Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: HUMANGGP:026099 (oxidoreductase)
 7,952 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lysine-ketoglutarate reductase (EC. 1.5.1.8) deficiency in skin fibroblasts has been previously reported in patients with familial hyperlysinemia, providing an adequate explanation for the biochemical derangements noted clinically. In the present study, analysis of liver obtained at autopsy from a patient with familial hyperlysinemia confirmed the lysine-ketoglutarate reductase deficiency but, unexpectedly, also revealed an absence of saccharopine dehydrogenase (EC. 1.5.1.9) and saccharopine oxidoreductase activity. Skin fibroblasts from two siblings with the disease and a third patient from an unrelated family were also deficient in all three enzymes (lysine-ketoglutarate reductase, average 9%; saccharopine dehydrogenase, average 4%; saccharopine oxidoreductase, less than 10% of normal). The possibility that saccharopine dehydrogenase is a substrate-inducible enzyme was investigated by maintaining normal skin fibroblasts in a medium with minimal lysine concentration, and exposing hyperlysinemic fibroblasts to elevated saccharopine concentrations. There was no significant modification in saccharopine dehydrogenase activity.
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PMID:Multiple enzyme defects in familial hyperlysinemia. 93 35

Biotransformations were developed to oxidize N epsilon-carbobenzoxy(CBZ)-L-lysine and to reduce the product keto acid to L-CBZ-oxylysine. Lysyl oxidase (L-lysine: O2 oxidoreductase, EC 1.4.3.14) from Trichoderma viride was relatively specific for L-lysine and had very low activity with N epsilon-substituted derivatives. L-Amino acid oxidase (L-amino acid: O2 oxidoreductase [deaminating], EC 1.4.3.2) from Crotalus adamanteus venom had low activity with L-lysine but high activity with N epsilon-formyl-, t-butyoxycarbonyl(BOC)-, acetyl-, trifluoroacetyl-, or CBZ-L-lysine. L-2-Hydroxyisocaproate dehydrogenase (EC 1.1.1.-) from Lactobacillus confusus catalyzed the reduction by NADH of the keto acids from N epsilon-acetyl-, trifluoroacetyl-, formyl- and CBZ-L-lysine but was inactive with the products from oxidation of L-lysine, L-lysine methyl ester, L-lysine ethyl ester or N epsilon-t-BOC-L-lysine. Providencia alcalifaciens (SC9036, ATCC 13159) was a good microbial substitute for the snake venom oxidase and also provided catalase (H2O2:H2O2 oxidoreductase EC 1.11.1.6). N epsilon-CBZ-L-Lysine was converted to CBZ-L-oxylysine in 95% yield with 98.5% optical purity by oxidation using P. alcalifaciens cells followed by reduction of the keto acid using L-2-hydroxyisocaproate dehydrogenase. NADH was regenerated using formate dehydrogenase (formate: NAD oxidoreductase, EC 1.2.1.2) from Candida boidinii. The Providencia oxidase was localized in the particulate fraction and catalase activity was predominantly in the soluble fraction of sonicated cells. The pH optima and kinetic constants were determined for the reactions.
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PMID:Transformation of N epsilon-CBZ-L-lysine to CBZ-L-oxylysine using L-amino acid oxidase from Providencia alcalifaciens and L-2-hydroxy-isocaproate dehydrogenase from Lactobacillus confusus. 136 13

L-Lysine epsilon-dehydrogenase [L-lysine:NADP+ oxidoreductase (epsilon-deaminating), EC 1.4.1.15] of Candida albicans was studied emphasizing its application for the production of alpha-aminoadipate-delta-semialdehyde and related compounds. A high enzyme level (240 pkat/mg of protein in the crude extract) could be attained during growth in the presence of L-lysine as sole nitrogen source. After optimization of the reaction conditions a partial purified enzyme (1.5 nkat/mg of protein) was used to produce alpha-aminoadipate-delta-semialdehyde, S-(beta-acetaldehyde)-cysteine, alpha-amino-delta-hydroxyadipate-semialdehyde and alpha-amino-gamma-hydroxyadipate-semialdehyde from the corresponding substrates lysine, S-(beta-aminoethyl)-cysteine, 5-hydroxylysine and 4-hydroxylysine, respectively. After purification of the compounds using Dowex 50 x 4 chromatography a yield of the products between 4.6 and 6.8% was achieved.
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PMID:Enzymatic production of alpha-aminoadipate-delta-semialdehyde and related compounds by lysine epsilon-dehydrogenase from Candida albicans. 150 28

