Information on EC 5.4.99.17 - squalene-hopene cyclase

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

SplaateEC_Number,Commentary
EC NUMBER
COMMENTARY
5.4.99.17
-
SplaateRecommended_Name,GO_Number
RECOMMENDED NAME
GeneOntology No.
squalene-hopene cyclase
-
SplaateReaction,Reaction_id,Commentary,IF(Commentary != '',Organism,'') ,IF(Commentary != '',Literature,'')
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
squalene + H2O = hopan-22-ol
show the reaction diagram
-
-
-
-
squalene = hop-22(29)-ene
show the reaction diagram
-
-
-
-
squalene = hop-22(29)-ene
show the reaction diagram
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; overall mechanism of the polycyclization reaction of SHCs and structures of squalene cyclization products, overview
squalene = hop-22(29)-ene
show the reaction diagram
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, overview; overall mechanism of the polycyclization reaction of SHCs and structures of squalene cyclization products, overview
-
squalene = hop-22(29)-ene
show the reaction diagram
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, overview
-
squalene = hop-22(29)-ene
show the reaction diagram
catalytic mechanism, overview
-
squalene = hop-22(29)-ene
show the reaction diagram
catalytic mechanism via Friedel-Crafts alkylation and substrate specificity, overview
-
SplaateReaction_Type,Organism,Commentary,Literature
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
cyclization
-
-
-
-
SplaatePathway,BRENDA_Link,KEGG_Link,MetaCyc_Link,Source_Database
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
diploterol and cycloartenol biosynthesis
-
-
hopanoid biosynthesis (bacteria)
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Sesquiterpenoid and triterpenoid biosynthesis
-
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SplaateSystematic_Name,Commentary_IUBMB
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.
SplaateSynonyms,Organism,Commentary,Literature
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
cyclase, squalene-hopanoid
-
-
-
-
SHC
-
-
-
-
SHC
Alicyclobacillus acidocaldarius DSM 446
-
-
SHC
Burkholderia ambifaria ATCC BAA-244/AMMD
-
-
SHC
Zymomonas mobilis ZMO-0872
-
-
SHC
Zymomonas mobilis ZMO-1548
-
-
SHC1
Burkholderia ambifaria ATCC BAA-244/AMMD
-
-
SHC2
Burkholderia ambifaria ATCC BAA-244/AMMD
-
-
squalene hopene cyclase
-
-
squalene hopene cyclase
-
squalene hopene cyclase
-
squalene-hopene cyclase
-
-
squalene-hopene cyclase
-
squalene-hopene cyclase
-
-
SplaateCAS_Registry_Number,Commentary
CAS REGISTRY NUMBER
COMMENTARY
76600-69-6
-
SplaateOrganism, Commentary,Literature, Sequence_Code,Sequence_db,Textmining
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
YP3187836
GenBank
Manually annotated by BRENDA team
formerly Bacillus acidocaldarius
-
-
Manually annotated by BRENDA team
formerly Bacillus acidocaldarius, gene shc
Uniprot
Manually annotated by BRENDA team
Alicyclobacillus acidocaldarius 104-IA
strain 104-IA
-
-
Manually annotated by BRENDA team
Alicyclobacillus acidocaldarius DSM 446
-
Uniprot
Manually annotated by BRENDA team
Burkholderia ambifaria ATCC BAA-244/AMMD
-
UniProt
Manually annotated by BRENDA team
Methylococcus capsulatus Bath
strain Bath
-
-
Manually annotated by BRENDA team
no activity in Methylococcus capsulatus
-
-
-
Manually annotated by BRENDA team
gene slr2089
UniProt
Manually annotated by BRENDA team
gene ZMO1548
-
-
Manually annotated by BRENDA team
gene ZMO1548
UniProt
Manually annotated by BRENDA team
Zymomonas mobilis ZMO-0872
-
UniProt
Manually annotated by BRENDA team
Zymomonas mobilis ZMO-1548
-
UniProt
Manually annotated by BRENDA team
SplaateGeneral_Information, Organism, Commentary, Literature
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
enzyme distribution in the different taxa, overview; structure-function relationships of squalene-hopene cyclases, the DXDD motif, which is typical for all squalene-hopene cyclases, overview
evolution
-
enzyme distribution in the different taxa, overview; structure-function relationships of squalene-hopene cyclases, the DXDD motif, which is typical for all squalene-hopene cyclases, overview
evolution
-
structure-function relationships of squalene-hopene cyclases, the DXDD motif, which is typical for all squalene-hopene cyclases, overview
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
malfunction
inactivation of slr2089 leads to accumulation of squalene to a level over 70times higher than in wild-type cells, but no significant growth deficiency in the DELTAshc strain occur compared to the wild-type Synechocystis even at high light conditions
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; 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
metabolism
-
the enzyme converts squalene to tetrahymanol, EC 4.2.1.123, to hopene, EC 5.4.99.17, and to hopanol, EC 4.2.1.129, pathway overview; 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
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
metabolism
-
the nezym eis involved in biosynthesis of hopanoids, members of a large group of cyclic triterpenoic compounds that have important functions in many prokaryotic and eukaryotic organisms
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
metabolism
the enzyme converts squalene into hopene, the substrate for forming hopanoids
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; 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 SHCs, active site structure, overview; structure-function relationships of squalene-hopene cyclases, overview
additional information
-
structure-function relationships of squalene-hopene cyclases, overview
additional information
-
the enzyme catalyzes the cyclization of triterpenoids via cationic intermediates in one of the most complex reactions known in biochemistry
SplaateSubstrates,Products,id,Organism_Substrates,Commentary_Substrates, Literature_Substrates, Commentary_Products, Literature_Products,Reversibility
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(3S)-2,3-oxidosqualene
lanosterol
show the reaction diagram
-
-
-
?
