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)

Through the use of specific immunoadsorbent columns, it is shown that Escherichia coli aspartokinase I-homoserine dehydrogenase I, aspartokinase II-homoserine dehydrogenase II, aspartokinase III, and homoserine kinase, enzymes involved in the same complex biosynthetic pathway, share antigenic determinants. This raises the question of a common origin for the four cibtenoirart kinases. (Aspartate kinase or ATP:L aspartate 4-phosphotransferase, EC 2.7.2.4; homoserine dehydrogenase or Lhomoserine:NADP oxidoreductase, EC 1.1.1.3; homoserine kinase or ATP:L-homoserine O-phosphotransferase, EC 2.7.1.39.)
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PMID:Evolution of biosynthetic pathways: immunological approach. 4 55

The activities of glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate: NADP oxidoreductase, G6PD), 6-phosphogluconate dehydrogenase (6-phospho-d-gluconate: NADP oxidoreductase, 6PGD), hexokinase (ATP:D-hexose 6-phosphotransferase, HK), lactic dehydrogeanse (L-lactate: NAD oxidoreductase, LDH) and aspirate aminotransferase (L-aspartate: 2-oxoglutarate aminotransferase, Asp.T) were determined in red blood cells of 11 healthy individuals. The determinations were carried out on samples drawn every 4 h over a 24 h period. The activities of G6PD, 6PGD, LDH and Asp.T exhibited a semi-circadian rhythm, namely, two peaks of activity during 24 h while HK activity demonstrated a true circadian rhythm. In addition a polymorphism of the G6PD and LDH activity patterns was observed. The implications of a biological clock in enucleated cells are discussed.
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PMID:The diurnal rhythm of enzymes in human red cells. 94 47

The mouse LA9 HQN-R11 cytochrome b mutant, in which the glycine residue at position 231 is replaced by aspartic acid, has increased resistance to all inhibitors of the Qn redox center. It is shown here that this single amino acid alteration has multiple and unexpectedly diverse effects upon the mitochondrial protonmotive bc1 complex. (1) The specific activities of both succinate- and ubiquinol-cytochrome c oxidoreductases in isolated mitochondria are reduced by approximately 65% in the mutant. The parallel reductions in both oxidoreductase activities are not compatible with simple Q pool kinetics for mitochondrial electron transport. (2) There is also a reduction in the relative concentration of cytochrome b in the mutant when calculated on the basis of mitochondrial protein; this decrease does not account for more than a small portion of the reduced catalytic fluxes. (3) The increased antimycin resistance of the mutant is lost upon solubilization by the detergent dodecyl maltoside of the bc1 complex from mitochondria. (4) In pre-steady-state assays of cytochrome b reduction by quinol, the mutant shows a reduced extent of reduction. It was observed in other experiments that there was less oxidant-induced extrareduction of cytochrome b in the mutant. These results could arise from a lowering of the midpoint potentials of both the cytochrome b-562 and cytochrome b-566 heme groups. Alternatively, these effects may reflect changes at the Qp and Qn quinone/quinol binding sites. (5) An unexplained observation for the mutant is the increased rate of cytochrome c1 reduction in the presence of myxothiazol. (6) These functional alterations in the LA9 HQN-R11 mutant are not accompanied by detectable changes in the spectral properties of the cytochrome b or c1 heme groups.
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PMID:Glycine-231 residue of the mouse mitochondrial protonmotive cytochrome b: mutation to aspartic acid deranges electron transport. 217 39

