Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q8NEX9 (reductase)
 26,410 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human erythrocytes from healthy male donors were fractionated with respect to in vivo age by simple centrifugation in order to characterize changes in the functional integrity of the membrane during the life-span of the cell. The three enzymes, Na/K-ATPase, glyceraldehyde-3-phosphate dehydrogenase and NADH-ferricyanide reductase, were found not to change with age, but significant age-dependent decreases were observed in the cases of acetylcholinesterase, phosphoglycerate kinase, purine nucleoside phosphorylase, adenylate kinase, Mg-ATPase and alkaline phosphatase. The possibility that these changes were attributable to mechanisms other than age-related inactivation, such as reticulocyte contamination, differential resealing and crypticity, was investigated. Only the decrease in acetylcholinesterase could be explained wholly in terms of reticulocyte contamination. A decrease in membrane integrity on ageing was observed, which accounted for approximately half the change in alkaline phosphatase and may have contributed to the other enzyme activity changes. This membrane integrity effect masked a real decrease in the highly cryptic NADH-ferricyanide reductase, this decrease being apparent only after total disaggregation of the membrane with nonionic surfactant.
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PMID:Changes in the activities of some membrane-associated enzymes during in vivo ageing of the normal human erythrocyte. 14 40

The amino acid sequence of the multifunctional fatty-acid synthase has been examined to investigate the exact location of the seven functional domains. Good agreement in predicting the location of interdomain boundaries was obtained using three independent methods. First, the sites of limited proteolytic attack that give rise to relatively stable, large polypeptide fragments were identified; cryptic sites for protease attack at the subunit interface were unmasked by first dissociating the dimer into its component subunits. Second, polypeptide regions exhibiting higher-than-average rates of non-conservative mutation were identified. Third, the sizes of putative functional domains were compared with those of related monofunctional proteins that exhibit similar primary or secondary structure. Residues 1-406 were assigned to the oxoacyl synthase, residues 430-802 to the malonyl/acetyl transferase, residues 1630-1850 to the enoyl reductase, residues 1870-2100 to the oxyreductase, residues 2114-2190 to the acyl-carrier protein and residues 2200-2505 to the thioesterase. The 47-kDa transferase and 8-kDa acyl-carrier-protein domains, which are situated at opposite ends of the multifunctional subunit, were nevertheless isolated from tryptic digests as a non-covalently associated complex. Furthermore, a centrally located domain encompassing residues 1160-1545 was isolated as a nicked dimer. These findings, indicating that interactions between the head-to-tail juxtaposed subunits occur in both the polar and equatorial regions, are consistent with previously derived electron-micrograph images that show subunit contacts in these areas. The data permit refinement of the model for the fatty-acid synthase dimer and suggest that the malonyl/acetyl transferase and oxoacyl synthase of one subunit cooperate with the reductases, acyl carrier protein and thioesterase of the companion subunit in the formation of a center for fatty-acid synthesis.
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PMID:Structural organization of the multifunctional animal fatty-acid synthase. 205 Jan 37

Mercuric reductase activity determined by the Thiobacillus ferrooxidans merA gene (cloned and expressed constitutively in Escherichia coli) was measured by volatilization of 203Hg2+. (The absence of a merR regulatory gene in the cloned Thiobacillus mer determinant provides a basis for the constitutive synthesis of this system.) In the absence of the Thiobacillus merC transport gene, the mercury volatilization activity was cryptic and was not seen with whole cells but only with sonication-disrupted cells. The Thiobacillus merC transport function was compared with transport via the merT-merP system of plasmid pDU1358. Both systems, cloned and expressed in E. coli, governed enhanced uptake of 203Hg2+ in a temperature- and concentration-dependent fashion. Uptake via MerT-MerP was greater and conferred greater hypersensitivity to Hg2+ than did uptake with MerC. Mercury uptake was inhibited by N-ethylmaleimide but not by EDTA. Ag+ salts inhibited mercury uptake by the MerT-MerP system but did not inhibit uptake via MerC. Radioactive mercury accumulated by the MerT-MerP and by the MerC systems was exchangeable with nonradioactive Hg2+.
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PMID:Constitutive synthesis of a transport function encoded by the Thiobacillus ferrooxidans merC gene cloned in Escherichia coli. 218 29