(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
show the reaction diagram
-
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
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-((2E,6E)-3,7,11-trimethyldodeca-2,6,10-trienyl)phenol
(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 + (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-yl acetate
show the reaction diagram
-
-
-
?
2-((2E,6E)-9-(3,3-dimethyloxiran-2-yl)-3,7-dimethylnona-2,6-diethyl)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
show the reaction diagram
-
-
-
?
2-(farnesyldimethylallyl)pyrrole
?
show the reaction diagram
-
-
product is a 10:1 mixture of a tricyclic and a bicyclic unnatural polyprenoid
-
?
3,7,11-trimethyldodeca-1,6,10-trien-3-ol
(-)-caparrapioxide + (-)-8-epi-caparrapioxide
show the reaction diagram
-
-
-
-
3-(farnesyldimethylallyl)indole
?
show the reaction diagram
-
-
conversion into a 2:1 mixture of a tetracyclic and a pentacyclic product
-
?
C33 polyprene
?
show the reaction diagram
-
the enzymatic products consist of mono-, bi-, tri-, tetra- and pentacyclic skeletons, however, hexacyclic products are not generated
-
-
?
citronellal
isopulegol
show the reaction diagram
-
-
i.e. 2-isopropenyl-5-methyl-cyclohexanol
?
citronellal
isopulegol
show the reaction diagram
-
i.e. 2-isopropenyl-5-methyl-cyclohexanol
?
citronellal
isopulegol
show the reaction diagram
-
i.e. 2-isopropenyl-5-methyl-cyclohexanol
?
citronellal
isopulegol
show the reaction diagram
-
-
i.e. 2-isopropenyl-5-methyl-cyclohexanol
?
citronellal
isopulegol
show the reaction diagram
activity of mutant F438C, not of the wild-type enzyme
i.e. 2-isopropenyl-5-methyl-cyclohexanol
?
citronellal
isopulegol
show the reaction diagram
-
activity of mutant F447C, not of the wild-type enzyme
i.e. 2-isopropenyl-5-methyl-cyclohexanol
?
citronellal
isopulegol
show the reaction diagram
activity of mutant F449C, not of the wild-type enzyme
i.e. 2-isopropenyl-5-methyl-cyclohexanol
?
citronellal
isopulegol
show the reaction diagram
YP3187836
activity of mutant F481C, not of the wild-type enzyme
i.e. 2-isopropenyl-5-methyl-cyclohexanol
?
citronellal
isopulegol
show the reaction diagram
-
activity of mutant Y420C, not of the wild-type enzyme
i.e. 2-isopropenyl-5-methyl-cyclohexanol
?
citronellal
isopulegol
show the reaction diagram
wild-type enzyme, and increased activity in mutant F486C
i.e. 2-isopropenyl-5-methyl-cyclohexanol
?
citronellal
isopulegol
show the reaction diagram
Alicyclobacillus acidocaldarius DSM 446
activity of mutant Y420C, not of the wild-type enzyme
i.e. 2-isopropenyl-5-methyl-cyclohexanol
?
citronellal
isopulegol
show the reaction diagram
Zymomonas mobilis ZMO-0872
activity of mutant F438C, not of the wild-type enzyme
i.e. 2-isopropenyl-5-methyl-cyclohexanol
?
citronellal
isopulegol
show the reaction diagram
Zymomonas mobilis ZMO-1548
wild-type enzyme, and increased activity in mutant F486C
i.e. 2-isopropenyl-5-methyl-cyclohexanol
?
compound 5
(-)-caparrapioxide + (-)-8-epi-caparrapioxide
show the reaction diagram
-
-
-
?
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
show the reaction diagram
-
-
drimane-type sequiterpenes
?
farnesyl phenyl ether
(4aS,5S,8aS)-1,1,4a,6-tetramethyl-5-(phenoxymethyl)-1,2,3,4,4a,5,8,8a-octahydronaphthalene + (4aS,4bR,10bR,12aS)-1,1,4a,10b-tetramethyl-2,3,4,4a,4b,5,10b,11,12,12a-decahydro-1H-naphtho[1,2-c]chromene
show the reaction diagram
-
-
-
?
farnesylacetone
sclareoloxide
show the reaction diagram
-
-
-
?
geranyl phenyl ether
(6aS,10aS)-7,7,10a-trimethyl-6a,7,8,9,10,10a-hexahydro-6H-benzo[c]chromene
show the reaction diagram
-
-
-
?
geranylacetone
(8aS)-2,5,5,8a-tetramethyl-4a,5,6,7,8,8a-hexahydro-4H-chromene
show the reaction diagram
-
-
-
?
geranylgeranyl phenyl ether
(14b)-8,13-dimethyl-14-(phenoxymethyl)podocarp-12-ene + (14b)-8-methyl-13-methylidene-14-(phenoxymethyl)podocarpane
show the reaction diagram
-
-
-
?
homofarnesoic acid
sclareolide
show the reaction diagram
-
-
-
?
homofarnesol
ambroxan
show the reaction diagram
-
-
?
homofarnesol
ambroxan
show the reaction diagram
-
-
-
?
hongoquercin A
?