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

Several spontaneous mutants of the photosynthetic bacterium Rhodobacter capsulatus resistant to myxothiazol, stigmatellin and mucidin--inhibitors of the ubiquinol: cytochrome c oxidoreductase (cyt bc1 complex)--were isolated. They were grouped into eight different classes based on their genetic location, growth properties and inhibitor cross-resistance. The petABC (fbcFBC) cluster that encodes the structural genes for the Rieske FeS protein, cyt b and cyt c1 subunits of the cyt bc1 complex was cloned out of the representative isolates and the molecular basis of inhibitor-resistance was determined by DNA sequencing. These data indicated that while one group of mutations was located outside the petABC(fbcFBC) cluster, the remainder were single base pair changes in codons corresponding to phylogenetically conserved amino acid residues of cyt b. Of these substitutions, F144S conferred resistance to myxothiazol, T163A and V333A to stigmatellin, L106P and G152S to myxothiazol + mucidin and M140I and F144L to myxothiazol + stigmatellin. In addition, a mutation (aer126) which specifically impairs the quinol oxidase (Qz) activity of the cyt bc1 complex of a non-photosynthetic mutant (R126) was identified to be a glycine to an aspartic acid replacement at position 158 of cyt b. Six of these mutations were found between amino acid residues 140 and 163, in a region linking the putative third and fourth transmembrane helices of cyt b. The non-random clustering of several inhibitor-resistance mutations around the non-functional aer126 mutation suggests that this region may be involved in the formation of the Qz inhibitor binding/quinol oxidation domain(s) of the cyt bc1 complex. Of the two remaining mutations, the V333A replacement conferred resistance to stigmatellin exclusively and was located in another region toward the C terminus of cyt b. The L106P substitution, on the other hand, was situated in the transmembrane helix II that carries two conserved histidine residues (positions 97 and 111 in R. capsulatus) considered to be the axial ligands for the heme groups of cyt b. The structural and functional roles of the amino acid residues involved in the acquisition of Qz inhibitor resistance are discussed in terms of the primary structure of cyt b and in relation to the natural inhibitor-resistance of various phylogenetically related cyt bc/bf complexes.
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PMID:Mutations conferring resistance to quinol oxidation (Qz) inhibitors of the cyt bc1 complex of Rhodobacter capsulatus. 255 59

Amino acid changes in the enzyme l-histidinol dehydrogenase (l-histidinol-NAD oxidoreductase, EC 1.1.1.23) have been determined between the wild-type Neurospora crassa and two temperature-sensitive mutants. Comparison was made between amino acid analyses of peptides of differing electrophoretic and chromatographic mobilities resulting from tryptic and chymotryptic digestion of protein from wild-type and mutant K26, and wild-type and mutant K445 strains, respectively. The analyses demonstrate the substitution of aspartic acid for alanine in mutant K26, and leucine for histidine in mutant K445. The effects of the resulting changes in polarity and charge are discussed in relation to the catalytic functioning of the proteins.
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PMID:Amino acid substitutions in mutant forms of histidinol dehydrogenase from Neurospora crassa. 605 36

The preparation procedure for Spirulina ferredoxin-NADP+ reductase (ferredoxin: NADP+ oxidoreductase, EC 1.18.1.2, FNR) was improved by adding protease inhibitors, phenylmethylsulfonylfluoride (PMSF) and EDTA, through the whole process of preparation and by introducing an affinity chromatography step on Blue Sepharose CL-6B. The addition of the inhibitors largely prevented the formation of the minor component (FNR I), and the affinity gel chromatography simplified the preparation process, shortening the exposure period of FNR to proteolysis. However, complete removal of the heterogeneity of FNR found at the amino (N)-terminal region was not achieved even by applying the new method. The affinity chromatography on the Blue Sepharose gel was also effective in purifying spinach FNR. The affinity of this gel for Spirulina FNR was compared with that for the enzyme derived from spinach leaves. The spinach enzyme had a higher affinity than the Spirulina one. Both enzymes showed the highest affinities to Blue Sepharose at 20--30 mM NaCl concentration. The N-terminal sequence analysis revealed that there was 4 forms, which were probably modifications produced by exopeptidase action during the preparation, or even in the living cells. The longest component gave the N-terminal sequence Ala-Lys-Thr-Asp-Ile-Pro-Val-Asn-Ile-Tyr-. The others lacked amino acids successively one by one from the N-terminus. In contrast, the carboxyl(C)-terminal residues of all 4 FNR forms were tyrosine. The probable C-terminal sequence was predicted to be -Trp-His-Val-Gln-Thr-Tyr based on a study of a cyanogen bromide peptide.
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PMID:Spirulina ferredoxin-NADP+ reductase. Further characterization with an improved preparation. 641 47

6-Phosphogluconate dehydrogenase (6-phospho-D-gluconate: NADP+ 2-oxidoreductase(decarboxylating), EC 1.1.1.44) from Candida utilis is inhibited by reaction with pyridoxal 5'-phosphate. The aldehydic group of this compound forms a Schiff base with the epsilon-amino group of a lysine residue: reduction of this enamine with tritiated borohydride can label this amino acid. Two tryptic peptides, TS2 and TS3, have been isolated from the labelled protein and found to have the following amino acid sequences: TS2: Ile-Leu-Asx-Glx-Ala-Gly-Gly-Lys(P-Pxy)-Gly-Glx-Thr-Lys TS3: Thr-Val-Ser-Lys(P-Pxy)-Val-Asp-His-Phe-Ile-(Glx,Asx,Glx)-Ala-Lys where Lys(P-Pxy) indicates the modified lysine residue. The similarities between the amino acid sequences around the pyridoxal phosphate binding lysines of 38 peptides, obtained from enzymes which have pyridoxal phosphate as cofactor or inhibitor, are discussed and a prediction is made on the presence of reverse turns in these peptides.
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PMID:Amino acid sequence around the pyridoxal 5'-phosphate binding sites of 6-phosphogluconate dehydrogenase. 719 16

