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Literature summary extracted from

  • Endo, S.; Matsunaga, T.; Kumada, S.; Fujimoto, A.; Ohno, S.; El-Kabbani, O.; Hu, D.; Toyooka, N.; Mano, J.; Tajima, K.; Hara, A.
    Characterization of rabbit aldose reductase-like protein with 3beta-hydroxysteroid dehydrogenase activity (2012), Arch. Biochem. Biophys., 527, 23-30.
    View publication on PubMed

Cloned(Commentary)

EC Number Cloned (Comment) Organism
1.1.1.270 DNA and amino acid sequence determination and analysis, expression of His-tagged wild-type and mutant enzymes in Escherichia coli strain BL21 (DE3) pLysS Oryctolagus cuniculus

Protein Variants

EC Number Protein Variants Comment Organism
1.1.1.270 F303Q site-directed mutagenesis, the enzyme shows reduced 3-ketoreductase activity compared to the wild-type enzyme Oryctolagus cuniculus
1.1.1.270 F303Q/M304S site-directed mutagenesis, the enzyme shows reduced 3-ketoreductase activity compared to the wild-type enzyme. The double mutation impairs the affinity and catalytic efficiency, although it did not affect the stereospecific reduction of the two 3-ketosteroids into the corresponding 3beta-hydroxysteroids Oryctolagus cuniculus
1.1.1.270 L116F site-directed mutagenesis Oryctolagus cuniculus
1.1.1.270 M304S site-directed mutagenesis, the enzyme shows reduced 3-ketoreductase activity compared to the wild-type enzyme. The M304S mutation causes a 4fold increase in the Km value for pyridine-3-aldehyde Oryctolagus cuniculus

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.1.1.270 (Z)-2-(4-methoxyphenylimino)-7-hydroxy-N-(pyridin-2-yl)-2H-chromene-3-carboxamide noncompetitive in the reduction reaction, competitive in the oxidation reaction Oryctolagus cuniculus
1.1.1.270 3-(4-hydroxy-2-methoxyphenyl)acrylic acid 3-(3-hydroxyphenyl)propyl ester uncompetitive in the reduction reaction, competitive in the oxidation reaction Oryctolagus cuniculus
1.1.1.270 AL1567
-
 Oryctolagus cuniculus
1.1.1.270 bisdemethoxycurcumin
-
 Oryctolagus cuniculus
1.1.1.270 diethylstilbestrol
-
 Oryctolagus cuniculus
1.1.1.270 Diphenic acid competitive in the oxidation reaction Oryctolagus cuniculus
1.1.1.270 epalrestat
-
 Oryctolagus cuniculus
1.1.1.270 minalrestat competitive in the oxidation reaction Oryctolagus cuniculus
1.1.1.270 oleanolic acid competitive in the oxidation reaction Oryctolagus cuniculus
1.1.1.270 quercetin
-
 Oryctolagus cuniculus
1.1.1.270 sorbinil
-
 Oryctolagus cuniculus
1.1.1.270 sulindac
-
 Oryctolagus cuniculus
1.1.1.270 Tolrestat competitive in the oxidation reaction Oryctolagus cuniculus
1.1.1.270 zopolrestat
-
 Oryctolagus cuniculus

