BRENDA - Enzyme Database
show all sequences of 1.1.1.2

Structure of aldehyde reductase in ternary complex with a 5-arylidene-2,4-thiazolidinedione aldose reductase inhibitor

Carbone, V.; Giglio, M.; Chung, R.; Huyton, T.; Adams, J.; Maccari, R.; Ottana, R.; Hara, A.; El-Kabbani, O.; Eur. J. Med. Chem. 45, 1140-1145 (2010)

Data extracted from this reference:

Crystallization (Commentary)
Crystallization (Commentary)
Organism
in ternary complex with NADPH and a 5-arylidene-2,4-thiazolidinedione aldose reductase inhibitor, [5-(3-carboxymethoxy-4-methoxybenzylidene)-2,4-dioxothiazolidin-3-yl]acetic acid to 1.99 A resolution. The partially disordered inhibitor forms a tight network of hydrogen bonds with the active site residues Tyr50 and His113 and coenzyme. pi-Stacking interactions with several conserved active site tryptophan residues and hydrogen-bonding interactions with the non-conserved C-terminal residue Pro301 in aldehyde reductase ALR1 contribute to inhibitor selectivity. In particular for the potent inhibitor [5-(3-carboxymethoxy-4-methoxybenzylidene)-2,4-dioxothiazolidin-3-yl]acetic acid, the rotameric state of the conserved residue Trp220 in ALR1, i.e Trp 219 in aldose reductase, is important in forming a pi-stacking interaction with the inhibitor in aldose reductase and contributes to the difference in the binding of the inhibitor to the enzymes; purified aldehyde reductase, ALR1, in ternary complex with NADPH and [5-(3-carboxymethoxy-4-methoxybenzylidene)-2,4-dioxothiazolidin-3-yl]acetic acid, hanging drop method, 17-18 mg/ml protein in 5 mM Tris-HCl, pH 6.5, containing 5 mM 2-mercaptoethanol, mixed with NADPH and inhibitor in a 1:20:3molar ratio, the reservoir solution contains 2.0 M ammonium sulfate, and 0.1 M Tris-HCl buffer, pH 8.5, 10 days, X-ray diffraction structure determination and analysis at 1.99 A resolution
Sus scrofa
Inhibitors
Inhibitors
Commentary
Organism
Structure
additional information
enzyme active site interactions with the 3-carboxymethoxy-4-methoxy-phenyl moiety of the inhibitor, binding structure, overview
Sus scrofa
[5-(3-carboxymethoxy-4-methoxybenzylidene)-2,4-dioxothiazolidin-3-yl]acetic acid
crystallization data. The rotameric state of the conserved residue Trp220 in aldehyde reductase ALR1, i.e Trp 219 in aldose reductase ALR2, is important in forming a pi-stacking interaction with the inhibitor in aldose reductase and contributes to the difference in the binding of the inhibitor to the enzymes; i.e. CMD, a potent inhibitor of ALR2, but not for ALR1. For binding to ALR1, the partially disordered inhibitor forms a tight network of hydrogen bonds with the active site residues Tyr50 and His113 and NADPH, structure molecular modelling, overview. The non-conserved C-terminal residue Leu300 in ALR2, which is Pro301 in ALR1, contributes to inhibitor selectivity
Sus scrofa
[5-(3-hydroxy-4-methoxybenzylidene)-2,4-dioxothiazolidin-3-yl]acetic acid
; i.e. HMD, modelling of inhibitor-enzyme active site complex
Sus scrofa
Natural Substrates/ Products (Substrates)
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
ID
DL-glyceraldehyde + NADPH + H+
Sus scrofa
-
DL-glycerol + NADP+
-
-
?
Organism
Organism
UniProt
Commentary
Textmining
Sus scrofa
P50578
-
-
Sus scrofa
-
-
-
Source Tissue
Source Tissue
Commentary
Organism
Textmining
kidney
;
Sus scrofa
-
Substrates and Products (Substrate)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
Substrate Product ID
DL-glyceraldehyde + NADPH + H+
-
711903
Sus scrofa
DL-glycerol + NADP+
-
-
-
?