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
-
-
-
?
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
-
-
-
?
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
YP3187836
-
-
?
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
-
-
hopanol is also formed
?
squalene
hop-22(29)-ene
show the reaction diagram
-
-
the enzyme from Alicyclobacillus acidocaldarius yields pentacyclic hopene and hopanol (diplopterol) via a hopanyl cation from squalene
?
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
Burkholderia ambifaria ATCC BAA-244/AMMD
-
-
?
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
hop-22(29)-ene
show the reaction diagram
Alicyclobacillus acidocaldarius DSM 446
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
Zymomonas mobilis ZMO-0872
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
Zymomonas mobilis ZMO-1548
-
-
?
squalene
hop-22(29)-ene + hopanol
show the reaction diagram
-
-
?
squalene
hop-22(29)-ene + hopanol
show the reaction diagram
-
-
-
?
squalene
hop-22(29)-ene + hopanol
show the reaction diagram
-
the enzyme catalyzes cyclization of the linear triterpenoid squalene to hopene and hopanol by the class II mechanism
-
?
hongoquercin B
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
substrate specificity, overview
-
-
-
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
-
-
-
additional information
?
-
-
no activity with citronellal or isopulegol (2-isopropenyl-5-methyl-cyclohexanol)
-
-
-
additional information
?
-
no activity with citronellal or isopulegol (2-isopropenyl-5-methyl-cyclohexanol)
-
-
-
additional information
?
-
YP3187836
no activity with citronellal or isopulegol (2-isopropenyl-5-methyl-cyclohexanol)
-
-
-
additional information
?
-
no activity with citronellal or isopulegol (2-isopropenyl-5-methyl-cyclohexanol)
-
-
-
additional information
?
-
-
no activity with citronellal or isopulegol (2-isopropenyl-5-methyl-cyclohexanol)
-
-
-
additional information
?
-
no activity with citronellal or isopulegol (2-isopropenyl-5-methyl-cyclohexanol)
-
-
-
additional information
?
-
no activity with citronellal or isopulegol (2-isopropenyl-5-methyl-cyclohexanol)
-
-
-
additional information
?
-
no activity with citronellal or isopulegol (2-isopropenyl-5-methyl-cyclohexanol)
-
-
-
additional information
?
-
-
enzyme substrate specificity in polycyclization reactions, overview
-
-
-
additional information
?
-
-
no activity with linalool and pseudoionone
-
-
-
additional information
?
-
-
substrate specificity, detailed overview
-
-
-
additional information
?
-
-
substrate specificity, overview. No activity with prenyl phenyl ether
-
-
-
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 also catalyzes 2,3-oxidosqualene cyclization, substrate specificity, detailed overview
-
-
-
additional information
?
-
-
the enzyme does not catalyze 2,3-oxidosqualene cyclization nor tetrahymanol formation. Substrate specificity, detailed overview
-
-
-
additional information
?
-
-
the enzyme does not catalyze 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
?
-
ZmoSHC1 shows cyclization of the non-natural substrates homofarnesol (C16) and citronellal (C10) in addition to hopene formation from squalene, substrate specificity, overview. ZmoSHC1 exhibits a shift of activity towards substrates of shorter chain lengths, displaying over 50fold higher conversion of homofarnesol and more than 2fold higher conversion of citronellal in comparison to squalene conversion
-
-
-
additional information
?
-
product pattern of alternative substrates, overview
-
-
-
additional information
?
-
Burkholderia ambifaria ATCC BAA-244/AMMD
no activity with citronellal or isopulegol (2-isopropenyl-5-methyl-cyclohexanol)
-
-
-
additional information
?
-
Alicyclobacillus acidocaldarius DSM 446
no activity with citronellal or isopulegol (2-isopropenyl-5-methyl-cyclohexanol)
-
-
-
additional information
?
-
Zymomonas mobilis ZMO-0872
no activity with citronellal or isopulegol (2-isopropenyl-5-methyl-cyclohexanol)
-
-
-
SplaateNatural_Substrates,Natural_Products,id,Organism_Substrates,Commentary_Substrates,Literature_Substrates,Commentary_Products,Literature_Products,Reversibility
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
citronellal
isopulegol
show the reaction diagram
-
-
i.e. 2-isopropenyl-5-methyl-cyclohexanol
?
citronellal
isopulegol
show the reaction diagram
P33990, Q5NM88
-
i.e. 2-isopropenyl-5-methyl-cyclohexanol
?