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
1.1.1.270 0.001
-
 NADPH pH 7.4, 25°C, wild-type enzyme Oryctolagus cuniculus
1.1.1.270 0.0023
-
 5beta-pregnane-21-ol-3,20-dione pH 7.4, 25°C, mutant L116F Oryctolagus cuniculus
1.1.1.270 0.0024
-
 5beta-pregnane-21-ol-3,20-dione pH 7.4, 25°C, wild-type enzyme Oryctolagus cuniculus
1.1.1.270 0.0035
-
 5beta-dihydrotestosterone pH 7.4, 25°C, wild-type enzyme Oryctolagus cuniculus
1.1.1.270 0.0072
-
 5beta-dihydrotestosterone pH 7.4, 25°C, mutant L116F Oryctolagus cuniculus
1.1.1.270 0.011
-
 Pyridine-3-aldehyde pH 7.4, 25°C, wild-type enzyme and mutant F303Q Oryctolagus cuniculus
1.1.1.270 0.013
-
 5beta-pregnane-21-ol-3,20-dione pH 7.4, 25°C, mutant F303Q Oryctolagus cuniculus
1.1.1.270 0.017
-
 5beta-dihydrotestosterone pH 7.4, 25°C, mutant F303Q Oryctolagus cuniculus
1.1.1.270 0.02
-
 5beta-dihydrotestosterone pH 7.4, 25°C, mutant M304S Oryctolagus cuniculus
1.1.1.270 0.022
-
 Pyridine-3-aldehyde pH 7.4, 25°C, mutant L116F Oryctolagus cuniculus
1.1.1.270 0.023
-
 5beta-pregnane-21-ol-3,20-dione pH 7.4, 25°C, mutant M304S Oryctolagus cuniculus
1.1.1.270 0.039
-
 5beta-dihydrotestosterone pH 7.4, 25°C, mutant F303Q/M304S Oryctolagus cuniculus
1.1.1.270 0.039
-
 Pyridine-3-aldehyde pH 7.4, 25°C, mutant M304S Oryctolagus cuniculus
1.1.1.270 0.048
-
 Pyridine-3-aldehyde pH 7.4, 25°C, mutant F303Q/M304S Oryctolagus cuniculus
1.1.1.270 0.05
-
 5beta-pregnane-21-ol-3,20-dione pH 7.4, 25°C, mutant F303Q/M304S Oryctolagus cuniculus
1.1.1.270 0.18
-
 methylglyoxal pH 7.4, 25°C, mutant L116F Oryctolagus cuniculus
1.1.1.270 0.209
-
 methylglyoxal pH 7.4, 25°C, mutant M304S Oryctolagus cuniculus
1.1.1.270 0.222
-
 methylglyoxal pH 7.4, 25°C, wild-type enzyme Oryctolagus cuniculus
1.1.1.270 0.25
-
 methylglyoxal pH 7.4, 25°C, mutant F303Q/M304S Oryctolagus cuniculus
1.1.1.270 0.253
-
 methylglyoxal pH 7.4, 25°C, mutant F303Q Oryctolagus cuniculus

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
1.1.1.270 cytosol
-
 Oryctolagus cuniculus 5829
-

Molecular Weight [Da]

EC Number Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
1.1.1.270 35000
-
 native enzyme, gel filtration Oryctolagus cuniculus

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.1.1.270 additional information Oryctolagus cuniculus the enzyme, termed AKR1B19, acts not only as a reductase for reactive carbonyl compounds derived from lipid peroxidation like AR-like proteins of other species, but also as a superior reductive 3beta-HSD for 3-keto-5alpha/beta-dihydro-C19/C21/C24-steroids ?
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
1.1.1.270 Oryctolagus cuniculus
-
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
1.1.1.270 native enzyme from lungs by ammonium sufate fractionation, gel filtration, and anion exchange chromatography, recombinant His-tagged wild-type and mutant enzymes from Escherichia coli strain BL21 (DE3) pLysS by nickel affinity chromatography and ultrafiltration Oryctolagus cuniculus