The secondary structure of Pseudomonas cytochrome c peroxidase (ferrocytochrome c: hydrogen-peroxide oxidoreductase, EC 1.11.1.5) has been predicted from the established amino acid sequence of the enzyme using a Chou-Fasman-type algorithm. The amount of alpha-helicity thus obtained is in agreement with previously obtained results based on circular dichroic measurements at far UV. The two heme c moieties of the enzyme have earlier been shown to have widely different characteristics, e.g., the redox potentials of the hemes differ with about 600 mV, and carry out different functions in the enzyme molecule. The structural comparisons made in this study enlighten the observed functional differences. The first heme in the polypeptide chain, heme 1, has in its environment a folding pattern generally encountered in cytochromes. In the region of the sixth ligand, however, profound differences are noted. The cytochromal methionine has been replaced by a lysine with a concomitant lowering of redox-potential thus making peroxidatic activity possible. Around heme 2, extra amino acid residues have been added to the peroxidase as compared with Rhodospirillum molischianum cytochrome c2 core structure in the 20's loop. After completion of the cytochromal fold around heme 2 an additional tail consisting of 25 residues is linked. This tail shows no stabilizing elements of secondary structure, but contains a strongly hydrophobic segment which suggests a possible membrane contact site of this extrinsic membrane protein. Heme 2 is concluded to have a cytochromal function in the molecule. To further elucidate the functional properties of the enzyme, a noncovalent two-fragment complex was produced by specific cleavage of the peroxidase by Pseudomonas elastase. The complex was studied with respect to its properties to the native enzyme. The two-fragment complex of Pseudomonas peroxidase retains the overall conformation of the native enzyme showing, however, no heme-heme interaction. Thus, a comparison of the properties of the native enzyme with those of the two-fragment complex permitted some conclusions to be drawn on the structure of the enzyme as well as the mechanism of heme-heme interaction. From the present results we conclude that the two distal heme surfaces in the peroxidase are oriented toward each other. This structural arrangement allows an inter-heme communication in the enzyme molecule and it also forms the structural basis for the enzyme mechanism. The structural comparisons also give insight into the evolution of an ancestral cytochrome c into an efficient peroxidase that has a versatile control mechanism in heme-heme interaction.
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PMID:Structural and functional features of Pseudomonas cytochrome c peroxidase. 165 79

The quinoprotein methanol dehydrogenase (MDH) of Acetobacter methanolicus has an alpha 2 beta 2 structure. By contrast with other MDHs, the beta-subunit (approx. 8.5 kDa) does not contain the five lysine residues previously proposed to be involved in ionic interactions with the electron acceptor cytochrome cL. That electrostatic interactions are involved was confirmed by the demonstration that methanol:cytochrome cL oxidoreductase activity was inhibited by high ionic strength (I), the strength of interaction being inversely related to the square root of I. Specific modifiers of arginine residues on MDH inhibited this reaction but not the dye-linked MDH activity. Modification of lysine residues on MDH that altered its charge had no effect on the dye-linked activity but inhibited reaction with cytochrome cL. When the charge was retained on modification of lysine residues, little effect on either activity was observed. Cross-linking experiments confirmed that lysine residues on the alpha-subunit, but not the beta-subunit, are involved in the 'docking' process between the proteins.
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PMID:The interaction of methanol dehydrogenase and cytochrome cL in the acidophilic methylotroph Acetobacter methanolicus. 166 Feb 63

