BRENDA - Enzyme Database show
show all sequences of 1.1.1.270

The functions of key residues in the inhibitor, substrate and cofactor sites of human 3beta-hydroxysteroid dehydrogenase type 1 are validated by mutagenesis

Thomas, J.L.; Mack, V.L.; Sun, J.; Terrell, J.R.; Bucholtz, K.M.; J. Steroid Biochem. Mol. Biol. 120, 192-199 (2010)

Data extracted from this reference:

Application
Application
Commentary
Organism
medicine
the selective inhibition of human 3beta-HSD1 in breast tumors represents a potential treatment for hormone-sensitive breast cancer
Homo sapiens
Cloned(Commentary)
Commentary
Organism
expression of wild-type and mutant enzymes in Spodoptera frugiperda Sf9 cells using the baculovirus transfection system
Homo sapiens
Engineering
Amino acid exchange
Commentary
Organism
D61N
site-directed mutagenesis, mutation in isozyme 3beta-HSD1
Homo sapiens
D61V
site-directed mutagenesis, mutation in isozyme 3beta-HSD1
Homo sapiens
E192A
site-directed mutagenesis, mutation in isozyme 3beta-HSD1
Homo sapiens
P195R
site-directed mutagenesis, mutation in isozyme 3beta-HSD2
Homo sapiens
R195P
site-directed mutagenesis, mutation in isozyme 3beta-HSD1
Homo sapiens
T8A
site-directed mutagenesis, mutation in isozyme 3beta-HSD1
Homo sapiens
Inhibitors
Inhibitors
Commentary
Organism
Structure
trilostane
competitive for 3beta-HSD1, noncompetitive for 3beta-HSD2
Homo sapiens
Organism
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
Homo sapiens
-
-
-
Purification (Commentary)
Commentary
Organism
recombinant wild-type and mutant enzymes from Sf9 insect cells by ultracentrifugation
Homo sapiens
Source Tissue
Source Tissue
Commentary
Organism
Textmining
breast cancer cell
selective expression of 3beta-HSD1
Homo sapiens
-
mammary gland
selective expression of 3beta-HSD1
Homo sapiens
-
additional information
isozymes 3beta-HSD1 and 3beta-HSD2 are encoded by two distinct genes which are expressed in a tissue-specific pattern
Homo sapiens
-
placenta
selective expression of 3beta-HSD1
Homo sapiens
-
Substrates and Products (Substrate)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
16alpha-hydroxy-dehydroepiandrosterone + NADH + H+
-
725813
Homo sapiens
?
-
-
-
?
16beta-hydroxy-dehydroepiandrosterone + NADH + H+
-
725813
Homo sapiens
?
-
-
-
?
17alpha-hydroxypregnenolone + NADH + H+
-
725813
Homo sapiens
17alpha-hydroxyprogesterone + NAD+
-
-
-
?
5-androstene-3,17-dione + NAD+
-
725813
Homo sapiens
dehydroepiandrosterone + NADH + H+
-
-
-
?
dehydroepiandrosterone + NADH + H+
-
725813
Homo sapiens
5-androstene-3,17-dione + NAD+
-
-
-
?
additional information
both isoforms of the enzyme catalyze the conversion of 3beta-hydroxy-5-ene-steroids (dehydroepiandrosterone, 17alpha-hydroxypregnenolone, pregnenolone) to 3-oxo-4-ene-steroids (androstenedione, 17alpha-hydroxyprogestrone, progesterone) on a single, dimeric protein containing both enzyme activities
725813
Homo sapiens
?
-
-
-
-
pregnenolone + NADH + H+
-
725813
Homo sapiens
progesterone + NAD+
-
-
-
?