Site-directed mutagenesis of the acidic clusters 207Asp-Asp-Asp209 and 213Glu-Glu-Asp215 of NADPH-cytochrome P450 oxidoreductase demonstrates that both cytochrome c and cytochrome P450 interact with this region; however, the sites and mechanisms of interaction of the two substrates are clearly distinct. Substitutions in the first acidic cluster did not affect cytochrome c or ferricyanide reductase activity, but substitution of asparagine for aspartate at position 208 reduced cytochrome P450-dependent benzphetamine N-demethylase activity by 63% with no effect on KP450m or KNADPHm. Substitutions in the second acidic cluster affected cytochrome c reduction but not benzphetamine N-demethylase or ferricyanide reductase activity. The E213Q enzyme exhibited a 59% reduction in cytochrome c reductase activity and a 47% reduction in KCyt cm under standard conditions (x0.27 M potassium phosphate, pH 7.7), as well as a decreased KCyt cm at every ionic strength and a shift of the salt dependence of cytochrome c reductase activity toward lower ionic strengths. The E214Q substitution did not affect cytochrome c reductase activity under standard conditions, but shifted the salt dependence of cytochrome c reductase activity toward higher ionic strengths. Measurements of the effect of ionic strength on steady-state kinetic properties indicated that increasing ionic strength destabilized the reductase-cytochrome c3+ ground state and reductase-cytochrome c transition state complexes for the wild-type, E213Q, and E214Q enzymes, suggesting the presence of electrostatic interactions involving Glu213 and Glu214 as well as additional residues outside this region. The ionic strength dependence of kcat/KCyt cm for the wild-type and E214Q enzymes is consistent with the presence of charge-pairing interactions in the transition state and removal of a weak ionic interaction in the reductase-cytochrome c transition-state complex by the E214Q substitution. The ionic strength dependence of the E213Q enzyme, however, is not consistent with a simple electrostatic model. Effects of ionic strength on kinetic properties of E213Q suggest that substitution of glutamine stabilizes the reductase-cytochrome c3+ ground-state complex, leading to a net increase in activation energy and decrease in kcat. Glu213 is also involved in a repulsive interaction with cytochrome c3+. Cytochrome c2+ Ki for the wild-type enzyme was 82.4 microM at 118 mM ionic strength and 10.8 microM at 749 mM ionic strength; similar values were observed for the E214Q enzyme. Cytochrome c Ki for the E213Q enzyme was 17.6 microM at 118 mM and 15.7 microM at 749 mM ionic strength, consistent with removal of an electrostatic repulsion between the reductase and cytochrome c2+.
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PMID:Role of acidic residues in the interaction of NADPH-cytochrome P450 oxidoreductase with cytochrome P450 and cytochrome c. 749 4

NAD(P)H: quinone-acceptor oxidoreductase (EC 1.6.99.2), also referred to as DT-diaphorase, is a flavoprotein that catalyzes the two-electron reduction of quinones and quinonoid compounds to hydroquinones, using either NADH or NADPH as the electron donor. Using an Escherichia coli expression system developed previously, we prepared three mutants of the rat liver quinone reductase. These mutants are Lys-113-His (K113H), Lys-113-Asp (K113D), and Lys-113-Ala (K113A). While the mutant K113H was readily purified using the same procedure as for the purification of the wild-type quinone reductase and found to have an activity similar to that of the wild-type enzyme, K113D and K113A were purified only in very small quantities, mainly in the form of apoprotein, and had very low activities. The results suggest that a positively charged amino acid at this position is important for the binding of the flavin adenine dinucleotide (FAD) prosthetic group. Flavin spectral studies of 6-mercapto-FAD-reconstituted mutants revealed that mutation at Lys-113 affects the protein environment around position-6 of the isoalloxazine ring.
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PMID:A site-directed mutagenesis study at Lys-113 of NAD(P)H:quinone-acceptor oxidoreductase: an involvement of Lys-113 in the binding of the flavin adenine dinucleotide prosthetic group. 763 39


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