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Literature summary for 1.3.1.3 extracted from

  • Drury, J.E.; Mindnich, R.; Penning, T.M.
    Characterization of disease-related 5beta-reductase (AKR1D1) mutations reveals their potential to cause bile acid deficiency (2010), J. Biol. Chem., 285, 24529-24537.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
expression in Escherichia coli and HEK-293 cell Homo sapiens
recombinant expression of AKR1D1 enzyme mutants in HEK-293 cells Homo sapiens

Protein Variants

Protein Variants Comment Organism
G223E naturally occuring mutation, identified in patients with functional bile acid deficiency, inactive mutant Homo sapiens
L106F mutant identified in patient with reduced enzymic activity Homo sapiens
L106F naturally occuring mutation, identified in patients with functional bile acid deficiency, almost inactive mutant Homo sapiens
P133R mutant identified in patient with reduced enzymic activity Homo sapiens
P133R mutant identified in patient with reduced enzymic activity. Mutant displays a highly reduced Km and Vmax reminiscent of uncompetitive kinetics with 4-cholesten-7alpha-ol-3-one as substrate. Mutant displays no change in cofactor affinity but is more thermolabile in the absence of NADPH Homo sapiens
P133R naturally occuring mutation, identified in patients with functional bile acid deficiency, AKR1D1-P133R activity is significantly reduced compared with wild-type enzyme Homo sapiens
P198L mutant identified in patient with reduced enzymic activity Homo sapiens
P198L naturally occuring mutation, identified in patients with functional bile acid deficiency, inactive mutant Homo sapiens
R261C mutant identified in patient with reduced enzymic activity Homo sapiens
R261C naturally occuring mutation, identified in patients with functional bile acid deficiency, almost inactive mutant Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
testosterone substrate inhibition; substrate inhibition of the wild-type enzyme Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
additional information Henri-Michaelis-Menten steady-state kinetics of mutant enzyme P133R Homo sapiens
0.0013
-
cortisone mutant P133R, pH not specified in the publication, temperature not specified in the publication Homo sapiens
0.0013
-
cortisone pH 6.0, 37°C, mutant P133R Homo sapiens
0.0027
-
testosterone pH 6.0, 37°C, wild-type enzyme Homo sapiens
0.0027
-
testosterone wild-type, pH not specified in the publication, temperature not specified in the publication Homo sapiens
0.0127
-
testosterone mutant P133R, pH not specified in the publication, temperature not specified in the publication Homo sapiens
0.0127
-
testosterone pH 6.0, 37°C, mutant P133R Homo sapiens
0.0151
-
cortisone pH 6.0, 37°C, wild-type enzyme Homo sapiens
0.0151
-
cortisone wild-type, pH not specified in the publication, temperature not specified in the publication Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
cortisone + NADPH + H+ Homo sapiens
-
17,21-dihydroxy-5beta-pregnane-3,11,20-trione + NADP+
-
?
testosterone + NADPH + H+ Homo sapiens
-
(5beta,17beta)-17-hydroxyandrostan-3-one + NADP+
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-
Homo sapiens P51857
-
-

Purification (Commentary)

Purification (Comment) Organism
recombinant AKR1D1 enzyme mutant P133R from HEK-293 cells, the other expressed mutants cannot be purified Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
cortisone + NADPH + H+
-
Homo sapiens 17,21-dihydroxy-5beta-pregnane-3,11,20-trione + NADP+
-
?
additional information the enzyme catalyzes stereo-specifically reduces the DELTA4 double bond in 3-keto steroids and sterols to yield the 5beta-hydrogenated product Homo sapiens ?
-
?
testosterone + NADPH + H+
-
Homo sapiens (5beta,17beta)-17-hydroxyandrostan-3-one + NADP+
-
?

Subunits

Subunits Comment Organism
More structure-function relationship, overview Homo sapiens

Synonyms

Synonyms Comment Organism
AKR1D1
-
Homo sapiens
aldo-keto reductase 1D1
-
Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
assay at Homo sapiens

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.01
-
cortisone mutant P133R, pH not specified in the publication, temperature not specified in the publication Homo sapiens
0.01
-
cortisone pH 6.0, 37°C, mutant P133R Homo sapiens
0.012
-
testosterone pH 6.0, 37°C, wild-type enzyme Homo sapiens
0.045
-
testosterone pH 6.0, 37°C, mutant P133R Homo sapiens
0.05
-
testosterone mutant P133R, pH not specified in the publication, temperature not specified in the publication Homo sapiens
0.12
-
testosterone wild-type, pH not specified in the publication, temperature not specified in the publication Homo sapiens
0.165
-
cortisone pH 6.0, 37°C, wild-type enzyme Homo sapiens
0.17
-
cortisone wild-type, pH not specified in the publication, temperature not specified in the publication Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
6
-
assay at Homo sapiens

Cofactor

Cofactor Comment Organism Structure
NADPH
-
Homo sapiens

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.0145
-
testosterone wild-type, pH not specified in the publication, temperature not specified in the publication Homo sapiens
0.0145
-
testosterone pH 6.0, 37°C, wild-type enzyme Homo sapiens

General Information

General Information Comment Organism
additional information structure-function relationship, overview Homo sapiens

kcat/KM [mM/s]

kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
3.5
-
testosterone mutant P133R, pH not specified in the publication, temperature not specified in the publication Homo sapiens
3.54
-
testosterone pH 6.0, 37°C, mutant P133R Homo sapiens
4.44
-
testosterone pH 6.0, 37°C, wild-type enzyme Homo sapiens
7.69
-
cortisone pH 6.0, 37°C, mutant P133R Homo sapiens
7.7
-
cortisone mutant P133R, pH not specified in the publication, temperature not specified in the publication Homo sapiens
10.93
-
cortisone pH 6.0, 37°C, wild-type enzyme Homo sapiens
11
-
cortisone wild-type, pH not specified in the publication, temperature not specified in the publication Homo sapiens
43.8
-
testosterone wild-type, pH not specified in the publication, temperature not specified in the publication Homo sapiens