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C298A
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
C303D
introduction of residue from binding pocket of isoform ALR1 into ALR2, analysis of binding properties of inhibitors
F115Y
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stable and active
F121P
introduction of residue from binding pocket of isoform ALR1 into ALR2, analysis of binding properties of inhibitors
G213P
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
G213S
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
L300A
introduction of residue from binding pocket of isoform ALR1 into ALR2, analysis of binding properties of inhibitors
L301M
introduction of residue from binding pocket of isoform ALR1 into ALR2, analysis of binding properties of inhibitors
R268A
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site-directed mutagenesis, the mutant shows similar kinetics for the aldehyde substrate, but highly reduced affinity for the nucleotide cofactor, and reduced activity compared to the wild-type enzyme
R293A
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
S210A
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
S214A
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
S226A
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
S302R
introduction of residue from binding pocket of isoform ALR1 into ALR2, analysis of binding properties of inhibitors
T113A
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stable and active
T113A/F115Y
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10fold decrease in kcat value, does not bind to inhibitor (5-chloro-2-[(4-cyanobenzyl)carbamoyl]phenoxy)acetic acid
T113V
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inhibition constants and vibrational frequencies of inhibitor (5-chloro-2-[(4-cyanobenzyl)carbamoyl]phenoxy)acetic acid in the active site
V301L
site-directed mutagenesis
V47I
introduction of residue from binding pocket of isoform ALR1 into ALR2, analysis of binding properties of inhibitors
W219A
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
W219E
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
C298S
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similar sensitivity against Cu2+ as wild-type
C298A/W219Y
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protein data bank: 1az1, structural analysis by molecular dynamics simulations
C298A/W219Y
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site-directed mutagenesis, altered kinetics and thermodynamics in phenylacetic acid derivative inhibitor binding compared to the wild-type enzyme
C298S
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similar sensitivity against Cu2+ as wild-type
C298S
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treatment with peroxynitrite does not significantly affect the catalytic activity of C298S, and enzyme is insensitive to dimedone
C303S
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insensitive to inactivation by CuCl2
C303S
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mutant is activated by peroxynitrite, and the peroxynitrite-modified protein is inhibited by dimedone
Y48H
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changing substrate selectivity
Y48H
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protein data bank: 2acu, structural analysis by molecular dynamics simulations
additional information
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construction of deletion mutant DELTA214-219 showing reduced activity compared to the wild-type enzyme
additional information
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enzyme inhibition by antisense ablation with siRNA prevents fibroblast growth factorinduced and platelet-derived growth factorinduced up-regulation of PGE2 synthesis in Caco-2 cells, overview, nude mice bearing SW480 human colon adenocarcinoma cells completely arrest tumor progression
additional information
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enzyme overexpression prevents the lipid aldehyde-induced activation of caspase-3, p38 MAPK, JNK, and the expression of Bcl-2 family proteins in lens epithelial cells
additional information
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genetic polymorphisms associated with the human aldose reductase gene have been found to be associated with diabetic complications
additional information
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the recombinnat enzyme regulates TGF-beta1-induced production of fibronectin and type IV collagen in transformed cultured rat mesangial cells, detailed overview
additional information
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transient transfection of Caco-2 cells with aldose reductase antisense but not scrambled antisense oligonucleotides abolishes aldose reductase protein by more than 95%. Antisense abolition significantly prevents the tumor necrosis factor alpha-induced prostaglandin E2 production in Caco-2 cells
additional information
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enzyme downregulation by specific AR-targeted siRNA transfection
additional information
construction of enzyme knockout, ARKO, mice and of mice overexpressing the human enzyme in a cardiospecific manner, i.e. MHC-hAR mice. Increased PPARgamma and reduced CEBPalpa expression occur in the nuclear fractions of MHC-hAR hearts compared to wild-type and ARKO, indicating increased PPARgamma to be the driving force for increased lipid accumulation by human recombinant enzyme
additional information
enzyme downregulation by siRNA expression
additional information
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enzyme downregulation by siRNA expression
additional information
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aldose reductase overexpression causes strong suppression of peroxisome proliferator-activated receptor alpha/delta activity together with significant down-regulation of mRNA expression for acetyl-CoA oxidase and carnitine palmitoyltransferase-1. Suppressive effects are attenuated by the selective aldose reductase inhibitor zopolrestat. Aldose reductase overexpression greatly increases the levels of phosphorylated peroxisome proliferator-activated receptor alpha and ERK1/2. Aldose reductase-induced suppression of peroxisome proliferator-activated receptor alpha activity is attenuated by treatment with an inhibitor for ERK1/2 but not that for phosphoinositide 3-kinase, p38, or JNK
additional information
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inhibition or RNA interference ablation of aldose reductase suppresses lipopolysaccharide-stimulated production of nitric oxide and over-expression of inducible nitric oxide synthase. Inhibition also prevents the lipopolysaccaride-induced apoptosis, cell cycle arrest, activation of caspase-3, downregulation of Bcl-xl and up-regulation of Bax and Bak in macrophages
additional information
construction of enzyme knockout mutant mice
additional information
recombinant enzyme overexpression elevates RMG activation in retina
additional information
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recombinant enzyme overexpression elevates RMG activation in retina
additional information
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construction of enzyme knockout mutant mice
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additional information
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recombinant enzyme overexpression elevates RMG activation in retina
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additional information
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mutation of residues Trp111, His110, Tyr48 or Trp20 leads to a significant reduction in aldose reductase activity