Temperature Optimum [°C]
Temperature Optimum [°C]
Temperature Optimum Maximum [°C]
Commentary
Organism
27
-
assay at
Homo sapiens
pH Optimum
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
7.4
-
assay at
Homo sapiens
Cofactor
Cofactor
Commentary
Organism
Structure
NAD+
-
Homo sapiens
NADH
-
Homo sapiens
Ki Value [mM]
Ki Value [mM]
Ki Value maximum [mM]
Inhibitor
Commentary
Organism
Structure
0.0001
-
trilostane
3beta-HSD1 wild-type, pH 7.4, 27°C
Homo sapiens
0.00019
-
trilostane
3beta-HSD2 mutant P195R, pH 7.4, 27°C
Homo sapiens
0.0016
-
trilostane
3beta-HSD2 wild-type, pH 7.4, 27°C
Homo sapiens
0.00256
-
trilostane
3beta-HSD1 mutant R195P, pH 7.4, 27°C
Homo sapiens
Application (protein specific)
Application
Commentary
Organism
medicine
the selective inhibition of human 3beta-HSD1 in breast tumors represents a potential treatment for hormone-sensitive breast cancer
Homo sapiens
Cloned(Commentary) (protein specific)
Commentary
Organism
expression of wild-type and mutant enzymes in Spodoptera frugiperda Sf9 cells using the baculovirus transfection system
Homo sapiens
Cofactor (protein specific)
Cofactor
Commentary
Organism
Structure
NAD+
-
Homo sapiens
NADH
-
Homo sapiens
Engineering (protein specific)
Amino acid exchange
Commentary
Organism
D61N
site-directed mutagenesis, mutation in isozyme 3beta-HSD1
Homo sapiens
D61V
site-directed mutagenesis, mutation in isozyme 3beta-HSD1
Homo sapiens
E192A
site-directed mutagenesis, mutation in isozyme 3beta-HSD1
Homo sapiens
P195R
site-directed mutagenesis, mutation in isozyme 3beta-HSD2
Homo sapiens
R195P
site-directed mutagenesis, mutation in isozyme 3beta-HSD1
Homo sapiens
T8A
site-directed mutagenesis, mutation in isozyme 3beta-HSD1
Homo sapiens
Inhibitors (protein specific)
Inhibitors
Commentary
Organism
Structure
trilostane
competitive for 3beta-HSD1, noncompetitive for 3beta-HSD2
Homo sapiens
Ki Value [mM] (protein specific)
Ki Value [mM]
Ki Value maximum [mM]
Inhibitor
Commentary
Organism
Structure
0.0001
-
trilostane
3beta-HSD1 wild-type, pH 7.4, 27°C
Homo sapiens
0.00019
-
trilostane
3beta-HSD2 mutant P195R, pH 7.4, 27°C
Homo sapiens
0.0016
-
trilostane
3beta-HSD2 wild-type, pH 7.4, 27°C
Homo sapiens
0.00256
-
trilostane
3beta-HSD1 mutant R195P, pH 7.4, 27°C
Homo sapiens
Purification (Commentary) (protein specific)
Commentary
Organism
recombinant wild-type and mutant enzymes from Sf9 insect cells by ultracentrifugation
Homo sapiens
Source Tissue (protein specific)
Source Tissue
Commentary
Organism
Textmining
breast cancer cell
selective expression of 3beta-HSD1
Homo sapiens
-
mammary gland
selective expression of 3beta-HSD1
Homo sapiens
-
additional information
isozymes 3beta-HSD1 and 3beta-HSD2 are encoded by two distinct genes which are expressed in a tissue-specific pattern
Homo sapiens
-
placenta
selective expression of 3beta-HSD1
Homo sapiens
-
Substrates and Products (Substrate) (protein specific)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
16alpha-hydroxy-dehydroepiandrosterone + NADH + H+
-
725813
Homo sapiens
?
-
-
-
?
16beta-hydroxy-dehydroepiandrosterone + NADH + H+
-
725813
Homo sapiens
?
-
-
-
?
17alpha-hydroxypregnenolone + NADH + H+
-
725813
Homo sapiens
17alpha-hydroxyprogesterone + NAD+
-
-
-
?
5-androstene-3,17-dione + NAD+
-
725813
Homo sapiens
dehydroepiandrosterone + NADH + H+
-
-
-
?
dehydroepiandrosterone + NADH + H+
-
725813
Homo sapiens
5-androstene-3,17-dione + NAD+
-
-
-
?
additional information
both isoforms of the enzyme catalyze the conversion of 3beta-hydroxy-5-ene-steroids (dehydroepiandrosterone, 17alpha-hydroxypregnenolone, pregnenolone) to 3-oxo-4-ene-steroids (androstenedione, 17alpha-hydroxyprogestrone, progesterone) on a single, dimeric protein containing both enzyme activities
725813
Homo sapiens
?
-
-
-
-
pregnenolone + NADH + H+
-
725813
Homo sapiens
progesterone + NAD+
-
-
-
?
