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1.1.1.146: 11beta-hydroxysteroid dehydrogenase

This is an abbreviated version!
For detailed information about 11beta-hydroxysteroid dehydrogenase, go to the full flat file.

Word Map on EC 1.1.1.146

Reaction

an 11beta-hydroxysteroid
+
NADP+
=
an 11-oxosteroid
 +
NADPH
 +
H+

Synonyms

11 beta-hydroxysteroid dehydrogenase type 1, 11-beta hydroxysteroid dehydrogenase type 1, 11-beta-HSD1, 11-beta-HSD1 (oxidase) NADP+, 11-beta-HSD2, 11-beta-hydroxysteroid dehydrogenase type1, 11-DH, 11-DH2, 11-oxoreductase, 11beta hydroxysteroid dehydrogenase type 1, 11beta-HSD, 11beta-HSD 1, 11beta-HSD type 1, 11beta-HSD-1, 11beta-HSD-2, 11beta-HSD1, 11beta-HSD1A, 11beta-HSD2, 11beta-hydroxy steroid dehydrogenase, 11beta-hydroxy steroid dehydrogenase type 2, 11beta-hydroxysteroid dehydrogenase, 11beta-hydroxysteroid dehydrogenase 1, 11beta-hydroxysteroid dehydrogenase 2, 11beta-hydroxysteroid dehydrogenase isoforms 1, 11beta-hydroxysteroid dehydrogenase type 1, 11beta-hydroxysteroid dehydrogenase type 2, 11beta-hydroxysteroid dehydrogenase type I, 11beta-hydroxysteroid dehydrogenase type-1, 11beta-hydroxysteroid dehydrogenase-1, 11beta-hydroxysteroid dehydrogenases type 1, 11beta-hydroxysteroid type 1 dehydrogenase, 11beta-hydroxysteroid-dehydrogenase type I, 11betaHSD1, 11betaHSD2, 11HSD1, beta-hydroxysteroid dehydrogenase, corticosteroid 11-reductase, corticosteroid 11beta-dehydrogenase, dehydrogenase, 11beta-hydroxy steroid, HSD1, HSD11B, HSD11B1, Hsd11B2, HSD2, hydroxysteroid (11-beta) dehydrogenase, isozyme 11beta-HSD1, More, NAD-dependent 11-beta-hydroxysteroid dehydrogenase, NADP(+)-dependent 11beta-dehydrogenase, NADP+-dependent 11beta-hydroxysteroid dehydrogenase 1, type 1 11beta-hydroxysteroid dehydrogenase

ECTree

     1 Oxidoreductases
         1.1 Acting on the CH-OH group of donors
             1.1.1 With NAD+ or NADP+ as acceptor
                1.1.1.146 11beta-hydroxysteroid dehydrogenase

Engineering

Engineering on EC 1.1.1.146 - 11beta-hydroxysteroid dehydrogenase

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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C272S
-
ability to form disulfide bonds abolished, but no change in activity or Km
E25K
-
88% of wild type cortisone reduction activity
E25K/E26K
-
20% of wild type cortisone reduction activity
E25K/E26Q
-
45% of wild type cortisone reduction activity
E25Q
-
82% of wild type cortisone reduction activity
E25Q/E26Q
-
57% of wild type cortisone reduction activity
E26K
-
65% of wild type cortisone reduction activity
K35S/K36S
-
no activity
K5S/K6S
-
93% of wild type cortisone reduction activity, no reduction of 7-oxocholesterol in intact HEK-293 cells transfected with 11beta-HSD1
K5S/K6S/E25K/E26K
-
21% of wild type cortisone reduction activity
K6S/E25K
-
86% of wild type cortisone reduction activity
K6S/E25K/E26K
-
31% of wild type cortisone reduction activity
K6S/E25K/E26Q
-
30% of wild type cortisone reduction activity
K6S/E25Q/E26Q
-
43% of wild type cortisone reduction activity
L150R
-
also lacking the first 30 n-terminal amino acids, gains activity in microsomal fraction after solubilization with Emulgen
V148R
-
also lacking the first 30 N-terminal amino acids, no activity
V149E
V149R
Y177A
-
site-directed mutagenesis, the mutant shows increased Km for cortisone compared to the wild-type enzyme, the mutation reduces the sensitivity to glycyrrhetinic acid inhibition 6-10fold, but not to carbenoxolone
Y177F
-
site-directed mutagenesis, the mutant shows kinetics similar to the wild-type enzyme
Y177Q
-
site-directed mutagenesis, the mutant shows increased Km for cortisone compared to the wild-type enzyme, the mutation reduces the sensitivity to glycyrrhetinic acid inhibition 6-10fold, but not to carbenoxolone
Y280A
wild-type and mutant enzyme exhibit similar Km values for either cortisone or 11-dehydrocorticosterone. About 10fold increase in IC50-value for glycyrrhetinic acid
Y280F
wild-type and mutant enzyme exhibit similar Km values for either cortisone or 11-dehydrocorticosterone. About 6fold increase in IC50-value for glycyrrhetinic acid
Y280S
wild-type and mutant enzyme exhibit similar Km values for either cortisone or 11-dehydrocorticosterone. 100% increase in IC50-value for glycyrrhetinic acid
additional information
a cytoplasmic localized mutant of isozyme 11beta-HSD1 catalyzes the oxoreduction of cortisone, but not of 7-oxocholesterol