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
P33247
-
-
?
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
P33990, Q5NM88
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
YP3187836
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
A0LJS0
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
Q81YD8
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
Q9X7V9
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
Q0B2H5, Q0B5S3
-
-
?
squalene
hop-22(29)-ene + hopanol
show the reaction diagram
Q5NM88
-
-
?
squalene
hop-22(29)-ene + hopanol
show the reaction diagram
-
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
Burkholderia ambifaria ATCC BAA-244/AMMD
Q0B2H5, Q0B5S3
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
Alicyclobacillus acidocaldarius DSM 446
P33247
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
Zymomonas mobilis ZMO-0872
P33990
-
-
?
squalene
hop-22(29)-ene
show the reaction diagram
Zymomonas mobilis ZMO-1548
Q5NM88
-
-
?
citronellal
isopulegol
show the reaction diagram
Zymomonas mobilis ZMO-1548
Q5NM88
-
i.e. 2-isopropenyl-5-methyl-cyclohexanol
?
additional information
?
-
-
no activity with citronellal or isopulegol (2-isopropenyl-5-methyl-cyclohexanol)
-
-
-
additional information
?
-
P33990, Q5NM88
no activity with citronellal or isopulegol (2-isopropenyl-5-methyl-cyclohexanol)
-
-
-
additional information
?
-
YP3187836
no activity with citronellal or isopulegol (2-isopropenyl-5-methyl-cyclohexanol)
-
-
-
additional information
?
-
A0LJS0
no activity with citronellal or isopulegol (2-isopropenyl-5-methyl-cyclohexanol)
-
-
-
additional information
?
-
-
no activity with citronellal or isopulegol (2-isopropenyl-5-methyl-cyclohexanol)
-
-
-
additional information
?
-
Q81YD8
no activity with citronellal or isopulegol (2-isopropenyl-5-methyl-cyclohexanol)
-
-
-
additional information
?
-
Q9X7V9
no activity with citronellal or isopulegol (2-isopropenyl-5-methyl-cyclohexanol)
-
-
-
additional information
?
-
Q0B2H5, Q0B5S3
no activity with citronellal or isopulegol (2-isopropenyl-5-methyl-cyclohexanol)
-
-
-
additional information
?
-
P33247
product pattern of alternative substrates, overview
-
-
-
additional information
?
-
Burkholderia ambifaria ATCC BAA-244/AMMD
Q0B2H5, Q0B5S3
no activity with citronellal or isopulegol (2-isopropenyl-5-methyl-cyclohexanol)
-
-
-
additional information
?
-
Alicyclobacillus acidocaldarius DSM 446
P33247
no activity with citronellal or isopulegol (2-isopropenyl-5-methyl-cyclohexanol)
-
-
-
additional information
?
-
Zymomonas mobilis ZMO-0872
P33990
no activity with citronellal or isopulegol (2-isopropenyl-5-methyl-cyclohexanol)
-
-
-
SplaateCofactor,Organism,Commentary,Literature,Filename
SplaateMetals_Ions,Organism,Commentary, Literature
SplaateInhibitors, Organism, Commentary, Literature,Filename
INHIBITORS
ORGANISM
UNIPROT
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
-
SplaateActivating_Compound, Organism, Commentary, Literature,Filename
ACTIVATING COMPOUND
ORGANISM
UNIPROT
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%
SplaateKM_Value,KM_Value_Maximum, Substrate,Organism, Commentary, Literature, Filename
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
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
0.003 - 0.016
squalene
pH 6.0, 60C
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
-
SplaateTurnover_Number, Turnover_Number_Maximum, Substrate,Organism,Commentary, Literature, Filename
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.15
squalene
Alicyclobacillus acidocaldarius
-
mutant F365Y changed to O-methyltyrosine, pH 6.0, 50C
0.17
squalene
Alicyclobacillus acidocaldarius
-
mutant F365Y, pH 6.0, 50C
0.25
squalene
Alicyclobacillus acidocaldarius
-
wild-type, pH 6.0, 40C
0.27
squalene
Alicyclobacillus acidocaldarius
-
mutant F605Y, pH 6.0, 40C
0.31
squalene
Alicyclobacillus acidocaldarius
-
mutant F605W, pH 6.0, 40C
0.345
squalene
Alicyclobacillus acidocaldarius
-
pH 6.0, 45C, mutant E45A
0.353
squalene
Alicyclobacillus acidocaldarius
-
pH 6.0, 45C, mutant E93A
0.448
squalene
Alicyclobacillus acidocaldarius
-
pH 6.0, 45C, mutant R127Q
0.45
squalene
Alicyclobacillus acidocaldarius
-
mutant F605 changed to O-methyltyrosine, pH 6.0, 40C
0.54
squalene
Alicyclobacillus acidocaldarius
-
pH 6.0, 45C, mutant F434A
0.54
squalene
Alicyclobacillus acidocaldarius
-
mutant F605 changed to difluorophenylalanine plus mutation Y606A, pH 6.0, 50C
0.62
squalene
Alicyclobacillus acidocaldarius
-
pH 6.0, 45C, mutant W133A
0.64
squalene
Alicyclobacillus acidocaldarius
-
pH 6.0, 45C, mutant Y267A
0.7
squalene
Alicyclobacillus acidocaldarius
-
mutant F605Y changed to O-methyltyrosine, pH 6.0, 50C
0.735
squalene
Alicyclobacillus acidocaldarius
-
pH 6.0, 45C, mutant T41A
0.75
squalene
Alicyclobacillus acidocaldarius
-
mutant F6365 changed to trifluorophenylalanine, pH 6.0, 50C
0.82
squalene
Alicyclobacillus acidocaldarius
-
mutant F605 changed to fluorophenylalanine plus mutation Y606A, pH 6.0, 50C
0.86
squalene