Temperature Optimum [°C] (protein specific)
Temperature Optimum [°C]
Temperature Optimum Maximum [°C]
Commentary
Organism
27
-
assay at
Homo sapiens
pH Optimum (protein specific)
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
7.4
-
assay at
Homo sapiens
General Information
General Information
Commentary
Organism
evolution
human 3beta-hydroxysteroid dehydrogenase is a member of the short-chain dehydrogenase/reductase (SDR) family of enzymes, all of which contain the Rossmann-fold domain with a beta-alpha-beta-alpha-beta-alpha-beta-alpha-beta folding pattern that binds cofactor and substrate
Homo sapiens
metabolism
the enzyme catalyzes the first step in the conversion of dehydroepiandrosterone to estradiol
Homo sapiens
physiological function
the enzyme promotes tumor growth in placenta, mammary glands, and breasts. In human adrenals, 3beta-HSD2 is required for the production of cortisol and aldosterone
Homo sapiens
General Information (protein specific)
General Information
Commentary
Organism
evolution
human 3beta-hydroxysteroid dehydrogenase is a member of the short-chain dehydrogenase/reductase (SDR) family of enzymes, all of which contain the Rossmann-fold domain with a beta-alpha-beta-alpha-beta-alpha-beta-alpha-beta folding pattern that binds cofactor and substrate
Homo sapiens
metabolism
the enzyme catalyzes the first step in the conversion of dehydroepiandrosterone to estradiol
Homo sapiens
physiological function
the enzyme promotes tumor growth in placenta, mammary glands, and breasts. In human adrenals, 3beta-HSD2 is required for the production of cortisol and aldosterone
Homo sapiens
Other publictions for EC 1.1.1.270
No.
1st author
Pub Med
title
organims
journal
volume
pages
year
Activating Compound
Application
Cloned(Commentary)
Crystallization (Commentary)
Engineering
General Stability
Inhibitors
KM Value [mM]
Localization
Metals/Ions
Molecular Weight [Da]
Natural Substrates/ Products (Substrates)
Organic Solvent Stability
Organism
Oxidation Stability
Posttranslational Modification
Purification (Commentary)
Reaction
Renatured (Commentary)
Source Tissue
Specific Activity [micromol/min/mg]
Storage Stability
Substrates and Products (Substrate)
Subunits
Temperature Optimum [°C]
Temperature Range [°C]
Temperature Stability [°C]
Turnover Number [1/s]
pH Optimum
pH Range
pH Stability
Cofactor
Ki Value [mM]
pI Value
IC50 Value
Activating Compound (protein specific)
Application (protein specific)
Cloned(Commentary) (protein specific)
Cofactor (protein specific)
Crystallization (Commentary) (protein specific)
Engineering (protein specific)
General Stability (protein specific)
IC50 Value (protein specific)
Inhibitors (protein specific)
Ki Value [mM] (protein specific)
KM Value [mM] (protein specific)
Localization (protein specific)
Metals/Ions (protein specific)
Molecular Weight [Da] (protein specific)
Natural Substrates/ Products (Substrates) (protein specific)
Organic Solvent Stability (protein specific)
Oxidation Stability (protein specific)
Posttranslational Modification (protein specific)
Purification (Commentary) (protein specific)
Renatured (Commentary) (protein specific)
Source Tissue (protein specific)
Specific Activity [micromol/min/mg] (protein specific)
Storage Stability (protein specific)
Substrates and Products (Substrate) (protein specific)
Subunits (protein specific)
Temperature Optimum [°C] (protein specific)
Temperature Range [°C] (protein specific)
Temperature Stability [°C] (protein specific)
Turnover Number [1/s] (protein specific)
pH Optimum (protein specific)
pH Range (protein specific)
pH Stability (protein specific)
pI Value (protein specific)
Expression
General Information
General Information (protein specific)
Expression (protein specific)
KCat/KM [mM/s]
KCat/KM [mM/s] (protein specific)
740936
Ferrante
4-Methylzymosterone and other ...
Saccharomyces cerevisiae
Lipids
51
1103-1113
2016
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741250
Chen
Metabolism of androstenone, 17 ...
Sus scrofa
PLoS ONE
10
e113194
2015
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726098
Debieu
Role of sterol 3-ketoreductase ...
Botrytis cinerea
Pest Manag. Sci.
69
642-651
2013
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5
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2
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740097
Layer
Characterization of a mutation ...
