Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

NAD(P)H: FMN oxidoreductase (flavin reductase) couples in vitro to bacterial luciferase. This reductase, which is also postulated to supply reduced flavin mononucleotide in vivo as a substrate for the bioluminescent reaction, has been partially purified and characterized from two species of luminous bacterial. From Photobacterium fischeri the enzyme has a M. W. determined by Sephadex gel filtration, of 43,000 and may have a subunit structure. The turnover number at 20 degrees C, based on a purity estimate of 20 percent, is 1.7 times 10-4 moles of NADH oxidized per min per mole of reductase. The reductase isolated from Beneckea harveyi has an apparent molecular weight of 23,000; its purity was too low to permit estimation of specific activity. Using a spectrophotometric assay at 340 nm with the P. fischeri reductase, both NADH (Km, 8 times 10-5 M) and NADPH (Km, 4 times 10-4 M) were enzymatically oxidized, the Vmax with NADH being approximately twice that of NADPH. Of the flavins tested in this assay, only FMN (Km, 7.3 times 10-5 M) and FAD (Km, 1.4 times 10-4 M) were effective, FMN having a Vmax three times that of FAD. In the coupled assay, i.e., measuring the bioluminescence intensity of the reaction with added luciferase, the optimum FMN concentration was nearly 100 times less than in the spectrophotometric assay. The studies reported suggest the existence of a functional reductase-luciferase complex.
Mol Cell Biochem 1975 Jan 31
PMID:Flavin mononucleotide reductase of luminous bacteria. 4 4

From previous work (Guiard, B., Groudinsky, O. and Lederer, F. (1974) Proc. Natl. Acad. Sci. U.S. 71, 2539-2543) it is now clear that the overall secondary and tertiary structure of cytochrome b2 core is very similar to that of cytochrome b5. We present here a direct comparison of circular dichroism spectra and low-temperature absorption spectra which bring further evidence about this structural similarity. Cytochrome b2 core reacts only sluggishly with cytochrome b5 reductase, showing a lack of correspondence with the reductase binding area in cytochrome b5. On the other hand, literature data indicate similar electron transfer rates between cytochrome c on one hand, cytochrome b5 and cytochrome b2 core on the other hand. A structural inspection of cytochrome b2 core suggests that the mouth of the heme crevice in the latter is the most likely region for interaction with cytochrome c, with perhaps ionic bonds slightly different from those proposed by Salemme (Salemme, F.R. (1976) J. Mol. Biol. 102, 563--568) for the cytochrome c-cytochrome b5 interaction. In view of this partial surface similarity, the lack of immunological cross-reactivity between the two hemoprotein cores is attributed to their close similarity with the cytochrome b5 of the antibody-producing rabbit.
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PMID:Surface differences and similarities in two homologous proteins. Cytochrome b5 and cytochrome b2 core. 10 Dec 51

Measurement of the effect of drugs on the in vivo rates of synthesis of rabbit liver organelle bound proteins were measured following individual treatments with the inducers phenobarbital, 3-methylcholanthrene and PCB (a mixture of polychlorinated biphenyls) and the inhibitors, cycloheximide, aflatoxin B1, chloramphenicol and actinomycin D. Following their isolation from a homogenate containing the combined livers of 14C-leucine injected experimental animals and 3H-leucine injected control animals, purified fractions of the following proteins were prepared: microsomal cytochrome b5, cytochrome P-450, NADH-cytochrome b5 reductase, NADPH-cytochrome P-450 reductase and proteolipids, outer mitochondrial membrane cytochrome b5, NADH-cytochrome b5 reductase and proteolipids, inner mitochondrial membrane cytochrome c, NADH dehydrogenase and proteolipids, intermitochondrial membrane cytochrome b5 and circulating serum albumin. The effect of a drug was examined by measuring the 14C/3H ratio of leucine incorporation of each fraction; ratios which differed markedly from a control value of 1 represented actual changes in the relative rates of protein synthesis. Increased rates of synthesis of cytochrome P-450 and its reductase, intermitochondrial membrane cytochrome b5 and all three proteolipid fractions resulted from each inducer treatment. Treatments with 3-methylcholanthrene and PCB also increased the rate of synthesis of cytochrome b5 and its reductase in both the microsome and outer mitochondrial membrane. In addition, the PCB treatment increased the rates of synthesis of cytochrome c and NADH-dehydrogenase. The rates of synthesis of cytochromes, reductases and of circulating serum albumin were inhibited following treatments with cycloheximide, aflatoxin B1 and actinomycin D. Actinomycin D appeared to inhibit the release of newly synthesized albumin into the bloodstream while chloramphenicol treatment appeared to inhibit the incorporation of cytochrome c into the mitochondria. After 20 hours of treatment with inhibitors, the inhibitory effect of actinomycin D and cycloheximide were still apparent while the rates of protein synt;esis in chloramphenicol and aflatoxin B1 treated animals increased to levels above the controls. The incorporation of radioactively labeled leucine into the proteolipids of the microsomal, and the outer and inner mitochondrial membranes were inhibited following the treatment with actinomycin D and stimulated following the treatment with cycloheximide.
Mol Cell Biochem 1979 Dec 14
PMID:Effect of a single dose of inducers and inhibitors on the rate of synthesis of cytochromes and reductases in liver organelles. 11 59

