Literature summary for 1.1.1.21 extracted from

Ruiz, F.X.; Cousido-Siah, A.; Mitschler, A.; Farres, J.; Pares, X.; Podjarny, A.
X-ray structure of the V301L aldo-keto reductase 1B10 complexed with NADP+ and the potent aldose reductase inhibitor fidarestat: implications for inhibitor binding and selectivity (2013), Chem. Biol. Interact., 202, 178-185.

Cloned(Commentary)

Cloned (Comment)	Organism
gene AKR1B1, recombinant expression of His-tagged enzyme in Escherichia coli strain BL21(DE3)	Homo sapiens
gene AKR1B10, recombinant expression of His-tagged wild-type and mutant enzymes in Escherichia coli strain BL21(DE3)	Homo sapiens

Crystallization (Commentary)

Crystallization (Comment)	Organism
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	Homo sapiens

Crystallization (Comment)

Organism

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

Homo sapiens

Protein Variants

Protein Variants	Comment	Organism
V301L	site-directed mutagenesis	Homo sapiens

Inhibitors

Inhibitors	Comment	Organism	Structure
fidarestat	an inhibitor highly selective for aldose reductase (AKR1B1, EC 1.1.1.21) versus aldehyde reductase (AKR1A1, EC 1.1.1.2). Inhibitor binding site and structure comparisons of enzymes AKR1B1 and AKR1B10, overview. Fidarestat is specific for aldose reductase AKR1B1 versus aldose reductae-like AKR1B10; an inhibitor highly selective for aldose reductase (AKR1B1, EC 1.1.1.21) versus aldehyde reductase (AKR1A1, EC 1.1.1.2). Inhibitor binding site and structure comparisons of enzymes AKR1B1 and AKR1B10, overview. Fidarestat is specific for aldose reductase AKR1B1 versus aldose reductae-like AKR1B10	Homo sapiens

KM Value [mM]

KM Value [mM]	KM Value Maximum [mM]	Substrate	Comment	Organism	Structure
6	-	DL-glyceraldehyde	pH 7.0, 25°C, recombinant detagged enzyme	Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
D-glucose + NADPH + H+	Homo sapiens	-	sorbitol + NADP+	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	O60218	-	-
Homo sapiens	P15121	-	-

Purification (Commentary)

Purification (Comment)	Organism
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography, tag cleavage by thrombin, followed by anion exchange chromatography	Homo sapiens
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli strain BL21(DE3) by nickel affinity chromatography, tag cleavage by thrombin, followed by anion exchange chromatography	Homo sapiens

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
D-glucose + NADPH + H+	-	Homo sapiens	sorbitol + NADP+	-	?
DL-glyceraldehyde + NADPH + H+	-	Homo sapiens	glycerol + NADP+	-	?

Synonyms

Synonyms	Comment	Organism
AKR1B1	-	Homo sapiens
AKR1B10	-	Homo sapiens
aldose reductase	-	Homo sapiens
aldose reductase-like	-	Homo sapiens
small intestine reductase	-	Homo sapiens

Temperature Optimum [°C]

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

pH Optimum

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

Cofactor

Cofactor	Comment	Organism	Structure
NADPH	-	Homo sapiens

IC50 Value

IC50 Value	IC50 Value Maximum	Comment	Organism	Inhibitor
0.000026	-	pH 7.0, 25°C, recombinant detagged enzyme	Homo sapiens	fidarestat
0.0018	-	pH 7.0, 25°C, recombinant detagged enzyme	Homo sapiens	fidarestat
0.033	-	pH 7.0, 25°C, recombinant detagged wild-type enzyme	Homo sapiens	fidarestat

Expression

Organism	Comment	Expression
Homo sapiens	aldose reductase is upregulated in hyperglycemia	up

General Information

General Information	Comment	Organism
evolution	the enzyme AKR1B1 belongs to the AKR1B subfamily	Homo sapiens
evolution	the enzyme AKR1B10 belongs to the AKR1B subfamily	Homo sapiens
physiological function	AKR1B10 is a tumor marker and displays high activity with the retinoic acid precursor all-trans-retinaldehyde and is induced in different types of cancer, notably in non-small cell lung and hepatocellular carcinomas	Homo sapiens