Rat liver 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD, EC 1.1.1.50) is an NAD(P)(+)-dependent oxidoreductase which will terminate androgen action by converting 5 alpha-dihydrotestosterone to 3 alpha-androstanediol. It is identical to dihydrodiol dehydrogenase and it can function as a 9-, 11-, and 15-hydroxyprostaglandin dehydrogenase. Its reactions are potently inhibited by the nonsteroidal anti-inflammatory drugs (NSAIDs). A cDNA (2.1 kilobases) for 3 alpha-HSD was cloned from a rat liver cDNA expression library in lambda gt11. Portions of the cDNA insert which contained an internal EcoRI site were subcloned into pGEM3, and dideoxysequencing revealed that the cDNA contains an open reading frame of 966 nucleotides which encode a protein of 322 amino acids with a monomer Mr of 37,029. The identity of this clone was confirmed by locating two tryptic peptides and two endoproteinase Lys-C peptides from purified 3 alpha-HSD within the nucleotide sequence. The amino acid sequence of rat liver 3 alpha-HSD bears no significant homology with 3 beta-, 17 beta- or 11 beta-hydroxysteroid dehydrogenases but has striking homology with bovine lung prostaglandin F synthase (69% homology at the amino acid level and 74% homology at the nucleotide level) which is a member of the aldehyde/aldose reductase family. This sequence homology supports previous correlates which suggest that in rat 3 alpha-HSD may represent an important target for NSAIDs. The nucleotide sequence also contains three peptides that have been identified by affinity labeling with either 3 alpha-bromoacetoxyandrosterone (substrate analog) or 11 alpha-bromoacetoxyprogesterone (glucocorticoid analog) to comprise the active site (see accompanying article (Penning, T. M., Abrams, W. R., and Pawlowski, J. E. (1991) J. Biol. Chem. 266, 8826-8834]. The sequence data presented suggests that 3 alpha-HSD, prostaglandin F synthase, and aldehyde/aldose reductases are members of a common gene family.
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PMID:Cloning and sequencing of the cDNA for rat liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase. 184 Jun 1

The covalent structure of bovine lens aldose reductase (alditol-NADP+ oxidoreductase, EC 1.1.1.21) was determined by sequence analysis of peptides generated by specific and chemical cleavage of the homogeneous apoenzyme. Peptides, purified by reverse-phase high performance liquid chromatography were subjected to compositional analysis and sequencing by gas-phase automated Edman degradation. Aldose reductase was found to contain 315 amino acid residues. The enzyme is blocked at the amino terminus, and mass spectrometry was employed to identify the blocking acetyl group and to sequence the amino-terminal tryptic peptide. The aldose reductase was shown to contain no carbohydrate despite the fact that the enzyme contains the consensus sequence -Asn-Lys-Thr- for N-linked glycosylation. Comparative sequence analysis and application of algorithms for prediction of secondary structure and nucleotide binding domains are consistent with the view that aldose reductase is a double-domain protein with a beta-alpha-beta secondary structural organization. The NADPH binding site appears to be associated with the amino-terminal half of the enzyme. Modeling studies based on the tertiary structures of dihydrofolate and glutathione reductases indicate that the NADPH binding site begins at Lys-11 and continues with a beta-alpha-beta fold characteristic of nucleotide binding proteins.
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PMID:Sequence analysis of bovine lens aldose reductase. 210 51

N5-(L-1-Carboxyethyl)-L-ornithine:NADP+ oxidoreductase (EC 1.5.1.-) from Streptococcus lactis K1 has been purified 8,000-fold to homogeneity. The NADPH-dependent enzyme mediates the reductive condensation between pyruvic acid and the delta- or epsilon-amino groups of L-ornithine and L-lysine to form N5-(L-1-carboxyethyl)-L-ornithine and N6-(L-1-carboxyethyl)-L-lysine, respectively. The five-step purification procedure involves ion-exchange (DE52 and phosphocellulose P-11), gel filtration (Ultrogel AcA 44), and affinity chromatography (2',5'-ADP-Sepharose 4B). Approximately 100-200 micrograms of purified enzyme of specific activity 40 units/mg were obtained from 60 g of cells, wet weight. Anionic polyacrylamide gel electrophoresis revealed a single enzymatically active protein band, whereas three species (pI 4.8-5.1) were detected by analytical electrofocusing. The purified enzyme is active over a broad pH range of 6.5-9.0 and is stable to heating at 50 degrees C for 10 min. Substrate Km values were determined to be: NADPH, 6.6 microM; pyruvate, 150 microM; ornithine, 3.3 mM; and lysine, 18.2 mM. The oxidoreductase has a relative molecular mass (Mr = 150,000) as estimated by high pressure liquid chromatography exclusion chromatography and by polyacrylamide gradient gel electrophoresis. Conventional gel filtration indicated an Mr = 78,000, and a single protein band of Mr = 38,000 was revealed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme is composed of identical subunits of Mr = 38,000, which may associate to yield both dimeric and tetrameric forms. Polyclonal antibody to the purified protein inhibited enzyme activity. The amino acid composition of the enzyme is reported, and the sequence of the first 37 amino acids from the NH2 terminus has been determined by stepwise Edman degradation.
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PMID:N5-(L-1-carboxyethyl)-L-ornithine:NADP+ oxidoreductase from Streptococcus lactis. Purification and partial characterization. 249 34

