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1.1.1.357: 3alpha-hydroxysteroid 3-dehydrogenase

This is an abbreviated version!
For detailed information about 3alpha-hydroxysteroid 3-dehydrogenase, go to the full flat file.

Word Map on EC 1.1.1.357

Reaction

a 3alpha-hydroxysteroid
+
NAD(P)+
=
a 3-oxosteroid
+
NAD(P)H
+
H+

Synonyms

17beta-HSD5, 3-alpha hydroxysteroid dehydrogenase type 3, 3-alpha-HSD type 2, 3-alpha-HSD1, 3-alpha-hydroxysteroid dehydrogenase type 2, 3-alpha-hydroxysteroid dehydrogenase type I, 3alpha-HSD, 3alpha-HSD type III, 3alpha-HSD/CR, 3alpha-HSD3, 3alpha-HSOR, 3alpha-hydroxysteroid dehydrogenase, 3alpha-hydroxysteroid dehydrogenase type 3, 3alpha-hydroxysteroid dehydrogenase type III, 3alpha-hydroxysteroid dehydrogenase/carbonyl reductase, 3alpha-hydroxysteroid oxidoreductase, AKR1C1, AKR1C14, AKR1C2, AKR1C3, AKR1C33, AKR1C4, AKR1C9, aldo-keto reductase family 1 member C1, aldo-keto reductase family 1 member C2, aldo-keto reductase family 1 member C3, bile acid binding protein, chlordecone reductase, DD2, DD4, dihydrodiol dehydrogenase, dihydrodiol dehydrogenase 4, dihydrodiol/3alpha-hydroxysteroid dehydrogenase, HSD 28, HSD 29, hsdA, More, NADPH-dependent AKR1C9, Naloxone reductase 2, Ps3alphaHSD, type 1 3alpha-HSD, type 3 3alpha-hydroxysteroid dehydrogenase, type 5 17beta-hydroxysteroid dehydrogenase, type I 3alpha-HSD, type III 3-alpha-hydroxysteroid dehydrogenase

ECTree

     1 Oxidoreductases
         1.1 Acting on the CH-OH group of donors
             1.1.1 With NAD+ or NADP+ as acceptor
                1.1.1.357 3alpha-hydroxysteroid 3-dehydrogenase

Engineering

Engineering on EC 1.1.1.357 - 3alpha-hydroxysteroid 3-dehydrogenase

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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
P185A
site-directed mutagenesis, analysis of kinetics and structure compared to the wild-type enzyme
P185G
site-directed mutagenesis, analysis of kinetics and structure compared to the wild-type enzyme
T188A
site-directed mutagenesis, analysis of kinetics and structure compared to the wild-type enzyme
T188S
site-directed mutagenesis, analysis of kinetics and structure compared to the wild-type enzyme
W173F/P185W
site-directed mutagenesis, analysis of kinetics and structure compared to the wild-type enzyme
W173F/T188W
site-directed mutagenesis, analysis of kinetics and structure compared to the wild-type enzyme
H216F
-
the mutation decreases 3fold the Km for NADP+. The kinetic constants for bile acids with a 12alpha-hydroxy group are decreased 1.5-7fold and those for the other substrates are increased 1.3-9fold. The mutation decreases the stimulatory effects of the enzyme activity by sulfobromophthalein, clofibric acid and thyroxine, which increases the Km for the coenzyme and substrate of the mutant enzymes more highly than those of the wild type enzyme
H216L
-
inactive
H216W
-
inactive
H216Y
-
the mutation decreases 3fold the Km for NADP+. The kinetic constants for bile acids with a 12alpha-hydroxy group are decreased 1.5-7fold and those for the other substrates are increased 1.3-9fold. The mutation decreases the stimulatory effects of the enzyme activity by sulfobromophthalein, clofibric acid and thyroxine, which increases the Km for the coenzyme and substrate of the mutant enzymes more highly than those of the wild type enzyme
V54L
site-directed mutagenesis, the change renders the sequence identical to that of human 20-alpha hydroxysteroid dehydrogenase. The V54L mutation directly restricts the steroid binding modes to a unique one, which resembles the orientation of 20alpha-OHProg within human 20alpha-HSD. The kinetic study shows that the V54L mutation significantly decreases the 3alpha-HSD activity for the reduction of 5alpha-dihydrotestosterone, while this mutation enhances the 20alpha-HSD activity to convert progesterone
F217S
mutation converts AKR1C33 into a dually coenzyme-specific form and abolishes the activity towards 3-keto-5beta-cholestanes that are substrates specific to AKR1C33, and markedly decreases the sensitivity to 4-pregnenes
N272T
mutation does not influence cofactor specificity
K157A
-
site-directed mutagenesis of a catalytic site residue, the NADH binding affinity of K157A mutant is much lower than that of the wild-type resulting in a decreased kcat
S114A
-
site-directed mutagenesis of a catalytic site residue, the mutant shows higher Km and lower kcat values in both oxidation and reduction reactions compared to wild-type
S114A/Y153A
-
site-directed mutagenesis of a catalytic site residue, the double mutant shows higher Km and a highly reduced kcat values in both oxidation and reduction reactions compared to wild-type
Y153A
-
site-directed mutagenesis of a catalytic site residue, the mutant shows higher Km and lower kcat values in both oxidation and reduction reactions compared to wild-type
additional information
when a specific siRNA is used to suppress 3alpha-HSD3 expression without interfering with 3alpha-HSD4, which shares a highly homologous active site, the 5alpha-DHT concentration increases, whereas MCF-7 cell growth is suppressed. Downregulation of 3alpha-HSD3 decreases MCF-7 breast cancer cell growth