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

BRENDA support

Literature summary extracted from

  • El-Kabbani, O.; Carbone, V.; Darmanin, C.; Oka, M.; Mitschler, A.; Podjarny, A.; Schulze-Briese, C.; Chung, R.P.
    Structure of aldehyde reductase holoenzyme in complex with the potent aldose reductase inhibitor fidarestat: implications for inhibitor binding and selectivity (2005), J. Med. Chem., 48, 5536-5542.
    View publication on PubMed

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
1.1.1.2 hanging drop method, with NADPH, ammonium sulfate, Tris HCl-buffer, pH 8.1, buffer C, maximum side: 0.3 mm x 0.1 mm x 0,1 mm after 1 week Sus scrofa
1.1.1.21 purified enzyme in complex with inhibitor fidaresta, X-ray diffraction structure determination and analysis at 1.85 A resolution Sus scrofa

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.1.1.2 fidarestat interaction with the residues Tyr50, His113, Trp114 and Pro301 Sus scrofa
1.1.1.2 sorbinil
-
 Sus scrofa
1.1.1.21 (2R,4S)-6-fluoro-2',5'-dioxospiro-[chroman-4,4'-imidazoline]-2-carboxamide IC50: 570 nM, mechanism, active site binding modeling, the stereochemistry of the exocyclic amide group influences the affinity for the enzyme Sus scrofa
1.1.1.21 fidarestat 2S4S-eantiomer, i.e. (2S,4S)-6-fluoro-2',5'-dioxospiro-[chroman-4,4'-imidazoline]-2-carboxamide, IC50: 35 nM, binding site structure, binding to the enzyme does not induce conformational changes in the C-loop region, mechanism, active site binding modeling, the stereochemistry of the exocyclic amide group influences the affinity for the enzyme Sus scrofa
1.1.1.21 minalrestat cyclic imide inhibitor, mechanism, binds to ALR2 with its isoquinoline ring system located in a hydrophobic pocket formed mainly by the side chains of Trp20, Phe122, and Trp219 Sus scrofa
1.1.1.21 sorbinil aldose reductase inhibitor, IC50: 900 nM Sus scrofa
1.1.1.21 Tolrestat potent inhibition, mechanism involves residues Arg312, Leu300, and Phe122 Sus scrofa

Organism

EC Number Organism UniProt Comment Textmining
1.1.1.2 Sus scrofa
-
-
-
1.1.1.21 Sus scrofa
-
-
-

Source Tissue

EC Number Source Tissue Comment Organism Textmining
1.1.1.2 kidney
-
 Sus scrofa
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.1.1.2 DL-glyceraldehyde + NADPH + H+
-
 Sus scrofa glycerol + NADP+
-
 ?
1.1.1.21 additional information the enzyme catalyzes the NADPH-dependent reduction of aldehydes, xenobiotic aldehydes, ketones, trioses, and triose phosphates Sus scrofa ?
-
 ?

Synonyms

EC Number Synonyms Comment Organism
1.1.1.2 ALR1
-
 Sus scrofa
1.1.1.21 aldose reductase
-
 Sus scrofa
1.1.1.21 ALR2
-
 Sus scrofa

Cofactor

EC Number Cofactor Comment Organism Structure
1.1.1.2 NADPH
-
 Sus scrofa
1.1.1.21 NADPH dependent on Sus scrofa

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
1.1.1.21 0.000035
-
 2S4S-eantiomer, i.e. (2S,4S)-6-fluoro-2',5'-dioxospiro-[chroman-4,4'-imidazoline]-2-carboxamide, IC50: 35 nM, binding site structure, binding to the enzyme does not induce conformational changes in the C-loop region, mechanism, active site binding modelin Sus scrofa fidarestat
1.1.1.21 0.00057
-
 IC50: 570 nM, mechanism, active site binding modeling, the stereochemistry of the exocyclic amide group influences the affinity for the enzyme Sus scrofa (2R,4S)-6-fluoro-2',5'-dioxospiro-[chroman-4,4'-imidazoline]-2-carboxamide
1.1.1.21 0.0009
-
 aldose reductase inhibitor, IC50: 900 nM Sus scrofa sorbinil