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Information on EC 1.1.1.146 - 11beta-hydroxysteroid dehydrogenase and Organism(s) Cavia porcellus and UniProt Accession Q6QLL4

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Cavia porcellus
UNIPROT: Q6QLL4 not found.
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The taxonomic range for the selected organisms is: Cavia porcellus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Synonyms
11beta-hsd1, 11beta-hsd2, hsd11b2, hsd11b1, 11beta-hydroxysteroid dehydrogenase, 11beta-hsd, 11beta-hydroxysteroid dehydrogenase type 1, 11betahsd2, beta-hydroxysteroid dehydrogenase, 11betahsd1, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
11beta-HSD1
-
11beta-hydroxysteroid dehydrogenase type 1
-
11-beta-HSD1
-
-
-
-
11-beta-HSD2
-
-
-
-
11-DH
-
-
-
-
11-DH2
-
-
-
-
11beta-HSD1
-
-
11beta-HSD1A
-
-
-
-
11beta-hydroxy steroid dehydrogenase
-
-
-
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11beta-hydroxysteroid dehydrogenase type 1
-
-
beta-hydroxysteroid dehydrogenase
-
-
-
-
corticosteroid 11-reductase
-
-
-
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corticosteroid 11beta-dehydrogenase
-
-
-
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dehydrogenase, 11beta-hydroxy steroid
-
-
-
-
NAD-dependent 11-beta-hydroxysteroid dehydrogenase
-
-
-
-
type 1 11beta-hydroxysteroid dehydrogenase
-
-
additional information
-
the enzyme belongs to the short-chain dehydrogenase/reductase superfamily
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
an 11beta-hydroxysteroid + NADP+ = an 11-oxosteroid + NADPH + H+
show the reaction diagram
active site variability of isozyme 11beta-HSD1, structure-activity analysis, catalytic mechanism
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
redox reaction
-
-
-
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oxidation
-
-
-
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reduction
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
11beta-hydroxysteroid:NADP+ 11-oxidoreductase
-
CAS REGISTRY NUMBER
COMMENTARY hide
9041-46-7
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
cortisone + NADPH + H+
cortisol + NADP+
show the reaction diagram
isozyme 11beta-HSD1 catalyzes the forward reaction with cofactor NADPH
-
-
ir
1,2-dehydrocortisone + NADPH
1,2-dehydrocortisol + NADP+
show the reaction diagram
-
-
-
-
r
11-oxo-progesterone + NADPH + H+
11beta-hydroxyprogesterone + NADP+
show the reaction diagram
-
-
-
-
r
11beta,21-dihydroxypregn-4-en-3,20-dione + NADP+
21-hydroxy-pregn-4-en-3,11,20-trione + NADPH + H+
show the reaction diagram
-
-
-
?
16alpha-methyl-1,2-dehydrocortisone + NADPH
16alpha-methyl-1,2-dehydrocortisol + NADP+
show the reaction diagram
-
-
-
-
r
16alpha-methylcortisone + NADPH
16alpha-methylcortisol + NADP+
show the reaction diagram
-
-
-
-
r
17,21-dihydroxy-pregn-4-ene-3,11,20-trione + NADPH
11beta,17,21-trihydroxy-pregn-4-ene-3,20-dione + NADP+
show the reaction diagram
-
i.e. cortisone
i.e. cortisol
?
21-hydroxy-pregn-4-en-3,11,20-trione + NADPH
11beta,21-dihydroxypregn-4-en-3,20-dione + NADP+
show the reaction diagram
-
-
i.e. corticosterone
?
9alpha-fluorocortisone + NADPH
9alpha-fluorocortisol + NADP+
show the reaction diagram
-
-
-
-
r
androst-4-ene-3,11,17-trione + NADPH
11beta-hydroxyandrost-4-ene-3,17-dione + NADP+
show the reaction diagram
-
-
-
r
corticosterone + NADPH + H+
corticosterol + NADP+
show the reaction diagram
-
-
-
-
r
cortisone + NAD(P)H
cortisol + NAD(P)+
show the reaction diagram
-
-
-
-
r
cortisone + NADPH + H+
cortisol + NADP+
show the reaction diagram
-
-
-
-
r
pregn-4-ene-3,11,20-trione + NADPH
11beta-hydroxy-pregn-4-ene-3,20-dione + NADP+
show the reaction diagram
-
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
cortisone + NADPH + H+
cortisol + NADP+
show the reaction diagram
isozyme 11beta-HSD1 catalyzes the forward reaction with cofactor NADPH
-
-
ir
11beta,21-dihydroxypregn-4-en-3,20-dione + NADP+
21-hydroxy-pregn-4-en-3,11,20-trione + NADPH + H+
show the reaction diagram
-
-
-
?