Mus musculus
Biochim. Biophys. Acta
1831
361-369
2013
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1
1
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724124
Endo
Characterization of rabbit ald ...
Oryctolagus cuniculus
Arch. Biochem. Biophys.
527
23-30
2012
-
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1
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4
-
14
20
1
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1
1
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3
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1
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6
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27
-
1
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21
1
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2
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14
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1
2
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4
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14
14
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20
1
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1
1
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1
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6
-
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27
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1
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21
1
-
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3
3
-
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702462
Taramino
Interactions of oxidosqualene ...
Saccharomyces cerevisiae
Biochim. Biophys. Acta
1801
156-162
2010
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1
1
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711300
Taramino
Divergent interactions involvi ...
Homo sapiens, Mus musculus
Biochim. Biophys. Acta
1801
1232-1237
2010
-
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2
-
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7
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1
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1
1
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725813
Thomas
The functions of key residues ...
Homo sapiens
J. Steroid Biochem. Mol. Biol.
120
192-199
2010
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1
1
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6
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1
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2
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1
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6
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6
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1
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7
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1
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1
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3
3
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673822
Tam
Activities of 3beta-HSD and ar ...
Taeniopygia guttata
Gen. Comp. Endocrinol.
150
26-33
2006
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675595
Steckelbroeck
Tibolone metabolism in human l ...
Homo sapiens
J. Pharmacol. Exp. Ther.
316
1300-1309
2006
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677144
Jin
Molecular docking simulations ...
Homo sapiens
Steroids
71
380-391
2006
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656200
Steckelbroeck
Human cytosolic 3alpha-hydroxy ...
Homo sapiens
J. Biol. Chem.
279
10784-10795
2004
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3
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655348
Rizner
Human type 3 3alpha-hydroxyste ...
Homo sapiens
Endocrinology
144
2922-2932
2003
-
-
-
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1
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1
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1
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656795
Marijanovic
Closing the gap: Identificatio ...
Homo sapiens, Mus musculus
Mol. Endocrinol.
17
1715-1725
2003
-
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2
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1
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2
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2
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5
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5
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4
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2
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2
2
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1
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5
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4
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723672
Mo
Protein-protein interactions a ...
Saccharomyces cerevisiae
Proc. Natl. Acad. Sci. USA
99
39-44
2002
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286477
Huang
Gene structure, chromosomal lo ...
Homo sapiens
Biochim. Biophys. Acta
1520
124-130
2001
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1
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3
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3
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1
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-
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-
-
-
-
-
-
-
-
-
-
-
-
-
286474
Pascal
Plant sterol biosynthesis: ide ...
Zea mays
Arch. Biochem. Biophys.
312
260-271
1994
1
-
-
-
-
-
2
11
2
-
-
2
-
3
-
-
-
1
-
2
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27
-
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27
-
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-
-
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-
-
-
-
-
-
-
-
286476
Vanden Bossche
Effects of itraconazole on cyt ...
Cryptococcus neoformans
Antimicrob. Agents Chemother.
37
2101-2105
1993
-
-
-
-
-
-
1
-
-
-
-
1
-
5
-
-
-
-
-
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3
-
-
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-
-
-
-
-
-
-
-
-
-
-
286478
De Launoit
Expression of liver-specific m ...
Rattus norvegicus
J. Biol. Chem.
267
4513-4517
1992
-
-
1
-
-
-
1
1
-
-
-
2
-
3
-
-
-
-
-
1
-
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11
-
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-
-
11
-
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-
-
-
1
-
-
-
-
-
-
-
-
-
286473
Appelkvist
Presence of individual enzymes ...
Rattus norvegicus
Arch. Biochem. Biophys.
282
318-325
1990
1
-
-
-
-
-
-
-
4
-
-
2
-
2
-
-
-
-
-
1
-
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-
1
-
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-
-
3
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
286472
Billheimer
Solubilization and partial pur ...
Rattus norvegicus
Arch. Biochem. Biophys.
211
430-438
1981
2
1
-
-
-
4
2
2
2
-
1
3
-
1
-
-
1
-
-
1
1
-
7
-
1
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-
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1
-
7
-
1
-
-
-
1
-
-
-
-
-
-
-
-
-
286475
Wieland
A DNA-binding of mouse kidney ...
Mus musculus
Steroids
37
527-538
1981
-
-
-
-
-
-
-
-
2
-
-
1
-
2
-
-
-
-
-
4
-
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-
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