Prolyl 4-hydroxylase [procollagen-proline, 2-oxyglutarate 4-dioxygenase; procollagen-L-proline, 2-oxoglutarate:oxygen oxidoreductase (4-hydroxylating), EC 1.14.11.2], an alpha 2 beta 2 tetramer, catalyzes the formation of 4-hydroxyproline in collagens by the hydroxylation of proline residues in peptide linkages. We report here on the isolation of cDNA clones encoding the alpha-subunit of the enzyme from human tumor HT-1080, placenta, and fibroblast cDNA libraries. Eight overlapping clones covering almost all of the corresponding 3000-nucleotide mRNA, including all the coding sequences, were characterized. These clones encode a polypeptide of 517 amino acid residues and a signal peptide of 17 amino acids. Previous characterization of cDNA clones for the beta-subunit of prolyl 4-hydroxylase has indicated that its C terminus has the amino acid sequence Lys-Asp-Glu-Leu, which, it has been suggested, is necessary for the retention of a polypeptide within the lumen of the endoplasmic reticulum. The alpha-subunit does not have this C-terminal sequence, and thus one function of the beta-subunit in the prolyl 4-hydroxylase tetramer appears to be to retain the enzyme within this cell organelle. Interestingly, three of the cDNA clones for the alpha-subunit contained a 64-nucleotide sequence homologous but not identical to the corresponding 64-nucleotide sequence found in four other cDNA clones. Nuclease S1 mapping experiments demonstrated that this difference was due to the existence of two types of mRNA present in approximately equal amounts. Southern blot analyses of human genomic DNA with a cDNA probe for the alpha-subunit suggested the presence of only one gene encoding the two types of mRNA, which appear to result from mutually exclusive alternative splicing of primary transcripts of one gene.
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PMID:Molecular cloning of the alpha-subunit of human prolyl 4-hydroxylase: the complete cDNA-derived amino acid sequence and evidence for alternative splicing of RNA transcripts. 254 75

Two-dimensional 1H NMR spectroscopy has been applied to a structural analysis of the reduced form of a recombinant human thioredoxin, a ubiquitous dithiol oxidoreductase recently isolated from an immunocompetent lymphoblastoid cell line. The sequential assignment of the spectrum, including all proline residues, has been accomplished by using experiments to demonstrate through-bond and through-space connectivities. The secondary structure has been determined by a qualitative interpretation of nuclear Overhauser effects, NH exchange data, and 3JHN alpha coupling constants. The secondary structure was found to be similar to that of the X-ray structure of Escherichia coli thioredoxin, consisting of a mixed five-stranded beta-sheet surrounded by four alpha-helices. The assignment and structural characterization of human thioredoxin was facilitated by the increased resolution and sensitivity afforded by a magnetic field strength of 600 MHz and required the use of two temperatures and two pH conditions to resolve ambiguities caused by a duplication of resonances. This duplication, extending from Phe-41 to Val-59, and including Lys-3-Ile-5, Val-24, Val-25, Asn-39, and Ile-101-Glu-103, appears to be due to heterogeneity arising from the presence or absence of the N-terminal methionine.
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PMID:A proton nuclear magnetic resonance assignment and secondary structure determination of recombinant human thioredoxin. 268 71


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