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Edmund Maser - One of the best experts on this subject based on the ideXlab platform.
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Carbonyl Reductases and pluripotent hydroxysteroid dehydrogenases of the short-chain dehydrogenase/Reductase superfamily.
Drug metabolism reviews, 2007Co-Authors: Frank Hoffmann, Edmund MaserAbstract:Carbonyl reduction of aldehydes, ketones, and quinones to their corresponding hydroxy derivatives plays an important role in the phase I metabolism of many endogenous (biogenic aldehydes, steroids, prostaglandins, reactive lipid peroxidation products) and xenobiotic (pharmacologic drugs, carcinogens, toxicants) compounds. Carbonyl-reducing enzymes are grouped into two large protein superfamilies: the aldo-keto Reductases (AKR) and the short-chain dehydrogenases/Reductases (SDR). Whereas aldehyde Reductase and aldose Reductase are AKRs, several forms of carbonyl Reductase belong to the SDRs. In addition, there exist a variety of pluripotent hydroxysteroid dehydrogenases (HSDs) of both superfamilies that specifically catalyze the oxidoreduction at different positions of the steroid nucleus and also catalyze, rather nonspecifically, the reductive metabolism of a great number of nonsteroidal carbonyl compounds. The present review summarizes recent findings on carbonyl Reductases and pluripotent HSDs of the SDR protein superfamily.
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carbonyl Reductases and pluripotent hydroxysteroid dehydrogenases of the short chain dehydrogenase Reductase superfamily
Drug Metabolism Reviews, 2007Co-Authors: Frank Hoffmann, Edmund MaserAbstract:Carbonyl reduction of aldehydes, ketones, and quinones to their corresponding hydroxy derivatives plays an important role in the phase I metabolism of many endogenous (biogenic aldehydes, steroids, prostaglandins, reactive lipid peroxidation products) and xenobiotic (pharmacologic drugs, carcinogens, toxicants) compounds. Carbonyl-reducing enzymes are grouped into two large protein superfamilies: the aldo-keto Reductases (AKR) and the short-chain dehydrogenases/Reductases (SDR). Whereas aldehyde Reductase and aldose Reductase are AKRs, several forms of carbonyl Reductase belong to the SDRs. In addition, there exist a variety of pluripotent hydroxysteroid dehydrogenases (HSDs) of both superfamilies that specifically catalyze the oxidoreduction at different positions of the steroid nucleus and also catalyze, rather nonspecifically, the reductive metabolism of a great number of nonsteroidal carbonyl compounds. The present review summarizes recent findings on carbonyl Reductases and pluripotent HSDs of the SDR protein superfamily.
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Reductive metabolism of metyrapone by a quercitrin-sensitive ketone Reductase in mouse liver cytosol.
Biochemical Pharmacology, 1991Co-Authors: Edmund Maser, K.j. NetterAbstract:: Mouse liver cytosol catalyses the reduction of metyrapone to the corresponding alcohol metabolite metyrapol. The enzyme involved was characterized as a NADPH-dependent carbonyl Reductase which is strongly inhibited by the plant flavonoid quercitrin but which shows no sensitivity to phenobarbital. Thus, by inhibitor subdivision of carbonyl Reductases the metyrapone Reductase in mouse liver cytosol has to be classified as a ketone Reductase rather than an aldehyde Reductase, as it was shown previously for the analogous enzyme in mouse liver microsomes based on the same pattern of inhibitor classification. Moreover, immunological comparison of the metyrapone Reductases from the two subcellular fractions reveal no common antigenic determinants indicating the structural difference between these enzymes. In conclusion, metyrapone undergoes reductive biotransformation mediated by two clearly distinct carbonyl Reductases located in different subcellular compartments of mouse liver cells. Considering the convenient and sensitive HPLC-method for direct metyrapol determination, metyrapone may serve as a useful tool in the investigation of these enzymes, although their physiological roles remain to be determined.
Hans G. Trüper - One of the best experts on this subject based on the ideXlab platform.