Synonyms
Synonyms
Commentary
Organism
aldehyde reductase
-
Sus scrofa
ALR1
-
Sus scrofa
IC50 Value
IC50 Value
IC50 Value Maximum
Commentary
Organism
Inhibitor
Structure
0.0054
-
25°C, pH 6.7; ALR1, pH not specified in the publication, temperature not specified in the publication
Sus scrofa
[5-(3-carboxymethoxy-4-methoxybenzylidene)-2,4-dioxothiazolidin-3-yl]acetic acid
0.037
-
25°C, pH 6.7; ALR1, pH not specified in the publication, temperature not specified in the publication
Sus scrofa
[5-(3-hydroxy-4-methoxybenzylidene)-2,4-dioxothiazolidin-3-yl]acetic acid
Crystallization (Commentary) (protein specific)
Crystallization
Organism
in ternary complex with NADPH and a 5-arylidene-2,4-thiazolidinedione aldose reductase inhibitor, [5-(3-carboxymethoxy-4-methoxybenzylidene)-2,4-dioxothiazolidin-3-yl]acetic acid to 1.99 A resolution. The partially disordered inhibitor forms a tight network of hydrogen bonds with the active site residues Tyr50 and His113 and coenzyme. pi-Stacking interactions with several conserved active site tryptophan residues and hydrogen-bonding interactions with the non-conserved C-terminal residue Pro301 in aldehyde reductase ALR1 contribute to inhibitor selectivity. In particular for the potent inhibitor [5-(3-carboxymethoxy-4-methoxybenzylidene)-2,4-dioxothiazolidin-3-yl]acetic acid, the rotameric state of the conserved residue Trp220 in ALR1, i.e Trp 219 in aldose reductase, is important in forming a pi-stacking interaction with the inhibitor in aldose reductase and contributes to the difference in the binding of the inhibitor to the enzymes
Sus scrofa
purified aldehyde reductase, ALR1, in ternary complex with NADPH and [5-(3-carboxymethoxy-4-methoxybenzylidene)-2,4-dioxothiazolidin-3-yl]acetic acid, hanging drop method, 17-18 mg/ml protein in 5 mM Tris-HCl, pH 6.5, containing 5 mM 2-mercaptoethanol, mixed with NADPH and inhibitor in a 1:20:3molar ratio, the reservoir solution contains 2.0 M ammonium sulfate, and 0.1 M Tris-HCl buffer, pH 8.5, 10 days, X-ray diffraction structure determination and analysis at 1.99 A resolution
Sus scrofa
IC50 Value (protein specific)
IC50 Value
IC50 Value Maximum
Commentary
Organism
Inhibitor
Structure
0.0054
-
25°C, pH 6.7
Sus scrofa
[5-(3-carboxymethoxy-4-methoxybenzylidene)-2,4-dioxothiazolidin-3-yl]acetic acid
0.0054
-
ALR1, pH not specified in the publication, temperature not specified in the publication
Sus scrofa
[5-(3-carboxymethoxy-4-methoxybenzylidene)-2,4-dioxothiazolidin-3-yl]acetic acid
0.037
-
25°C, pH 6.7
Sus scrofa
[5-(3-hydroxy-4-methoxybenzylidene)-2,4-dioxothiazolidin-3-yl]acetic acid
0.037
-
ALR1, pH not specified in the publication, temperature not specified in the publication
Sus scrofa
[5-(3-hydroxy-4-methoxybenzylidene)-2,4-dioxothiazolidin-3-yl]acetic acid
Inhibitors (protein specific)
Inhibitors
Commentary
Organism
Structure
additional information
enzyme active site interactions with the 3-carboxymethoxy-4-methoxy-phenyl moiety of the inhibitor, binding structure, overview
Sus scrofa
[5-(3-carboxymethoxy-4-methoxybenzylidene)-2,4-dioxothiazolidin-3-yl]acetic acid
crystallization data. The rotameric state of the conserved residue Trp220 in aldehyde reductase ALR1, i.e Trp 219 in aldose reductase ALR2, is important in forming a pi-stacking interaction with the inhibitor in aldose reductase and contributes to the difference in the binding of the inhibitor to the enzymes