Alicyclobacillus acidocaldarius
-
pH 6.0, 45C, wild-type enzyme
0.92
squalene
Alicyclobacillus acidocaldarius
-
mutant F365 changed to difluorophenylalanine, pH 6.0, 50C
1.03
squalene
Alicyclobacillus acidocaldarius
-
pH 6.0, 45C, mutant F437A
1.06
squalene
Alicyclobacillus acidocaldarius
-
pH 6.0, 45C, mutant P263G
1.09
squalene
Alicyclobacillus acidocaldarius
-
pH 6.0, 45C, mutant P263A
1.1
squalene
Alicyclobacillus acidocaldarius
-
mutant F365 changed to fluorophenylalanine, pH 6.0, 50C
1.21
squalene
Alicyclobacillus acidocaldarius
-
pH 6.0, 45C, mutant Q262A
1.32
squalene
Alicyclobacillus acidocaldarius
-
mutant F605W, pH 6.0, 50C
1.37
squalene
Alicyclobacillus acidocaldarius
-
pH 6.0, 45C, mutant Q262G
1.82
squalene
Alicyclobacillus acidocaldarius
-
mutant F605Y, pH 6.0, 50C
1.98
squalene
Alicyclobacillus acidocaldarius
-
wild-type, pH 6.0, 50C
additional information
additional information
Alicyclobacillus acidocaldarius
-
wild type and mutant enzymes
-
SplaateKCat_KM_Value,KCat_KM_Value_Maximum, Substrate,Organism, Commentary, Literature, Filename
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
3.2
squalene
Alicyclobacillus acidocaldarius
-
pH 6.0, 45C, mutant Y267A
496
4.5
squalene
Alicyclobacillus acidocaldarius
-
pH 6.0, 45C, mutant P263G
496
5.9
squalene
Alicyclobacillus acidocaldarius
-
pH 6.0, 45C, mutant P263A
496
6.6
squalene
Alicyclobacillus acidocaldarius
-
pH 6.0, 45C, mutant F434A
496
8.8
squalene
Alicyclobacillus acidocaldarius
-
pH 6.0, 45C, mutant Q262G
496
10.8
squalene
Alicyclobacillus acidocaldarius
-
pH 6.0, 45C, mutant F437A
496
11.9
squalene
Alicyclobacillus acidocaldarius
-
pH 6.0, 45C, mutant Q262A
496
16.1
squalene
Alicyclobacillus acidocaldarius
-
pH 6.0, 45C, mutant E45A
496
17.6
squalene
Alicyclobacillus acidocaldarius
-
pH 6.0, 45C, mutant R127Q
496
18.7
squalene
Alicyclobacillus acidocaldarius
-
pH 6.0, 45C, mutant E93A
496
36.7
squalene
Alicyclobacillus acidocaldarius
-
pH 6.0, 45C, mutant W133A
496
44
squalene
Alicyclobacillus acidocaldarius
-
pH 6.0, 45C, mutant T41A
496
53.09
squalene
Alicyclobacillus acidocaldarius
-
pH 6.0, 45C, wild-type enzyme
496
SplaateKI_Value,KI_Value_Maximum, Inhibitor,Organism, Commentary, Literature, Filename
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
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
-
SplaateIC50_Value,IC50_Value_Maximum, Inhibitor,Organism, Commentary, Literature, Filename
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0002
(18E)-29-methylidenehexanor-2,3-oxidosqualene
Alicyclobacillus acidocaldarius
-
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
Alicyclobacillus acidocaldarius
-
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
Alicyclobacillus acidocaldarius
-
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
Alicyclobacillus acidocaldarius
-
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
Alicyclobacillus acidocaldarius
-
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
Alicyclobacillus acidocaldarius
-
IC50 2.2 microMol, pH 6.0, 55C
-
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
0.007
(5E,9E)-13,14-epoxy-6,10,14-trimethyl-1-phenylthio-1,5,9-pentadecatriene
Alicyclobacillus acidocaldarius
-
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
Alicyclobacillus acidocaldarius
-
IC50 3 microMol, pH 6.0, 55C
-
0.000123
1-(4-(4-[(4-chloro-phenoxycarbonyl)-methyl-amino]-cyclohexyl)-benzyl)-1-hydroxy-piperidinium
Alicyclobacillus acidocaldarius
-
IC50 123 nM
0.1
3-(10'-(allylmethylamino)decanoyl)chroman-2,4-dione
Alicyclobacillus acidocaldarius
-
IC50 100 microMol
-
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
-
-
0.005
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, 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
-
0.000281
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
0.000023
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
0.2
N-dodecyliodoacetamide
Alicyclobacillus acidocaldarius
-
IC50 wild-type >200 microMol, quintuple mutant >200 microMol, sextuple mutant >200 microMol, pH 6.0, 50C
-
0.05
N-squalenyliodoacetamide
Alicyclobacillus acidocaldarius
-
IC50 sextuple mutant 50 microMol, pH 6.0, 50C
-
0.2
N-squalenyliodoacetamide
Alicyclobacillus acidocaldarius
-
IC50 quintuple mutant >200 microMol; IC50 wild-type >200 microMol
-
0.00035
Ro 48-8071
Alicyclobacillus acidocaldarius
-
IC50 0.35 microMol
SplaateSpecific_Activity, Specific_Activity_Maximum, Organism ,Commentary, Literature
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.00000227
-
crude extract
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
SplaatepH_Optimum, pH_Optimum_Maximum, Organism, Commentary, Literature
SplaatepH_Range,pH_Range_Maximum, Organism,Commentary, Literature
pH RANGE
ORGANISM
UNIPROT
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
5 - 8
-
activity range
SplaateTemperature_Optimum, Temperature_Optimum_Maximum, Organism, Commentary, Literature
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
35 - 50
-
mutant Q262G
45
-
mutant F437A; mutant F437A0
45 - 55
