Publications

• Structure of rat aldose reductase-like protein AKR1B14 holoenzyme: Probing the role of His269 in coenzyme binding by site-directed mutagenesis.

  Sundaram K., Dhagat U., Endo S., Chung R., Matsunaga T., Hara A., El-Kabbani O.

  Rat aldose reductase-like protein (AKR1B14) is the ortholog of mouse vas deferens protein (AKR1B7) playing roles in detoxification of reactive aldehydes and synthesis of prostaglandin F(2α). The crystal structure of the binary complex (AKR1B14-NADPH) was determined at 1.86Å resolution, and showed ... >> More

  Rat aldose reductase-like protein (AKR1B14) is the ortholog of mouse vas deferens protein (AKR1B7) playing roles in detoxification of reactive aldehydes and synthesis of prostaglandin F(2α). The crystal structure of the binary complex (AKR1B14-NADPH) was determined at 1.86Å resolution, and showed that the adenine ring and the 2'-phosphate group of the coenzyme formed π-stacking and electrostatic interactions with the imidazole ring and ND1 atom, respectively, of His269, which is not conserved in other aldose reductase-like proteins. The interactions were supported by site-directed mutagenesis of His269 to Arg, Phe and Met, which increased the K(m) for NADPH by 4, 7 and 127-fold, respectively. This is the first report of the tertiary structure of a rodent AKR1B7 ortholog, which describes the role of a novel dual interaction for the non-conserved His269 in coenzyme binding. << Less

  Bioorg. Med. Chem. Lett. 21:801-804(2011) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.

• Three genes whose expression is induced by stress in Saccharomyces cerevisiae.

  Garay-Arroyo A., Covarrubias A.A.

  In this work we report the isolation and characterization of three genes induced by different stress conditions in the yeast Saccharomyces cerevisiae. These genes, named GRE1, GRE2 and GRE3, were identified by the differential display technique using total RNAs obtained from yeast grown under hype ... >> More

  In this work we report the isolation and characterization of three genes induced by different stress conditions in the yeast Saccharomyces cerevisiae. These genes, named GRE1, GRE2 and GRE3, were identified by the differential display technique using total RNAs obtained from yeast grown under hyperosmotic conditions. Northern analysis of RNA obtained from different growth conditions shows that their corresponding transcripts accumulate not only in response to osmotic stress but also to ionic, oxidative and heat stress. Analysis of the deduced amino acid sequences indicated that GRE1, GRE2 and GRE3 correspond to ORFs YPL223C, YOL151W and YHR104W, respectively. Additionally, it suggested that GRE1 encodes a hydrophilic polypeptide that it is not homologous to any known protein but has features resembling the late embryogenesis abundant (LEA) proteins characterized in higher plants; GRE2 encodes a putative reductase with similarity to plant dihydroflavonol-4-reductases; and GRE3 codifies for a keto-aldose reductase highly related to fungal xylose-reductases. The three genes are induced in the late growth phases in agreement with the presence of PDS elements in their promoter regions. The three of them are under the control of the HOG pathway, even though GRE1 and GRE2 promoter regions do not present the consensus core STRE sequence. In addition, GRE1 and GRE3 are regulated negatively by the cAMP-PKA transduction pathway and positively by the transcriptional factors Msn2p and Msn4p. Gene disruptions of the GRE genes did not show a phenotype in any of the tested stress conditions. << Less

  Yeast 15:879-892(1999) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.

• Purification and partial characterization of an aldo-keto reductase from Saccharomyces cerevisiae.

  Kuhn A., van Zyl C., van Tonder A., Prior B.A.