Source Tissue

EC Number Source Tissue Comment Organism Textmining
1.1.1.270 adrenal gland
-
 Oryctolagus cuniculus
-
1.1.1.270 colon
-
 Oryctolagus cuniculus
-
1.1.1.270 lung
-
 Oryctolagus cuniculus
-
1.1.1.270 additional information the enzyme expression occurs in all rabbit tissues, although its expression levels in the renal cortex, adrenal gland, small intestine and colon are high Oryctolagus cuniculus
-
1.1.1.270 renal cortex
-
 Oryctolagus cuniculus
-
1.1.1.270 small intestine
-
 Oryctolagus cuniculus
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.1.1.270 5alpha-androstan-3,17-dione + NADPH + H+
-
 Oryctolagus cuniculus 5alpha-androstan-3beta-ol-17-one + NADP+
-
 r
1.1.1.270 5alpha-dihydrotestosterone + NADPH + H+
-
 Oryctolagus cuniculus 3beta,17beta-dihydroxy-5alpha-androstane + NADP+
-
 r
1.1.1.270 5alpha-pregnan-3,20-dione + NADPH + H+
-
 Oryctolagus cuniculus 5alpha-pregnane-3beta-ol-20-one + NADP+
-
 r
1.1.1.270 5alpha-pregnane-21-ol-3,20-dione + NADPH + H+
-
 Oryctolagus cuniculus 5alpha-pregnane-3beta,21-diol-20-one + NADP+
-
 r
1.1.1.270 5beta-androstan-3,17-dione + NADPH + H+
-
 Oryctolagus cuniculus 5beta-androstan-3beta-ol-17-one + NADP+
-
 r
1.1.1.270 5beta-androstan-3beta-ol-17-one + NADP+
-
 Oryctolagus cuniculus 5beta-androstan-3,17-dione + NADPH + H+
-
 r
1.1.1.270 5beta-androstane-3beta,17beta-diol + NADP+
-
 Oryctolagus cuniculus 5beta-androstane-17beta-ol-3-one + NADPH + H+
-
 r
1.1.1.270 5beta-cholanic acid-3,7-dione + NADPH + H+
-
 Oryctolagus cuniculus 5beta-cholanic acid-3beta-ol-7-one + NADP+
-
 r
1.1.1.270 5beta-dihydrocorticosterone + NADPH + H+
-
 Oryctolagus cuniculus (3beta,5beta,11beta)-3,11,21-trihydroxypregnan-20-one + NADP+
-
 r
1.1.1.270 5beta-dihydrocortisone + NADPH + H+
-
 Oryctolagus cuniculus ?
-
 r
1.1.1.270 5beta-dihydrotestosterone + NADPH + H+
-
 Oryctolagus cuniculus 3beta,17beta-dihydroxy-5beta-androstane + NADP+
-
 r
1.1.1.270 5beta-hydroxy-5beta cholanic acid + NADP+
-
 Oryctolagus cuniculus 3-oxo-5-beta-cholanic acid + NADPH + H+
-
 r
1.1.1.270 5beta-pregnan-3,20-dione + NADPH + H+
-
 Oryctolagus cuniculus 5beta-pregnane-3beta-ol-20-one + NADP+
-
 r
1.1.1.270 5beta-pregnane-20-ol-3-one + NADPH + H+
-
 Oryctolagus cuniculus 5beta-pregnane-3beta,20-diol + NADP+
-
 r
1.1.1.270 5beta-pregnane-21-ol-3,20-dione + NADPH + H+
-
 Oryctolagus cuniculus 5beta-pregnane-3beta,21-diol-20-one + NADP+
-
 r
1.1.1.270 5beta-pregnane-3beta,20alpha-diol + NADP+
-
 Oryctolagus cuniculus 5beta-pregnane-20alpha-ol-3-one + NADPH + H+
-
 r
1.1.1.270 5beta-pregnane-3beta,20beta-diol + NADP+
-
 Oryctolagus cuniculus 5beta-pregnane-20beta-ol-3-one + NADPH + H+
-
 r
1.1.1.270 5beta-pregnane-3beta,21-diol-20-one + NADP+
-
 Oryctolagus cuniculus 5beta-pregnane-21-ol-3,20-dione + NADPH + H+
-
 r
1.1.1.270 5beta-pregnane-3beta-ol-20-one + NADP+
-
 Oryctolagus cuniculus 5beta-pregnan-3,20-dione + NADPH + H+
-
 r
1.1.1.270 dehydrolithocholic acid + NADPH + H+
-
 Oryctolagus cuniculus ?
-
 r
1.1.1.270 farnesol + NADP+
-
 Oryctolagus cuniculus farnesal + NADPH + H+
-
 ?
1.1.1.270 geranylgeraniol + NADP+
-
 Oryctolagus cuniculus geranylgeranial + NADPH + H+
-
 ?
1.1.1.270 isolithocholic acid + NADP+
-
 Oryctolagus cuniculus ? + NADPH + H+
-
 r
1.1.1.270 methylglyoxal + NADP+
-
 Oryctolagus cuniculus ? + NADPH + H+
-
 ?
1.1.1.270 additional information the enzyme, termed AKR1B19, acts not only as a reductase for reactive carbonyl compounds derived from lipid peroxidation like AR-like proteins of other species, but also as a superior reductive 3beta-HSD for 3-keto-5alpha/beta-dihydro-C19/C21/C24-steroids Oryctolagus cuniculus ?
-
 ?
1.1.1.270 additional information substrate specificity of the bifunctional enzyme, for carbonyl compounds and steroids, overview. No reductase activity is observed for 17- and 20-ketosteroids, DELTA4-3-ketosteroids (testosterone, 4-androstene-3,17-dione and progesterone), and prostaglandins (D2, E2, and A1). In the reverse reaction, the enzyme oxidizes 3beta-hydroxy-5alpha/beta-dihydrosteroids, but shows no significant dehydrogenase activity for DELTA5-3beta-hydroxysteroids (dehydroepiandrosterone, pregnenolone, and 5-pregnene-3beta,20alpha-diol) and 3alpha-hydroxysteroids (5alpha/beta-androstan-3alpha-ol-17-ones, 5alpha/beta-androstane-3alpha,17beta-diols, 5alpha/beta-pregnan-3alpha-ol-20-ones and lithocholic acid). The reactivity towards all-trans-retinal of AKR1B19 is low Oryctolagus cuniculus ?
-
 ?
1.1.1.270 pyridine-3-aldehyde + NADP+
-
 Oryctolagus cuniculus pyridin-3-ylmethanol + NADPH + H+
-
 ?