-
mutant Q262A
50
-
mutant E45A; mutant P263A; mutant P263G; mutant P263G, mutant P263A, mutant E45A, mutant R127Q; mutant R127Q
50 - 60
-
mutantY267A; mutant Y267A
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
SplaateTemperature_Range, Temperature_Range_Maximum, Organism, Commentary, Literature
SplaatepI_Value,pI_Value_Maximum, Organism,Commentary, Literature
SplaateSource_Tissue, Organism, Commentary, Literature, Textmining
SplaateLocalization, Organism, Commentary, id_go, Literature, Textmining
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
Alicyclobacillus acidocaldarius 104-IA, Methylococcus capsulatus Bath
-
-
-
Manually annotated by BRENDA team
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
Manually annotated by BRENDA team
SplaatePDB,PDB,PDB,Organism,Uniprot_ID
SplaateMolecular_Weight, Molecular_Weight_Maximum, Organism, Commentary, Literature
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
70000
-
SDS-PAGE
440050
72000
-
SDS-PAGE
440045, 440060
74000
-
calculated from amino acid sequence
440058
75000
-
SDS-PAGE
440057
92000
recombinant His-tagged Spterp25, SDS-PAGE
702829
150000
-
gel filtration
440052
SplaateSubunits, Organism, Commentary, Literature
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 76300, about, sequence calculation; x * 76300, SDS-PAGE
?
-
x * 74100, SDS-PAGE
?
-
x * 72300, SDS-PAGE
?
-
x * 74100, SDS-PAGE
?
-
x * 72000, SDS-PAGE
?
-
x * 74100, SDS-PAGE
dimer
-
2 * 75000, SDS-PAGE, enzyme forms aggregates in absence of detergent
homodimer
2 * 71600, about, sequence calculation
additional information
dumbbell-shaped structure of chain A with a more structured beta-barrel structure in domain 1, active site structure, structure analysis, overview; 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
SplaatePosttranslational_Modification, Organism, Commentary, Literature
SplaateCommentary, Organism, Literature
Crystallization/COMMENTARY
ORGANISM
UNIPROT
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
-
SplaatepH_Stability,pH_Stability_Maximum, Organism, Commentary, Literature
SplaateTemperature_Stability,Temperature_Stability_Maximum, Organism, Commentary, Literature
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
440045
70
-
stable for 10 min
440047
SplaateGeneral_Stability, Organism, Literature
SplaateOrganic_Solvent, Organism, Commentary, Literature
SplaateOxidation_Stability,Organism,Literature
SplaateStorage_Stability, Organism, Literature
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20C, stable for weeks
-
6C, stable for several days
-
SplaateCommentary, Organism, Literature
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ion exchange and gel filtration
-
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
wild type and mutants, homogeneity
-
SplaateCommentary, Organism, Literature
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
DNA and amino acid sequence determination and analysis, sequence comparison, expression in Escherichia coli strain DH5alpha; gene shc, DNA and amino acid sequence determination, expression in Escherichia coli
expressed in Escherichia coli
-
expression in Escherichia coli
-
expression in Escherichia coli BL21
-
expression in Escherichia coli JM 105
-
DNA and amino acid sequence determination and analysis, sequence comparison, expression in Escherichia coli strain DH5alpha
-
DNA and amino acid sequence determination and analysis, sequence comparison, expression in Escherichia coli strain DH5alpha
-
expressed in Escherichia coli BL21(DE3)pLysS cells
gene slr2089, DNA and amino acid sequence determination and analysis, sequence comparison, expression in Escherichia coli strain DH5alpha
DNA and amino acid sequence determination and analysis, sequence comparison, expression in Escherichia coli strain DH5alpha
-
gene ZMO1548, genetic organization
-
SplaateCommentary, Organism, Literature
SplaateEngineering, Organism, Commentary, Literature
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
F481C
YP3187836
site-directed mutagenesis, the mutant performs interconversion of citronellal and isopulegol
C25S/C50S/C435S/C455S/C537S
-
quintuple mutant
C25S/C50S/D376C/C435S/C455S/C537S
-
sextuple mutant
C435S/D374I/D374V/H451F
inactive mutant; site-directed mutagenesis, inactive mutant
D376E
-
10% enzyme activity
D376E
inactive mutant; site-directed mutagenesis, inactive mutant
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/D377N/Y612A
site-directed mutagenesis, the mutant shows an altered product pattern compared to the wild-type enzyme, overview; the mutant shows an altered product pattern compared to the wild-type enzyme, overview
D377C/V380E/V381A
-
no detectable cyclization of squalene
D377E
-
0.2% activity when enzyme concentration is increased to 100fold
D377E/D376Q/D376R/D377R/E45K/W406V/W417A/D377C
inactive mutant; site-directed mutagenesis, inactive mutant
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
F365A
