Any feedback?
Please rate this page
(all_enzymes.php)
(0/150)

BRENDA support

1.1.1.21: aldose reductase

This is an abbreviated version!
For detailed information about aldose reductase, go to the full flat file.

Word Map on EC 1.1.1.21

Reaction

alditol
+
NAD(P)+
=
aldose
+
NAD(P)H
+
H+

Synonyms

17betaHSD5, 20-alpha-HSD, 20-alpha-hydroxysteroid dehydrogenase, AdhA, AKR1B, AKR1B1, AKR1B10, AKR1B13, AKR1B14, AKR1B3, AKR1C3, AKR4C7, aldehyde reductase, alditol/NADP+ oxidoreductase, alditol: NADP+ 1-oxidoreductase, alditol:NAD(P)+1oxidoreductase, alditol:NADP 1-oxidoreductase, alditol:NADP oxidoreductase, aldo-keto reductase, aldo-keto reductase family 1 member B1, aldo-keto reductase family 1 member B7, aldoketo reductase 1C3, aldose reductase, aldose reductase 2, aldose reductase-like, aldose reductase-like protein, aldose xylose reductase, ALDRXV4, ALR, ALR1, ALR2, AR, ARI, BAR, EC 1.1.1.139, Fibroblast growth factor regulated protein, FR-1 protein, GRE3, HAR, HRAR, isobutyraldehyde reductase, More, MVDP, NADPH dependent xylose reductase, NADPH-aldopentose reductase, NADPH-aldose reductase, polyol dehydrogenase (NADP2), RLAR, small intestine reductase, TPN-polyol dehydrogenase, VAS deferens androgen-dependent protein, YqhD

ECTree

     1 Oxidoreductases
         1.1 Acting on the CH-OH group of donors
             1.1.1 With NAD+ or NADP+ as acceptor
                1.1.1.21 aldose reductase