17,21-dihydroxy-pregn-4-ene-3,11,20-trione + NADPH
11beta,17,21-trihydroxy-pregn-4-ene-3,20-dione + NADP+
show the reaction diagram
-
i.e. cortisone
i.e. cortisol
?
21-hydroxy-pregn-4-en-3,11,20-trione + NADPH
11beta,21-dihydroxypregn-4-en-3,20-dione + NADP+
show the reaction diagram
-
-
i.e. corticosterone
?
cortisone + NAD(P)H
cortisol + NAD(P)+
show the reaction diagram
-
-
-
-
r
cortisone + NADPH + H+
cortisol + NADP+
show the reaction diagram
-
-
-
-
r
pregn-4-ene-3,11,20-trione + NADPH
11beta-hydroxy-pregn-4-ene-3,20-dione + NADP+
show the reaction diagram
-
-
-
?
additional information
?
-
-
the enzyme activates pro-glucocorticoid hormones in a tissue-specific manner
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NAD+
-
NADP+ is the preferred cofactor, low activity with NAD+
NADH
-
NADPH is the preferred cofactor, low activity with NADH
NADP+
NADPH
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
EDTA does not affect enzyme activity
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
4-chloromercuribenzoate
-
complete inhibition of cortisol oxidation at 0.01 mM
9alpha-Fluorocortisol
-
a competitive inhibitor of the oxidation of cortisol
arylsulfoamidothiazole
-
-
arylsulfoamidothiazoles
-
weak or not binding inhibitors, inhibition mode and profiles
-
carbenoxolone
-
unspecific inhibitor
glycyrrhizic acid
-
dose-dependent competitive inhibition, IC50: 1.994 mM
gossypol acetic acid
-
dose-dependent competitive inhibition, IC50: 0.297 mM, (+)-isomer more potent inhibitor than (-)-isomer, mutant hairless strain more sensitive to inhibition than haired strain due to pharmacogenetic differences between the strains
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.075
1,2-dehydrocortisol
-
-
0.027
11beta,17,21-trihydroxy-pregn-4-ene-3,20-dione
-
-
0.0027 - 0.0195
11beta,21-dihydroxypregn-4-en-3,20-dione
0.0169
11beta-hydroxyprogesterone
-
-
0.204
16alpha-methyl-1,2-dehydrocortisol
-
-
0.0487
16alpha-Methylcortisol
-
-
0.003
cortisol
-
37°C, pH 7.4, recombinant 11beta-HSD1 expressed in Escherichia coli
0.00028 - 0.008
cortisone
additional information
additional information
-
substrate specificity and kinetics
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.04
cortisol
-
37°C, pH 7.4, recombinant 11beta-HSD1 expressed in Escherichia coli
0.3
cortisone
-
37°C, pH 7.4, recombinant 11beta-HSD1 expressed in Escherichia coli
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.003
arylsulfoamidothiazole
-
above
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1.994
glycyrrhizic acid
Cavia porcellus
-
dose-dependent competitive inhibition, IC50: 1.994 mM
0.297
gossypol acetic acid
Cavia porcellus
-
dose-dependent competitive inhibition, IC50: 0.297 mM, (+)-isomer more potent inhibitor than (-)-isomer, mutant hairless strain more sensitive to inhibition than haired strain due to pharmacogenetic differences between the strains
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.00021
-
oxidation of cortisol
0.00045
-
reduction of cortisone
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.5
-
cortisone reduction
9.5
-
cortisol oxidation
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
pH profile of forward and reverse reaction
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
18 - 20
-
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
the active site of isozyme 11beta-HSD1 is located on the lumen side
Manually annotated by BRENDA team
-
isozyme 11beta-HSD1 is anchored through an N-terminal transmembrane domain
Manually annotated by BRENDA team
additional information
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
DHI1_CAVPO
300
1
33226
Swiss-Prot
