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Literature summary for 1.1.1.21 extracted from

  • Steuber, H.; Zentgraf, M.; Podjarny, A.; Heine, A.; Klebe, G.
    High-resolution crystal structure of aldose reductase complexed with the novel sulfonyl-pyridazinone inhibitor exhibiting an alternative active site anchoring group (2006), J. Mol. Biol., 356, 45-56.
    View publication on PubMed

Crystallization (Commentary)

Crystallization (Comment) Organism
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 Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
6-[(5-chloro-3-methyl-1-benzofuran-2-yl)sulfonyl]pyridazin-3(2H)-one binding structure, inhibition mechanism, residues Trp111, His110, Thr113, Tyr48, Trp20, and Phe122, and the residues of the C-terminal loop Ala299, Leu300, Leu301, Ser302, Cys303 are involved, overview Homo sapiens
fidarestat complex formation with the enzyme Homo sapiens
IDD 594 binding structure, inhibition mechanism, overview Homo sapiens
minalrestat complex formation with the enzyme Homo sapiens
sorbinil complex formation with the enzyme Homo sapiens
Tolrestat
-
Homo sapiens

Molecular Weight [Da]

Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
36000
-
x * 36000, ALR2 is a TIM-barrel-shpaped aldo-keto reductase with a C-terminal loop, residues Ala299, Leu300, Leu301, Ser302, Cys303, involved in substrate and inhibitor binding Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
aldose + NADPH + H+ Homo sapiens first and rate-limiting step in the polyol pathway alditol + NADP+
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens P15121
-
-

Reaction

Reaction Comment Organism Reaction ID
alditol + NAD(P)+ = aldose + NAD(P)H + H+ reaction mechanism, catalytic residues are Tyr48, Lys77, and His110, C-terminal loop residues Ala299, Leu300, Leu301, Ser302, Cys303 are involved in substrate and inhibitor binding Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
aldose + NADPH + H+
-
Homo sapiens alditol + NADP+
-
?
aldose + NADPH + H+ first and rate-limiting step in the polyol pathway Homo sapiens alditol + NADP+
-
?

Subunits

Subunits Comment Organism
? x * 36000, ALR2 is a TIM-barrel-shpaped aldo-keto reductase with a C-terminal loop, residues Ala299, Leu300, Leu301, Ser302, Cys303, involved in substrate and inhibitor binding Homo sapiens

Synonyms

Synonyms Comment Organism
aldose reductase
-
Homo sapiens
ALR2
-
Homo sapiens

Cofactor

Cofactor Comment Organism Structure
NADPH
-
Homo sapiens