Crystallization

Crystallization on EC 1.1.1.21 - aldose reductase

Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
homology modeling of structure, a uniform negative electrostatic potential exists over the protein surface
in complex with citrate and inhibitor fidarestat, resolution of 0.82 A. After the catalytic event, a rearrangement of a bound ligand can trigger the opening of the safety-belt loop of G213-S226, initiating the release of the oxidized cofactor
in complex with inhibitor IDD552, crystallized at pH 5 and 8
in complex with inhibitor zenarestat
in complex with inhibitors tolrestat, 2-(carboxymethyl)-1-oxo-1,2-dihydronaphtho[1,2-d]isothiazole-4-carboxylic acid 3,3-dioxide and 2-[2-(carboxymethoxy)-2-oxoethyl]-1-oxo-1,2-dihydronaphtho[1,2-d]isothiazole-4-carboxylic acid 3,3-dioxide. Unlike tolrestat, the naphthol[1,2-d]isothiazole inhibitors leave the specificity pocket in the closed state and ligand 2-(carboxymethyl)-1-oxo-1,2-dihydronaphtho[1,2-d]isothiazole-4-carboxylic acid 3,3-dioxide extends the catalytic pocket by opening a novel subpocket. Inhibitor 2-[2-(carboxymethoxy)-2-oxoethyl]-1-oxo-1,2-dihydronaphtho[1,2-d]isothiazole-4-carboxylic acid 3,3-dioxide provokes less pronounced induced-fit adaptations of the binding cavity
in complex with NADP+ and inhibitor 4-[3-(3-nitrophenyl)-1,2,4-oxadiazol-5-yl]butanoic acid, 1.43 A resolution. The inhibitor occupies the active site with its carboxylate head group located at the catalytic cavity. In complex with inhibitor {[5-(5-nitrofuran-2-yl)-1,3,4-oxadiazol-2-yl]sulfanyl}acetic acid at 1.55 A resolution. The nitro-aromatic moiety of both inhibitors occupies the specificity pocket of the enzyme, binding to the bottom of the pocket and provoking remarkable induced-fit adaptations
in complex with statil
in complex with the inhibitor IDD 594, hanging drop vapour diffusion method, using 40% (w/v) PEG 6000 in 50 mM diammonium hydrogen citrate at pH 5
molecular docking of glutathione analog gamma-glutamyl-S-(1,2-di-carboxyethyl)-cysteinyl-glycine, into the binding pocket of aldose reductase. Backbone nitrogens of residues Ala299 and Leu300 form a tiny pocket gated by the thiol group of Cys298. The glycine moiety of gamma-glutamyl-S-(1,2-di-carboxyethyl)-cysteinyl-glycine is able to displace the thiol group of Cys298 to make hydrogen bond interactions with the backbone of Ala299, Leu300, and Leu301
-
molecular docking of inhibitor 6-chloro-3-(3,5-dihydroxyphenoxy)-2-oxo-1,8-naphthyridine-1(2H)-carboxylic acid
molecular docking of inhibitor families. Flavonoids tend to bind aldose reductase in E and EC states, while sulfonyl-pyridazinones prefer ES and ECS states. Van der Waals and electrostatic interactions always have positive contributions for stabilizing flavonoids and sulfonyl-pyridazinones. The conserved feature for the aldose reductase binding pocket and the aldose reductase inhibitors is the aromatic stacking and hydrogen bonding
molecular docking of inhibitors
molecular modeling of complex with NADP+ and inhibitor (2Z)-3-(3,4-dihydroxyphenyl)-2-[(4-methylphenyl)carbonyl]prop-2-enoic acid
purified recombinant ALR2, with the oxidized form of beta-NADPH, pH 5.0, 4°C, X-ray diffraction structure determination and analysis at 1.8 A resolution
-
purified recombinant enzyme ALR2 in complex with inhibitor 17744184, hanging drop vapour diffusion method, mixing of 15 mg/mL ALR2 protein solution with reservoir solution containing 5% w/v PEG 6000, 5.15 mg/mL DTT, 0.66 mg/mL NADP+, and 50 mM diammonium hydrogen citrate, pH 5.0, equilibration against 1 mL of well solution containing 20% w/v PEG 6000 in 120 mM diammonium hydrogen citrate, pH 5.0, 3 days at 4°C and 2-4 days at 18°C, X-ray diffraction structure determination and analysis at 1.26 A resolution
purified recombinant enzyme in complex with 6-[(5-chloro-3-methyl-1-benzofuran-2-yl)sulfonyl]pyridazin-3(2H)-one, 20 mg/ml protein in 50 mM diammonium hydrogen citrate, pH 5.0, mixed with NADP+-containing solution in a ratio 1:3, hanging drop vapour diffusion method, soaking in 6-[(5-chloro-3-methyl-1-benzofuran-2-yl)sulfonyl]pyridazin-3(2H)-one solution, containing 5% v/v isopropanol, 5% v/v DMSO, 5% w/v beta-cyclodextrin, 25% w/v PEG 6000, 50 mM diammonium hydrogen citrate pH 5.0, and saturated pyridazinone-type inhibitor, 20°C, 3 days, X-ray diffraction structure determination and analysis at 0.95-1.43 A resolution, modeling
purified recombinant His-tagged ALR2 in complex with inhibitors sulindac, sulindac sulfide, sulindac sulfone, and tolmetin, hanging drop vapor diffusion method, 25 mg/ml enzyme with two equivalents of NADP+ and 7.5% PEG 6000 were equilibrated against a well containing 1 ml of 120 mM ammonium citrate, pH 5.0, 20% m/v PEG 6000, soaking of crystals in inhibitor saturated solution containing 25% m/v PEG 6000, 50 mM ammonium citrate, pH 5.0, and 5% v/v DMSO, X-ray diffraction structure determination and analysis
purified recombinant R268A mutant enzyme, hanging drop vapour diffusion method, 30 mg/ml protein in 5 mM phosphate, pH 7.0, mixing with equal volume of well solution containing 20% v/v PEG 6000, 25 mM MES, pH 6.0, and 16 mM ammonium sulfate, 3 weeks, X-ray diffraction structure determination and analysis at 2.8 A resolution
-
purified recombinant wild-type enzyme and mutant AKR1B10 V301L holoenzyme in complex with inhibitor fidarestat and NADP+, X-ray diffraction structure determination and analysis 1.60 A resolution by replacement soaking of crystals containing inhibitor tolrestat for 14 days in 25 mM fidarestat dissolved in the reservoir solution. For crystallization of the enzyme with tolrestat by hanging-drop vapour diffusion method, 0.001 ml of 18 mg/ml protein solution containing 2 mM tolrestat is mixed with 0.001 ml of reservoir solution containing 100 mM sodium cacodylate, pH 9.0, and 30% v/v PEG, 6000, at 24°C
purified recombinant wild-type enzyme complexed with inhibitors phenylacetic acid, 2-hydroxyphenylacetic acid, 2,6-dichlorophenylacetic acid, hexanoic acid, and lipoic acid, hanging drop vapor diffusion method, 4°C, 23-25 mg/ml protein in 0.10 M sodium phosphate buffer, pH 7.0, mixed with well solution containing 20% w/v PEG 6000 and 50 mM sodium citrate, pH 5.0, microseeding, 1 month, crystal stabilization by 0.1 to 1.0% glutaraldehyde, X-ray diffraction structure determination and analysis at 1.7-2.0 A resolution
-
single-crystal x-ray data, neutron Laue data analysis and quantum mechanical modeling of aldose reductase. Quantum model of catalysis
structural model
-
structures in complex with 2-carbamoyl-phenoxy-acetic acid derivatives. Opening of the protein-binding pocket occurs only once an appropriate substituent is attached to the parent substrate scaffold. Up to five water molecules entering the opened pocket cannot stabilize this state. Sole substitution with a benzyl group stabilizes the opened state, and the energetic barrier for opening is estimated to be about 5 kJ/mol. Additional decoration of the pocket-opening benzyl substituent with a nitro group results in a huge enthalpy-driven potency increase. An isosteric carboxylic acid group reduces the potency 1000fold, and binding occurs without pocket opening
in complex with NADPH, to 2.4 A resolution. Space group P412121 or P43212
docking studies of rhodanine-3-hippuric acid and its benzylidene derivatives
-
hanging drop vapour diffusion method, using 0.1 M HEPES pH 7.5, 20% (w/v) polyethylene glycol 4000 and 10% (v/v) 2-propanol
-
molecular docking predicts the binding sites between aldose reductase and gigantol to be residues Trp111, His110, Tyr48 and Trp20
-
purified recombinant enzyme in ternary/binary complex with inhibitor nitazoxanide and/or NADP+, or with NADP+ and glyceraldehyde, for enzyme-NADP+-nitazoxanide complex, enzyme-NADP+ crystals are soaked in a saturated solution of nitazoxanide containing 50% N,N-dimethylformamide, 50 mM ammonium citrate, pH 5.0, and 12.5% PEG 6000, for enzyme-NADP+-D-glyceraldehyde complex, enzyme-NADP+ crystals are soaked in a solution containing 20% pyridine, 0.3 M D,L-glyceraldehyde, 50 mM ammonium citrate, pH 5.0, and 12.5% m/v PEG 6000, X-ray diffraction structure determination and analysis, modeling
-
purified enzyme in complex with inhibitor fidaresta, X-ray diffraction structure determination and analysis at 1.85 A resolution
-
space group P212121, resolution to 2.0 A