Synonyms

EC Number Synonyms Comment Organism
1.1.1.270 reductive 3beta-HSD
-
 Oryctolagus cuniculus

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
1.1.1.270 25
-
 assay at Oryctolagus cuniculus

Turnover Number [1/s]

EC Number Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
1.1.1.270 0.02
-
 5beta-dihydrotestosterone pH 7.4, 25°C, mutant F303Q/M304S Oryctolagus cuniculus
1.1.1.270 0.023
-
 5beta-pregnane-21-ol-3,20-dione pH 7.4, 25°C, mutant F303Q/M304S Oryctolagus cuniculus
1.1.1.270 0.042
-
 5beta-pregnane-21-ol-3,20-dione pH 7.4, 25°C, mutant M304S Oryctolagus cuniculus
1.1.1.270 0.047
-
 5beta-dihydrotestosterone pH 7.4, 25°C, mutant M304S Oryctolagus cuniculus
1.1.1.270 0.062
-
 5beta-pregnane-21-ol-3,20-dione pH 7.4, 25°C, mutant F303Q Oryctolagus cuniculus
1.1.1.270 0.063
-
 5beta-pregnane-21-ol-3,20-dione pH 7.4, 25°C, mutant L116F Oryctolagus cuniculus
1.1.1.270 0.08
-
 5beta-dihydrotestosterone pH 7.4, 25°C, mutant F303Q Oryctolagus cuniculus
1.1.1.270 0.092
-
 5beta-pregnane-21-ol-3,20-dione pH 7.4, 25°C, wild-type enzyme Oryctolagus cuniculus
1.1.1.270 0.107
-
 5beta-dihydrotestosterone pH 7.4, 25°C, mutant L116F Oryctolagus cuniculus
1.1.1.270 0.113
-
 5beta-dihydrotestosterone pH 7.4, 25°C, wild-type enzyme Oryctolagus cuniculus
1.1.1.270 0.3
-
 methylglyoxal pH 7.4, 25°C, wild-type enzyme Oryctolagus cuniculus
1.1.1.270 0.32
-
 methylglyoxal pH 7.4, 25°C, mutant L116F Oryctolagus cuniculus
1.1.1.270 0.37
-
 methylglyoxal pH 7.4, 25°C, mutant M304S Oryctolagus cuniculus
1.1.1.270 0.4
-
 methylglyoxal pH 7.4, 25°C, mutant F303Q/M304S Oryctolagus cuniculus
1.1.1.270 0.58
-
 methylglyoxal pH 7.4, 25°C, mutant F303Q Oryctolagus cuniculus
1.1.1.270 0.6
-
 Pyridine-3-aldehyde pH 7.4, 25°C, mutant L116F Oryctolagus cuniculus
1.1.1.270 0.72
-
 Pyridine-3-aldehyde pH 7.4, 25°C, wild-type enzyme Oryctolagus cuniculus
1.1.1.270 0.73
-
 NADPH pH 7.4, 25°C, wild-type enzyme Oryctolagus cuniculus
1.1.1.270 0.78
-
 Pyridine-3-aldehyde pH 7.4, 25°C, mutant M304S Oryctolagus cuniculus
1.1.1.270 0.87
-
 Pyridine-3-aldehyde pH 7.4, 25°C, mutant F303Q Oryctolagus cuniculus
1.1.1.270 1.2
-
 Pyridine-3-aldehyde pH 7.4, 25°C, mutant F303Q/M304S Oryctolagus cuniculus