Added free fatty acids inhibit oxidation of glycerol 3-phosphate, succinate and NADH in brown-adipose tissue mitochondria from 10-day-old rats. The most pronounced is the inhibitory effect of glycerol 3-phosphate cytochrome c reductase (GP-cyto. c reductase). Contrary to other reductases, GP-cyto. c reductase activity of freshly isolated mitochondria is already inhibited by the fraction of endogenous free fatty acids. Both added and endogenous free fatty acids inhibition of GP-cyto. c reductase is fully reversible by the removal of free fatty acids by bovine serum albumine treatment. The inhibition of GP-cyto. c reductase is of strictly non-competitive type. The most inhibitory are unsaturated long-chain free fatty acids-oleic and linoleic acid. Results are discussed with regards to the regulatory importance of free fatty acids in brown-adiposetissue during intensive non-shivering thermogenesis.
Mol Cell Biochem 1975 Apr 30
PMID:The regulation of glycerol 3-phosphate oxidase of rate brownadipose tissue mitochondria by long-chain free fatty acids. 16 98

In Saccharomyces cerevisiae, argB and argC define two adjacent and complementing loci, with mutants defective in two consecutive steps of arginine biosynthesis: N-acetylglutamate kinase (AG-kinase) and N-acetylglutamyl-phosphate reductase (AGPreductase). These enzymic activities are readily separated by ammonium sulfate fractionation or Sephadex G-200 chromatography. This suggests that each activity is carried in vivo by a different protein. The synthesis of the two enzymes is coordinately regulated, with an 85-fold difference in specific activities between fully repressed and fully derepressed cells. Missence mutations of the argB locus are defective in AGkinase only. Nonsense mutations in the argB locus are defective in both activities. Missense and nonsense mutations in the argC locus are defective in AGPreductase, with a few alleles also showing a reduced level of AGkinase. These data are best explained by assuming that argB and argC are two genes transcribed as a single messenger from argB to argC. This messenger produces in vivo two distinct proteins corresponding to the argB and argC gene products, either because translation can be initiated at the beginning of both genes, or because a large polypeptide is specifically cut in vivo to yield the gene products of argB and argC.
Mol Gen Genet 1979 Jan 11
PMID:Organization and expression of a two-gene cluster in the arginine biosynthesis of Saccharomyces cerevisiae. 22 May 8

Cytochrome P450 in the mitochondria of the adrenal cortex functions in the monooxygenation reactions for the biosynthesis of various steroid hormones, such as cholesterol side chain cleavage, hydroxylation at 11 beta-position and that at 18-position of the steroid structure. The cytochrome is firmly associated with the mitochondrial membrane and therefore can be isolated only by the aid of ionic or non-ionic detergent. Recently, two cytochromes P450 each catalyzing a specified reaction have been purified to a homogeneous state, that is, P450scc having cholesterol side chain cleavage activity and P45011 beta having 11 beta-hydroxylation activity. The properties of these purified P450's as well as the other components of the monooxygenase system, adrenodoxin and adrenodoxin reductase, are, therefore, summarized and compared to those of P450 in the mitochondrial preparation in situ. Among many findings, both purified cytochromes P450 were revealed to be a low-spin type hemoprotein and their spin states were changed to a high-spin state by being complexed with the corresponding substrate. The binding of a substrate also facilitated the reduction of the cytochrome and appeared to increase the stability of the oxygenated form of cytochrome P450. These effects are important from the point of view that the primary role of the heme of cytochrome P450 is the activation of molecular oxygen. In addition, the results of our detailed kinetic studies on the transfer of electrons from adrenodoxin to cytochrome P450 in the reconstituted system have also been described. Finally, the topology of adrenodoxin and the reductase were shown to be on the inner mitochondrial membrane by a peroxidase-labeled antibody method.
Mol Cell Biochem 1979 Mar 05
PMID:Cytochrome P450 in adrenocortical mitochondria. 22 25

