Crystallization (Comment) | 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 |
Inhibitors | Comment | 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 | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
DL-glyceraldehyde + NADPH + H+ | Sus scrofa | - |
DL-glycerol + NADP+ | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Sus scrofa | - |
- |
- |
Sus scrofa | P50578 | - |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
kidney | - |
Sus scrofa | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
DL-glyceraldehyde + NADPH + H+ | - |
Sus scrofa | DL-glycerol + NADP+ | - |
? |
Synonyms | Comment | Organism |
---|---|---|
aldehyde reductase | - |
Sus scrofa |
ALR1 | - |
Sus scrofa |
IC50 Value | IC50 Value Maximum | Comment | 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 |