Sus scrofa
[5-(3-carboxymethoxy-4-methoxybenzylidene)-2,4-dioxothiazolidin-3-yl]acetic acid
i.e. CMD, a potent inhibitor of ALR2, but not for ALR1. For binding to ALR1, the partially disordered inhibitor forms a tight network of hydrogen bonds with the active site residues Tyr50 and His113 and NADPH, structure molecular modelling, overview. The non-conserved C-terminal residue Leu300 in ALR2, which is Pro301 in ALR1, contributes to inhibitor selectivity
Sus scrofa
[5-(3-hydroxy-4-methoxybenzylidene)-2,4-dioxothiazolidin-3-yl]acetic acid
-
Sus scrofa
[5-(3-hydroxy-4-methoxybenzylidene)-2,4-dioxothiazolidin-3-yl]acetic acid
i.e. HMD, modelling of inhibitor-enzyme active site complex
Sus scrofa
Natural Substrates/ Products (Substrates) (protein specific)
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
ID
DL-glyceraldehyde + NADPH + H+
Sus scrofa
-
DL-glycerol + NADP+
-
-
?
Source Tissue (protein specific)
Source Tissue
Commentary
Organism
Textmining
kidney
-
Sus scrofa
-
Substrates and Products (Substrate) (protein specific)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
ID
DL-glyceraldehyde + NADPH + H+
-
711903
Sus scrofa
DL-glycerol + NADP+
-
-
-
?
Other publictions for EC 1.1.1.2
No.
1st author
Pub Med
title
organims
journal
volume
pages
year
Activating Compound
Application
Cloned(Commentary)
Crystallization (Commentary)
Engineering
General Stability
Inhibitors
KM Value [mM]
Localization
Metals/Ions
Molecular Weight [Da]
Natural Substrates/ Products (Substrates)
Organic Solvent Stability
Organism
Oxidation Stability
Posttranslational Modification
Purification (Commentary)
Reaction
Renatured (Commentary)
Source Tissue
Specific Activity [micromol/min/mg]
Storage Stability
Substrates and Products (Substrate)
Subunits
Synonyms
Temperature Optimum [°C]
Temperature Range [°C]
Temperature Stability [°C]
Turnover Number [1/s]
pH Optimum
pH Range
pH Stability
Cofactor
Ki Value [mM]
pI Value
IC50 Value
Activating Compound (protein specific)
Application (protein specific)
Cloned(Commentary) (protein specific)
Cofactor (protein specific)
Crystallization (Commentary) (protein specific)
Engineering (protein specific)
General Stability (protein specific)
IC50 Value (protein specific)
Inhibitors (protein specific)
Ki Value [mM] (protein specific)
KM Value [mM] (protein specific)
Localization (protein specific)
Metals/Ions (protein specific)
Molecular Weight [Da] (protein specific)
Natural Substrates/ Products (Substrates) (protein specific)
Organic Solvent Stability (protein specific)
Oxidation Stability (protein specific)
Posttranslational Modification (protein specific)
Purification (Commentary) (protein specific)
Renatured (Commentary) (protein specific)
Source Tissue (protein specific)
Specific Activity [micromol/min/mg] (protein specific)
Storage Stability (protein specific)
Substrates and Products (Substrate) (protein specific)
Subunits (protein specific)
Temperature Optimum [°C] (protein specific)
Temperature Range [°C] (protein specific)
Temperature Stability [°C] (protein specific)
Turnover Number [1/s] (protein specific)
pH Optimum (protein specific)
pH Range (protein specific)
pH Stability (protein specific)
pI Value (protein specific)
Expression
General Information
General Information (protein specific)
Expression (protein specific)
KCat/KM [mM/s]
KCat/KM [mM/s] (protein specific)