site-directed mutagenesis, the mutant shows an altered product pattern compared to the wild-type enzyme, overview; the mutant shows an altered product pattern compared to the wild-type enzyme, overview
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
F601A
site-directed mutagenesis, the mutant shows an altered product pattern compared to the wild-type enzyme, overview; the mutant shows an altered product pattern compared to the wild-type enzyme, overview
F605A
-
altered product pattern
F605A
site-directed mutagenesis, the mutant shows an altered product pattern compared to the wild-type enzyme, overview; the mutant shows an altered product pattern compared to the wild-type enzyme, overview
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
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
-
mutation located between C29 of the hopanyl cation and the 'front water'
Q262G
-
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
Q262G/Q262A/P263G/P263A
site-directed mutagenesis, the mutant shows an altered product pattern compared to the wild-type enzyme, overview; the mutant shows an altered product pattern compared to the wild-type enzyme, overview
R127Q
-
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
-
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
V380E
inactive mutant; site-directed mutagenesis, inactive mutant
V381A/D376C
inactive mutant; site-directed mutagenesis, inactive mutant
W133A
-
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
W169F/W169H/W489A/F605K
site-directed mutagenesis, the mutant shows an altered product pattern compared to the wild-type enzyme, overview; the mutant shows an altered product pattern compared to the wild-type enzyme, overview
W23V
-
same activity and optimal temperature as wild type enzyme
W258L
-
60% of wild type activity, lower temperature optimum
W406V
-
no enzyme activity
W417A
-
no enzyme activity
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
-
mutation near the substrat channel; production of hop-22(29)-ene is decreased, production of hopanol is markedly increased at lower temperatures
Y420A
site-directed mutagenesis, the mutant shows an altered product pattern compared to the wild-type enzyme, overview; 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
Y495F
-
reduced enzyme activity, wild-type product pattern
Y606A
-
kinetics identical to wild-type
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; 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; the mutant shows an altered product pattern compared to the wild-type enzyme, overview
Y609F
-
wild type activity, altered product pattern
Y609F
site-directed mutagenesis, the mutant shows an altered product pattern compared to the wild-type enzyme, overview; 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; the mutant shows an altered product pattern compared to the wild-type enzyme, overview
Y612F
-
reduced enzyme activity, wild-type product pattern
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; the mutant shows the same product pattern as the wild-type with less enzyme activity
Y420C
Alicyclobacillus acidocaldarius DSM 446
-
site-directed mutagenesis, the mutant performs interconversion of citronellal and isopulegol
-
F409C
site-directed mutagenesis, the mutant does not perform interconversion of citronellal and isopulegol
F447C
-
site-directed mutagenesis, the mutant performs interconversion of citronellal and isopulegol
F436C
site-directed mutagenesis, the mutant does not perform interconversion of citronellal and isopulegol
F450C
site-directed mutagenesis, the mutant does not perform interconversion of citronellal and isopulegol
F436C
Burkholderia ambifaria ATCC BAA-244/AMMD
-
site-directed mutagenesis, the mutant does not perform interconversion of citronellal and isopulegol
-
F450C
Burkholderia ambifaria ATCC BAA-244/AMMD
-
site-directed mutagenesis, the mutant does not perform interconversion of citronellal and isopulegol
-
F445C
-
site-directed mutagenesis, the mutant does not perform interconversion of citronellal and isopulegol
F457C
site-directed mutagenesis, the mutant does not perform interconversion of citronellal and isopulegol
F438C
-
site-directed mutagenesis, the mutant does not perform interconversion of citronellal and isopulegol
F438C
site-directed mutagenesis, the mutant performs interconversion of citronellal and isopulegol
F486C
site-directed mutagenesis, the mutant shows increased activity in interconversion of citronellal and isopulegol compared to the wild-type enzyme
W555A
site-directed mutagenesis, the mutant shows no squalene hopene cyclase activity, and low citronellal cyclase activity
W555C
site-directed mutagenesis, the mutant shows no squalene hopene cyclase activity, and low citronellal cyclase activity
W555D
site-directed mutagenesis, the mutant shows no squalene hopene cyclase activity, and moderate citronellal cyclase activity
W555E
site-directed mutagenesis, the mutant shows highly reduced squalene hopene cyclase activity, and low citronellal cyclase activity
W555F