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29 reverse siroheme sulfite Reductase from thiobacillus denitrificans
Methods in Enzymology, 1994Co-Authors: Hans G. TrüperAbstract:Publisher Summary This chapter describes reverse siroheme sulfite Reductase from Thiobacillus denitrificans (T. denitrificans). Adenylylsulfate Reductase has been found to occur only in the anaerobe T. denitrificans and in the aerobes Thiobacillus thioparus and “Thiobacillus” thiooxidans. A siroheme-containing sulfite Reductase in high intracellular concentration is found in T. denitrificans. In contrast to the sulfite Reductases in sulfate-reducing bacteria (SRB), in T. denitrificans the enzyme must function in the oxidative—or “reverse”—direction, oxidizing sulfane sulfur to sulfite. Sulfite Reductase is measured in a manometric assay in the direction of sulfite reduction with enzymatically reduced methyl viologen as electron donor. The reduction of methyl viologen by hydrogen gas is catalyzed by purified hydrogenase from Desulfovibrio gigas. The consumption of hydrogen is recorded manometrically. The enzyme contains 24 mol of iron and 20 mol of (acid-labile) sulfur per mole of enzyme and can reduce sulfite, but not thiosulfate, dithionate, trithionate, or tetrathionate. Unlike assimilatory sulfite Reductases the enzyme does not contain flavin groups.
Frank Hoffmann - One of the best experts on this subject based on the ideXlab platform.
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carbonyl Reductases and pluripotent hydroxysteroid dehydrogenases of the short chain dehydrogenase Reductase superfamily
Drug Metabolism Reviews, 2007Co-Authors: Frank Hoffmann, Edmund MaserAbstract:Carbonyl reduction of aldehydes, ketones, and quinones to their corresponding hydroxy derivatives plays an important role in the phase I metabolism of many endogenous (biogenic aldehydes, steroids, prostaglandins, reactive lipid peroxidation products) and xenobiotic (pharmacologic drugs, carcinogens, toxicants) compounds. Carbonyl-reducing enzymes are grouped into two large protein superfamilies: the aldo-keto Reductases (AKR) and the short-chain dehydrogenases/Reductases (SDR). Whereas aldehyde Reductase and aldose Reductase are AKRs, several forms of carbonyl Reductase belong to the SDRs. In addition, there exist a variety of pluripotent hydroxysteroid dehydrogenases (HSDs) of both superfamilies that specifically catalyze the oxidoreduction at different positions of the steroid nucleus and also catalyze, rather nonspecifically, the reductive metabolism of a great number of nonsteroidal carbonyl compounds. The present review summarizes recent findings on carbonyl Reductases and pluripotent HSDs of the SDR protein superfamily.
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Carbonyl Reductases and pluripotent hydroxysteroid dehydrogenases of the short-chain dehydrogenase/Reductase superfamily.
Drug metabolism reviews, 2007Co-Authors: Frank Hoffmann, Edmund MaserAbstract:Carbonyl reduction of aldehydes, ketones, and quinones to their corresponding hydroxy derivatives plays an important role in the phase I metabolism of many endogenous (biogenic aldehydes, steroids, prostaglandins, reactive lipid peroxidation products) and xenobiotic (pharmacologic drugs, carcinogens, toxicants) compounds. Carbonyl-reducing enzymes are grouped into two large protein superfamilies: the aldo-keto Reductases (AKR) and the short-chain dehydrogenases/Reductases (SDR). Whereas aldehyde Reductase and aldose Reductase are AKRs, several forms of carbonyl Reductase belong to the SDRs. In addition, there exist a variety of pluripotent hydroxysteroid dehydrogenases (HSDs) of both superfamilies that specifically catalyze the oxidoreduction at different positions of the steroid nucleus and also catalyze, rather nonspecifically, the reductive metabolism of a great number of nonsteroidal carbonyl compounds. The present review summarizes recent findings on carbonyl Reductases and pluripotent HSDs of the SDR protein superfamily.