  A cytosolic aldo-keto reductase was purified from Saccharomyces cerevisiae ATCC 26602 to homogeneity by affinity chromatography, chromatofocusing, and hydroxylapatite chromatography. The relative molecular weights of the aldo-keto reductase as determined by sodium dodecyl sulfate-polyacrylamide ge ... >> More

  A cytosolic aldo-keto reductase was purified from Saccharomyces cerevisiae ATCC 26602 to homogeneity by affinity chromatography, chromatofocusing, and hydroxylapatite chromatography. The relative molecular weights of the aldo-keto reductase as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and size exclusion chromatography were 36,800 and 35,000, respectively, indicating that the enzyme is monomeric. Amino acid composition and N-terminal sequence analysis revealed that the enzyme is closely related to the aldose reductases of xylose-fermenting yeasts and mammalian tissues. The enzyme was apparently immunologically unrelated to the aldose reductases of other xylose-fermenting yeasts. The aldo-keto reductase is NADPH specific and catalyzes the reduction of a variety of aldehydes. The best substrate for the enzyme is the aromatic aldehyde p-nitrobenzaldehyde (Km = 46 microM; kcat/Km = 52,100 s-1 M-1), whereas among the aldoses, DL-glyceraldehyde was the preferred substrate (Km = 1.44 mM; kcat/Km = 1,790 s-1 M-1). The enzyme failed to catalyze the reduction of menadione and p-benzoquinone, substrates for carbonyl reductase. The enzyme was inhibited only slightly by 2 mM sodium valproate and was activated by pyridoxal 5'-phosphate. The optimum pH of the enzyme is 5. These data indicate that the S. cerevisiae aldo-keto reductase is a monomeric NADPH-specific reductase with strong similarities to the aldose reductases. << Less

  Appl. Environ. Microbiol. 61:1580-1585(1995) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.

• Rat aldose reductase-like protein (AKR1B14) efficiently reduces the lipid peroxidation product 4-oxo-2-nonenal.

  Endo S., Matsunaga T., Fujita A., Tajima K., El-Kabbani O., Hara A.

  In this study, we examined the substrate specificity, inhibitor sensitivity and kinetic mechanism of a rat aldose reductase-like protein, which is named AKR1B14 in the aldo-keto reductase (AKR) superfamily. AKR1B14 catalyzed the nicotinamide adenine dinucleotide phosphate reduced form (NADPH)-depe ... >> More

  In this study, we examined the substrate specificity, inhibitor sensitivity and kinetic mechanism of a rat aldose reductase-like protein, which is named AKR1B14 in the aldo-keto reductase (AKR) superfamily. AKR1B14 catalyzed the nicotinamide adenine dinucleotide phosphate reduced form (NADPH)-dependent reduction of carbonyl compounds (derived from lipid peroxidation and glycation), xenobiotic aromatic aldehydes and some aromatic ketones. 4-Oxo-2-nonenal, the best substrate showing a K(m) value of 0.16 µM, was reduced into less reactive 4-oxo-2-nonenol, and its cytotoxicity was attenuated by the overexpression of the enzyme in cultured cells. The enzyme also showed low K(m) values (0.9-10 µM) for medium-chain aliphatic aldehydes (such as 4-hydroxynonenal, 1-hexenal and farnesal) and 3-deoxyglucosone, although the K(m) values for short-chain substrates (such as isocaproaldehyde, acrolein and methylglyoxal) were high (16-600 µM). In the reverse reaction, aliphatic and aromatic alcohols were oxidized by AKR1B14 at low rates. AKR1B14 was inhibited by aldose reductase inhibitors such as tolrestat and epalrestat, and their inhibition patterns were noncompetitive versus the aldehyde substrate and competitive with respect to the alcohol substrate. Kinetic analyses of the oxidoreduction and dead-end inhibition suggest that the reaction follows an ordered sequential mechanism. << Less

  Biol. Pharm. Bull. 33:1886-1890(2010) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.

• Purification and properties of calf liver aldose reductase.

  Attwood M.A., Doughty C.C.

  Biochim Biophys Acta 370:358-368(1974) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.

• [Aldose reductase].

  HERS H.G.

  Biochim Biophys Acta 37:120-126(1960) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.