1.3.1.3: DELTA4-3-oxosteroid 5beta-reductase

This is an abbreviated version!
For detailed information about DELTA4-3-oxosteroid 5beta-reductase, go to the full flat file.

Word Map on EC 1.3.1.3

Reaction

17,21-dihydroxy-5beta-pregnane-3,11,20-trione
+
NADP+
=
cortisone
+
NADPH
+
H+

Synonyms

3-oxo-DELTA4-steroid 5beta-reductase, 4,5beta-dihydrocortisone:NADP+ DELTA4-oxidoreductase, 5-beta-reductase, 5beta-POR, 5beta-red, AKR1D1, aldo-keto reductase, aldo-keto reductase 1D1, aldo–keto reductase 1D1, androstenedione 5beta-reductase, cortisone 5beta-reductase, cortisone beta-reductase, DELTA 4-5beta-reductase, DELTA4-3-ketosteroid 5beta-reductase, DELTA4-3-oxosteroid 5beta-reductase, DELTA4-hydrogenase, EC 1.3.1.3, h5beta-red, h5beta-reductase, More, P5betaR, progesterone 5beta-reductase, reductase, cholestenone 5beta.-, reductase, cortisone DELTA4-5beta-, steroid 5beta-reductase, steroid 5beta.-reductase, testosterone 5-beta-reductase, testosterone 5beta-reductase

ECTree

     1 Oxidoreductases
         1.3 Acting on the CH-CH group of donors
             1.3.1 With NAD+ or NADP+ as acceptor
                1.3.1.3 DELTA4-3-oxosteroid 5beta-reductase

Engineering

Engineering on EC 1.3.1.3 - DELTA4-3-oxosteroid 5beta-reductase

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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C352G
-
site-directed mutagenesis, mutation at the substrate binding site, the mutant shows reduced activity compared to the wild-type enzyme
D181T/L182Q
-
site-directed mutagenesis, mutation at motif V, the mutant shows reduced activity compared to the wild-type enzyme
F353M
-
site-directed mutagenesis, mutation at the substrate binding site, the mutant shows similar activity as the wild-type enzyme
F353P
-
site-directed mutagenesis, mutation at the substrate binding site, the mutant shows similar activity as the wild-type enzyme
G204N
-
site-directed mutagenesis, mutation at motif IV, the mutant shows reduced activity compared to the wild-type enzyme
L182Q
-
site-directed mutagenesis, mutation at motif V, the mutant shows similar activity as the wild-type enzyme
M150L
-
site-directed mutagenesis, mutation at motif IV, the mutant shows similar activity as the wild-type enzyme
N205A
-
site-directed mutagenesis, mutation at the substrate binding site, the mutant shows increased activity compared to the wild-type enzyme
N205M
-
site-directed mutagenesis, mutation at the substrate binding site, the mutant shows increased activity compared to the wild-type enzyme
N205M/Y156V
-
site-directed mutagenesis, double mutation at the substrate binding site, the mutant shows increased activity compared to the wild-type enzyme
R146T
-
site-directed mutagenesis, mutation at motif IV, the mutant shows similar activity as the wild-type enzyme
S248M
-
site-directed mutagenesis, mutation near the substrate binding site, inactive mutant
T65P
-
site-directed mutagenesis, mutation at near motif II, the mutant shows similar activity as the wild-type enzyme
Y156V
-
site-directed mutagenesis, mutation at the substrate binding site, the mutant shows increased activity compared to the wild-type enzyme
Y179A
-
inactive
Y179F
-
inactive
Y302F
-
site-directed mutagenesis, mutation at motif IV, the mutant shows similar activity as the wild-type enzyme
E120A
-
mutant is devoid of activity
G223E
L106F
P133R
P198L
R217stop
the naturally occuring mutation of gene SRD5B1 are involved in hyper-3-oxo-DELTA4 bile aciduria from primary 3-oxo-DELTA4-steroid 5beta-reductase deficiency, phenotypes, overview
R261C
V309F
-
replacement of one of the residues delineating this site by a phenylalanine completely abolishes the enzyme's substrate inhibition, but the catalytic efficiency of the mutated enzyme is similar to that of the wild-type h5beta-red enzyme
Y132F
-
replacement of one of the residues delineating this site by a phenylalanine completely abolishes the enzyme's substrate inhibition, but the catalytic efficiency of the mutated enzyme is similar to that of the wild-type h5beta-red enzyme
Y58F
-
mutant is devoid of activity
additional information
-
determination of AKR1D1 reaction mechanism by mutational analysis revealing that the 4-pro-R hydride is transferred from the re-face of the nicotinamide ring to C5 of the steroid substrate. E120, a unique substitution in the AKR catalytic tetrad, permits a deeper penetration of the steroid substrate into the active site to promote optimal reactant positioning. It participates with Y58 to create a superacidic oxyanion hole for polarization of the C3 ketone, no role for K87 in the proton relay, overview