Richard Haser - One of the best experts on this subject based on the ideXlab platform.
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Encyclopedia of Inorganic and Bioinorganic Chemistry - Trimethylamine N‐Oxide Reductase
Encyclopedia of Inorganic and Bioinorganic Chemistry, 2011Co-Authors: Chantal Iobbi-nivol, Richard Haser, Vincent Méjean, Mirjam CzjzekAbstract:Trimethylamine N-oxide (TMAO) is a compound widely distributed in marine fish and invertebrates; and TMAO reducing enzymes are found not only in marine bacteria and photosynthetic bacteria living in ponds but also in enterobacteria. The various respiratory systems reducing TMAO, described so far, share a high level of homology either in their general structure, or in the regulation or mechanism of electron transfer. According to their content of molybdenum cofactor, the enzymes in charge of TMAO reduction are classified in the structural dimethylsulfoxide (DMSO) Reductase family. TMAO Reductases, however, in contrast to DMSO Reductases are highly specific enzymes and reduce only their physiological substrate. The crystal structure was determined for the TMAO Reductase from Shewanella massilia, and its structural differences with DMSO Reductases in the environment of the active site. A tyrosine residue in the proximity of the molybdenum ion in DMSO Reductases is absent in TMAO Reductases and could be related to the differences in substrate specificities. 3D Structure Keywords: trimethylamine N-oxide Reductase; oxomolybdenum enzymes; substrate specificity; crystal structure; marine bacteria
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Crystal structure of oxidized trimethylamine N-oxide Reductase from Shewanella massilia at 2.5 å resolution
Journal of molecular biology, 1998Co-Authors: Mirjam Czjzek, Vincent Méjean, J Pommier, G. Giordano, J.-p. Dos Santos, Richard HaserAbstract:The periplasmic trimethylamine N-oxide (TMAO) Reductase from the marine bacteria Shewanella massilia is involved in a respiratory chain, having trimethylamine N-oxide as terminal electron acceptor. This molybdoenzyme belongs to the dimethyl sulfoxide (DMSO) Reductase family, but has a different substrate specificity than its homologous enzyme. While the DMSO Reductases reduce a broad spectra of organic S-oxide and N-oxide compounds, TMAO Reductase from Shewanella massilia reduces only TMAO as the natural compound. The crystal structure was solved by molecular replacement with the coordinates of the DMSO Reductase from Rhodobacter sphaeroides. The overall fold of the protein structure is essentially the same as the DMSO Reductase structures, organized into four domains. The molybdenum coordination sphere is closest to that described in the DMSO Reductase of Rhodobacter capsulatus. The structural differences found in the protein environment of the active site could be related to the differences in substrate specificity of these enzymes. In close vicinity of the molybdenum ion a tyrosine residue is missing in the TMAO Reductase, leaving a greater space accessible to the solvent. This tyrosine residue has contacts to the oxo groups in the DMSO Reductase structures. The arrangement and number of charged residues lining the inner surface of the funnel-like entrance to the active site, is different in the TMAO Reductase than in the DMSO Reductases from Rhodobacter species. Furthermore a surface loop at the top of the active-site funnel, for which no density was present in the DMSO Reductase structures, is well defined in the oxidized form of the TMAO Reductase structure, and is located on the border of the funnel-like entrance of the active center.
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Crystal structure of oxidized trimethylamine N-oxide Reductase from Shewanella massilia at 2.5 A resolution.