DNA fragments of the R factor R388 which renders E. coli resistant to trimethoprim by inducing a trimethoprim resistant dihydrofolate reductase (Amyes and Smith, 1974) were inserted into plasmids and screened for the expression of the trimethoprim resistance gene. By means of a two step deletion procedure a 1770 bp EcoRI/BamH1 fragment was isolated which conferred drug resistance and which was found to induce the synthesis of the same dihydrofolate reductase as the parental R factor. Gene dosage experiments indicated that the induction was due to the presence of a dihydrofolate reductase structural gene on the 1770 bp fragment. The gene could be assigned to a segment which was less than 1200 bp long. The 1770 bp fragment and a recombinant plasmid consisting of pSF2124 and part of R388 were mapped with several restriction nucleases. The R factor induced enzyme was partially purified from a strain carrying a multicopy recombinant plasmid into which the 1770 bp fragment was inserted and which induced high levels of dihydrofolate reductase. The enzyme was found to be stable at 100 degrees. Some aspects of the synthesis of dihydrofolate reductase are discussed.
Mol Gen Genet 1978 Aug 04
PMID:Isolation of a small DNA fragment carrying the gene for a dihydrofolate reductase from a trimethoprim resistance factor. 36 38

A method for selection of constitutive cysB mutation is described which takes advantage of the resistance of cysteine constitutive mutants to 1,2,4-triazole. Since cysM cysK double mutants are cysteine auxotrophs, by selecting for triazole resistance in cysM strains, mutants arising under this condition also should be constitutive for cysteine biosynthesis. Genetic analysis of mutants isolated by this technique showed that their mutational sites are located in the cysB region. Biochemical assays of cysteine enzymes, sulphite reductase and O-acetylserine sulfhydrylase of the mutants showed the derepressed level of these enzymes and the lack or slight repression by 1-cysteine.
Mol Gen Genet 1978 Oct 24
PMID:Method of isolation of cysteine constitutive mutants of the cysteine regulon in Salmonella typhimurium. 36 63

Diuron-resistance, DIU (Colson et al., 1977), antimycin-resistance, ANA (Michaelis, 1976; Burger et al., 1976), funiculosin-resistance, FUN (Pratje and Michaelis, 1977; Burger et al., 1977) and mucidin-resistance, MUC (Subik et al., 1977) are each coded by a pair of genetic loci on the mit DNA of S. cerevisiae. In the present paper, these respiratiory-competent, drug-resistant loci are localized relative to respiratory-deficient BOX mutants deficient in coenzyme QH2-cytochrome c reductase (Kotylak and Slonimski, 1976, 1977) using deletion and recombination mapping. Three drug-resistant loci possessing distinct mutated allelic forms are distinguished. DIU1 is allelic or closely linked to ANA2, FUN1 and BOX1; DIU2 is allelic or closely linked to ANA1, MUC1 and BOX4/5; MUC2 is allelic to BOX6. The high recombinant frequencies observed between the three loci (13% on the average for 33 various combinations analyzed) suggest the existence of either three genes coding for three distinct polypeptides or of a single gene coding for a single polypeptide but subdivided into three easily separable segments. The resistance of the respiratory-chain observed in vitro in the drug-resistant mutants and the allelism relationships between respiratory-competent, drug-resistant loci and coQH2-cyt c reductase deficient, BOX, loci strongly suggest that each of the three drug-resistant loci codes for a structural gene-product which is essential for the normal coQH2-cyt c reductase activity and is obviously a good candidate for a gene product of the drug-resistant loci mapped in this paper. Polypeptide length modifications of cytochrome b were observed in mutants deficient in the coQH2-cyt c red and localized at the BOX1, BOX4 and BOX6 genetic loci (Claisse et al., 1977, 1978) which are precisely the loci allelic to drug resistant mutants as shown in the present work. Taken together these two sets of data provide a strong evidence in favor of the idea that there exist three non contiguous segments of the mitochondrial DNA sequence which code for a single polypeptide sequence of cytochrome b. In each segment mutations which modify the polypeptide sequence can occur leading to the loss (BOX mutants) or to a modification (drug resistant mutants) of the enzyme activity.
Mol Gen Genet 1979 Jan 02
PMID:Genetic localization of diuron- and mucidin-resistant mutants relative to a group of loci of the mitochondrial DNA controlling coenzyme QH2-cytochrome c reductase in Saccharomyces cerevisiae. 36 93

The biological pathways of ribonucleotide reduction are briefly reviewed. The hypothesis is presented that reduction of ribonucleoside triphosphates to their deoxynucleotide analogs through the mediation of vitamin B12 or a similar corrinoid preceded and was necessary for the subsequent development of a DNA-type genome. There are two known biological systems for ribonucleotide reduction: (1) The ribonucleoside diphosphate reduction system which utilizes a nonheme iron ribonucleotide reductase enzyme, thioredoxin and its reductase, and NADPH. This enzyme complex is found in most bacteria, some higher organisms, and in all animals. (2) The ribonucleoside triphosphate reduction system which utilizes adenosyl cobalamin, ribonucleotide reductase and either thioredoxin or a disulfhydryl compound. The cobalamin-dependent reductase is restricted to a few species of bacteria and blue-gree algae. This system is considered more primitive than the iron reductase one based on their differences in distribution, components, and products.
J Mol Evol 1977 Dec 29
PMID:Ribonucleotide reduction and the possible role of cobalamin in evolution. 59 75


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