site-directed mutagenesis, the mutant shows no squalene hopene cyclase activity, and higher citronellal cyclase activity; W555 is essential for hopene formation but W555Y and W555F have enhanced citronellal cyclase activity. All muteins of position W555 show abolished or strongly reduced hopene-forming activity compared to wild-type protein. W555Y is the only mutein with low but significant residual SHC activity
W555G
site-directed mutagenesis, the mutant shows no squalene hopene cyclase activity, and low citronellal cyclase activity
W555H
site-directed mutagenesis, the mutant shows no squalene hopene cyclase activity, and moderate citronellal cyclase activity
W555I
site-directed mutagenesis, the mutant shows no squalene hopene cyclase activity, and low citronellal cyclase activity
W555K
site-directed mutagenesis, the mutant shows no squalene hopene cyclase activity, and low citronellal cyclase activity
W555L
site-directed mutagenesis, the mutant shows no squalene hopene cyclase activity, and low citronellal cyclase activity
W555M
site-directed mutagenesis, the mutant shows highly reduced squalene hopene cyclase activity, and low citronellal cyclase activity
W555N
site-directed mutagenesis, the mutant shows highly reduced squalene hopene cyclase activity, and moderate citronellal cyclase activity
W555P
site-directed mutagenesis, the mutant shows no squalene hopene cyclase activity, and low citronellal cyclase activity
W555Q
site-directed mutagenesis, the mutant shows highly reduced squalene hopene cyclase activity, and low citronellal cyclase activity
W555R
site-directed mutagenesis, the mutant shows no squalene hopene cyclase activity, and low citronellal cyclase activity
W555S
site-directed mutagenesis, the mutant shows no squalene hopene cyclase activity, and low citronellal cyclase activity
W555T
site-directed mutagenesis, the mutant shows no squalene hopene cyclase activity, and higher citronellal cyclase activity
W555V
site-directed mutagenesis, the mutant shows no squalene hopene cyclase activity, and low citronellal cyclase activity
W555Y
site-directed mutagenesis, the mutant shows highly reduced squalene hopene cyclase activity,and higher citronellal cyclase activity; W555 is essential for hopene formation but W555Y and W555F have enhanced citronellal cyclase activity. All muteins of position W555 show abolished or strongly reduced hopene-forming activity compared to wild-type protein. W555Y is the only mutein with low but significant residual SHC activity
F438C
Zymomonas mobilis ZMO-0872
-
site-directed mutagenesis, the mutant performs interconversion of citronellal and isopulegol
-
F486C
Zymomonas mobilis ZMO-1548
-
site-directed mutagenesis, the mutant shows increased activity in interconversion of citronellal and isopulegol compared to the wild-type enzyme
-
W555F
Zymomonas mobilis ZMO-1548
-
site-directed mutagenesis, the mutant shows no squalene hopene cyclase activity, and higher citronellal cyclase activity; W555 is essential for hopene formation but W555Y and W555F have enhanced citronellal cyclase activity. All muteins of position W555 show abolished or strongly reduced hopene-forming activity compared to wild-type protein. W555Y is the only mutein with low but significant residual SHC activity
-
W555Y
Zymomonas mobilis ZMO-1548
-
site-directed mutagenesis, the mutant shows highly reduced squalene hopene cyclase activity,and higher citronellal cyclase activity; W555 is essential for hopene formation but W555Y and W555F have enhanced citronellal cyclase activity. All muteins of position W555 show abolished or strongly reduced hopene-forming activity compared to wild-type protein. W555Y is the only mutein with low but significant residual SHC activity
-
I261A
site-directed mutagenesis, the mutant shows an altered product pattern compared to the wild-type enzyme, overview; the mutant shows an altered product pattern compared to the wild-type enzyme, overview
additional information
-
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
-
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
additional information
product patterns of mutant enzymes, detailed overview
F438C
site-directed mutagenesis, the mutant does not perform interconversion of citronellal and isopulegol
additional information
knockout of gene slr2089, phenotype and self-complementation by gene slr2089 expression
SplaateCommentary, Organism, Literature
SplaateApplication,Organism,Commentary,Literature
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
synthesis
-
production of unnatural polyprenoids and supranatural steroids by manipulation of the enzyme reaction by combination of substrate analogues
synthesis
it is possible to use the cyanobacterium Synechocystis to generate squalene, a hydrocarbon of commercial interest and a potential biofuel
synthesis
-
cyclization of homofarnesol to ambroxan as well as the conversion of citronellal to 2-isopropenyl-5-methyl-cyclohexanol bythe isozyme SHC1 can be economically attractive, as both products are used in the flavour and fragrance industry