Journal of Molecular Biology, 1998Co-Authors: Mirjam Czjzek, Vincent Méjean, J Pommier, Jp Dossantos, G. Giordano, Richard HaserAbstract:The periplasmic trimethylamine N-oxide (TMAO) Reductase from the marine bacteria Shewanella massilia is involved in a respiratory chain, having trimethylamine N-oxide as terminal electron acceptor. This molybdoenzyme belongs to the dimethyl sulfoxide (DMSO) Reductase family, but has a different substrate specificity than its homologous enzyme. While the DMSO Reductases reduce a broad spectra of organic S-oxide and N-oxide compounds, TMAO Reductase from Shewanella massilia reduces only TMAO as the natural compound. The crystal structure was solved by molecular replacement with the coordinates of the DMSO Reductase from Rhodobacter sphaeroides. The overall fold of the protein structure is essentially the same as the DMSO Reductase structures, organized into four domains. The molybdenum coordination sphere is closest to that described in the DMSO Reductase of Rhodobacter capsulatus. The structural differences found in the protein environment of the active site could be related to the differences in substrate specificity of these enzymes. In close vicinity of the molybdenum ion a tyrosine residue is missing in the TMAO Reductase, leaving a greater space accessible to the solvent. This tyrosine residue has contacts to the oxo groups in the DMSO Reductase structures. The arrangement and number of charged residues lining the inner surface of the funnel-like entrance to the active site, is different in the TMAO Reductase than in the DMSO Reductases from Rhodobacter species. Furthermore a surface loop at the top of the active-site funnel, for which no density was present in the DMSO Reductase structures, is well defined in the oxidized form of the TMAO Reductase structure, and is located on the border of the funnel-like entrance of the active center.The periplasmic trimethylamine N-oxide (TMAO) Reductase from the marine bacteria Shewanella massilia is involved in a respiratory chain, having trimethylamine N-oxide as terminal electron acceptor. This molybdoenzyme belongs to the dimethyl sulfoxide (DMSO) Reductase family, but has a different substrate specificity than its homologous enzyme. While the DMSO Reductases reduce a broad spectra of organic S-oxide and N-oxide compounds, TMAO Reductase from Shewanella massilia reduces only TMAO as the natural compound. The crystal structure was solved by molecular replacement with the coordinates of the DMSO Reductase from Rhodobacter sphaeroides. The overall fold of the protein structure is essentially the same as the DMSO Reductase structures, organized into four domains. The molybdenum coordination sphere is closest to that described in the DMSO Reductase of Rhodobacter capsulatus. The structural differences found in the protein environment of the active site could be related to the differences in substrate specificity of these enzymes. In close vicinity of the molybdenum ion a tyrosine residue is missing in the TMAO Reductase, leaving a greater space accessible to the solvent. This tyrosine residue has contacts to the oxo groups in the DMSO Reductase structures. The arrangement and number of charged residues lining the inner surface of the funnel-like entrance to the active site, is different in the TMAO Reductase than in the DMSO Reductases from Rhodobacter species. Furthermore a surface loop at the top of the active-site funnel, for which no density was present in the DMSO Reductase structures, is well defined in the oxidized form of the TMAO Reductase structure, and is located on the border of the funnel-like entrance of the active center.
Wilfred R. Hagen - One of the best experts on this subject based on the ideXlab platform.
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The dissimilatory sulfite Reductase from Desulfosarcina variabilis is a desulforubidin containing uncoupled metalated sirohemes and S = 9/2 iron-sulfur clusters
Biochemistry, 1993Co-Authors: Alexander F. Arendsen, Ronnie B. G. Wolbert, Marc F J M Verhagen, Antonio J Pierik, Alfons J M Stams, Mike S. M. Jetten, Wilfred R. HagenAbstract:The active site of Escherichia coli NADPH-sulfite Reductase has previously been modeled as a siroheme with its iron bridged to a nearby iron-sulfur cubane, resulting in antiferromagnetic exchange coupling between all iron atoms. The model has been suggested to hold also for other sulfite Reductases and nitrite Reductases. We have recently challenged the generality of the model with the finding that the EPR of Fe/S in dissimilatory sulfite Reductase (desulfoviridin) from Desulfovibrio vulgaris indicates that an S=9/2 system is not subject to coupling. Siroheme in desulfoviridin is to a large extent demetalated, and therefore coupling is physically impossible. We have now studied examples from a second class of dissimilatory sulfite Reductases, desulforubidins, which have their siroporphyrins fully metalated