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
1.1.1.270 6.2 6.4
-
 Oryctolagus cuniculus

Cofactor

EC Number Cofactor Comment Organism Structure
1.1.1.270 NADH the NADH-linked reductase activity is only 18% of the NADPH-linked activity Oryctolagus cuniculus
1.1.1.270 NADPH AKR1B19 shows high coenzyme preference to NADPH Oryctolagus cuniculus

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
1.1.1.270 0.000008
-
 pH 7.4, 25°C, wild-type enzyme Oryctolagus cuniculus (Z)-2-(4-methoxyphenylimino)-7-hydroxy-N-(pyridin-2-yl)-2H-chromene-3-carboxamide
1.1.1.270 0.000043
-
 pH 7.4, 25°C, wild-type enzyme Oryctolagus cuniculus minalrestat
1.1.1.270 0.00006
-
 pH 7.4, 25°C, wild-type enzyme Oryctolagus cuniculus 3-(4-hydroxy-2-methoxyphenyl)acrylic acid 3-(3-hydroxyphenyl)propyl ester
1.1.1.270 0.00016
-
 pH 7.4, 25°C, wild-type enzyme Oryctolagus cuniculus Tolrestat
1.1.1.270 0.0004
-
 pH 7.4, 25°C, wild-type enzyme Oryctolagus cuniculus oleanolic acid
1.1.1.270 0.0006
-
 pH 7.4, 25°C, wild-type enzyme Oryctolagus cuniculus bisdemethoxycurcumin
1.1.1.270 0.00086
-
 pH 7.4, 25°C, wild-type enzyme Oryctolagus cuniculus sulindac
1.1.1.270 0.0012
-
 pH 7.4, 25°C, wild-type enzyme Oryctolagus cuniculus zopolrestat
1.1.1.270 0.0015
-
 pH 7.4, 25°C, wild-type enzyme Oryctolagus cuniculus quercetin
1.1.1.270 0.0015
-
 pH 7.4, 25°C, wild-type enzyme Oryctolagus cuniculus epalrestat
1.1.1.270 0.0017
-
 pH 7.4, 25°C, wild-type enzyme Oryctolagus cuniculus AL1567
1.1.1.270 0.0028
-
 pH 7.4, 25°C, wild-type enzyme Oryctolagus cuniculus diethylstilbestrol
1.1.1.270 0.0053
-
 pH 7.4, 25°C, wild-type enzyme Oryctolagus cuniculus sorbinil
1.1.1.270 0.26
-
 pH 7.4, 25°C, wild-type enzyme Oryctolagus cuniculus Diphenic acid

General Information

EC Number General Information Comment Organism
1.1.1.270 evolution the rabbit aldose reductase-like protein that shars an 86% sequence identity to human aldo-keto reductase (AKR) 1B10 and is assigned as AKR1B19 in the AKR superfamily. It is bifunctional and also acts as a 3-ketoreductase reducing 3-keto-5alpha/beta-dihydro-C19/C21/C24-steroids into the corresponding 3betahydroxysteroids Oryctolagus cuniculus
1.1.1.270 malfunction single and double mutations, F303Q, M304S and F303Q/M304S, significantly impair the 3-ketoreductase activity, suggesting that the two residues play critical roles in recognition of the steroidal substrate Oryctolagus cuniculus
1.1.1.270 physiological function the rabbit aldose reductase-like protein, assigned as AKR1B19, is bifunctional, it shows aldose reductase activity for various aldehydes and alpha-dicarbonyl compounds acting as a defense system against cytotoxic carbonyl compounds in rabbit tissues, and it also acts as a 3-ketoreductase reducing 3-keto-5alpha/beta-dihydro-C19/C21/C24-steroids into the corresponding 3beta-hydroxysteroids Oryctolagus cuniculus