, A.; Dominicus, J.M.; Nestl, B.M.; Hauer, B.
Squalene hopene cyclases are protonases for stereoselective Bronsted acid catalysis
Nat. Chem. Biol.
11
121-126
2015
Alicyclobacillus acidocaldarius (P33247)
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