Secretory Pathway (Reliability: 1)
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
comparison of primary structures, three-dimensional structure around the substrate binding site, and active site amino acid sequences of several mammalia
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified recombinant isozyme 11beta-HSD1 in complex with substrate, cofactor and analogue, or inhibitor, 10 mg/ml protein in 20 mM Tris-HCl, pH 8.0, 2mM Tris(carboxyethyl)phosphine, 5% glycerol, 0.5 M guanidinum hydrochloride, 0.05% Anapoe X-100, 0.02 mM cortisone, and 0.04 mM NADP+ analogue 3-aminopyridine adenine dinucleotide phosphate AADP, NADP+, BVT-4584, or cortisone, hanging drop vapour diffusion method, mixing with equal volume of precipitation solution containing 38-40% PEG 550 mono methyl ether, and 0.1 M Bis-Tris, pH 6.5, equlibration against 1 ml precipitation solution, 5-6 days, X-ray diffraction structure determination and analysis at 2.5 A resolution
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-15°C, purified microsomes stored as frozen pellets, retain their ability to oxidize cortisol to cortisone with little loss in activity over several months, their ability to reduce cortisone to cortisol declines fairly rapidly to 30% of maximal activity within 30 days, the stability of acetone-dried powders of washed microsomes is high, and oxidizing activity is stable for 3 months, reducing activity for up to 2 months
-
-70°C, 0.01 M sodium phosphate, pH 7.0, 0.25 M sucrose, 6 weeks
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His6-tagged isozyme 11beta-HSD1 from Escherichia coli strain BL21(DE3) by metal affinity chromatography
native enzyme from liver microsomes partially by microsome preparation
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of His6-tagged isozyme 11beta-HSD1 in Escherichia coli strain BL21(DE3)
expression of 11beta-HSD1 in Pichia pastoris, COS cells and Escherichia coli
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Sang, G.W.; Lorenzo, B.; Reidenberg, M.M.
Inhibitory effects of gossypol on corticosteroid 11beta-hydroxysteroid dehydrogenase from guinea pig kidney: A possible mechanism for causing hypokalemia
J. Steroid Biochem. Mol. Biol.
39
169-176
1991
Cavia porcellus
Manually annotated by BRENDA team
Bush, I.E.; Hunter, S.A.; Meigs, R.A.
Metabolism of 11-oxogenated steroids. Metabolism in vitro by preparations of liver
Biochem. J.
107
239-258
1968
Bos taurus, Cavia porcellus, Oryctolagus cuniculus, Rattus norvegicus, Rattus sp.
Manually annotated by BRENDA team
Shafqat, N.; Elleby, B.; Svensson, S.; Shafqat, J.; Jornvall, H.; Abrahmsen, L.; Oppermann, U.
Comparative enzymology of 11beta -hydroxysteroid dehydrogenase type 1 from glucocorticoid resistant (guinea pig) versus sensitive (human) species
J. Biol. Chem.
278
2030-2035
2003
Cavia porcellus, Homo sapiens
Manually annotated by BRENDA team
Ogg, D.; Elleby, B.; Norstroem, C.; Stefansson, K.; Abrahmsen, L.; Oppermann, U.; Svensson, S.
The crystal structure of guinea pig 11beta-hydroxysteroid dehydrogenase type 1 provides a model for enzyme-lipid bilayer interactions
J. Biol. Chem.
280
3789-3794
2005
Cavia porcellus (Q6QLL4), Cavia porcellus
Manually annotated by BRENDA team
Hult, M.; Shafqat, N.; Elleby, B.; Mitschke, D.; Svensson, S.; Forsgren, M.; Barf, T.; Vallgarda, J.; Abrahmsen, L.; Oppermann, U.
Active site variability of type 1 11beta-hydroxysteroid dehydrogenase revealed by selective inhibitors and cross-species comparisons
Mol. Cell. Endocrinol.
248
26-33
2006
Cavia porcellus, Mus musculus, Rattus norvegicus, Homo sapiens (P28845), Homo sapiens
Manually annotated by BRENDA team