The mocC gene encoded by the octopine/mannityl opine-type Ti plasmid pTi15955 is related at the nucleotide sequence level to mas1' encoded by the T region of this plasmid. While Mas1 is required for the synthesis of mannopine (MOP) by crown gall tumor cells, MocC is essential for the utilization of MOP by Agrobacterium spp. A cosmid clone of pTi15955, pYDH208, encodes mocC and confers the utilization of MOP on strain NT1 and on strain UIA5, a derivative of NT1 lacking the 450-kb cryptic plasmid pAtC58. NT1 or UIA5 harboring pYDH208 with an insertion mutation in mocC failed to utilize MOP as the sole carbon source. Plasmid pSa-C, which encodes only mocC, complemented this mutation in both strains. This plasmid also was sufficient to confer utilization of MOP on NT1 but not on UIA5. Computer analysis showed that MocC is related at the amino acid sequence level to members of the short-chain alcohol dehydrogenase family of oxidoreductases. Lysates prepared from Escherichia coli cells expressing mocC contained an enzymatic activity that oxidizes MOP to deoxyfructosyl glutamine (santhopine [SOP]) in the presence of NAD+. The reaction catalyzed by the MOP oxidoreductase is reversible; in the presence of NADH, the enzyme reduced SOP to MOP. The apparent Km values of the enzyme for MOP and SOP were 6.3 and 1.2 mM, respectively. Among analogs of MOP tested, only N-1-(1-deoxy-D-lyxityl)-L-glutamine and N-1-(1-deoxy-D-mannityl)-L-asparagine served as substrates for MOP oxidoreductase. These results indicate that mocC encodes an oxidoreductase that, as an oxidase, is essential for the catabolism of MOP. The reductase activity of this enzyme is precisely the reaction ascribed to its T-region-encoded homolog, Mas1, which is responsible for biosynthesis of mannopine in crown gall tumors.
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PMID:A Ti plasmid-encoded enzyme required for degradation of mannopine is functionally homologous to the T-region-encoded enzyme required for synthesis of this opine in crown gall tumors. 865 10

Enterobacteriaceae contain genes for three separate ribonucleotide reductases: nrdAB code for a class Ia enzyme, active during aerobiosis, nrdDG for a class III enzyme, active during anaerobiosis, and nrdEF for a cryptic class Ib enzyme. The NrdEF enzyme provides the active reductase in other, widely different bacteria. Here, we describe the allosteric regulation of the Salmonella typhimurium NrdEF enzyme. It consists of two tightly bound homodimeric proteins, R1E and R2F. Nucleoside triphosphates (ATP, dATP, dGTP, and dTTP) regulate the substrate specificity by binding to a single site of the R1E protein (one nucleotide per polypeptide). Regulation is similar to that of the NrdAB enzyme, with one major exception: dATP stimulates reduction of CDP (and UDP) under conditions when dATP strongly inhibits all activity of the NrdAB enzyme. The nrdA-coded R1 protein contains a second binding site for dATP (and ATP) that controls general enzyme activity. All known R1E proteins lack the 50 N-terminal amino acids of R1, and we propose that the activity site is located in this area of the protein. The more sophisticated regulation of NrdAB enzymes of eukaryotes provides protection against the possibly harmful overproduction of dNTPs.
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PMID:Allosteric regulation of the third ribonucleotide reductase (NrdEF enzyme) from enterobacteriaceae. 890 Jan 30

The 569,750 base pair sequence corresponding to the 28.0-40.1 min region on the genetic map of Escherichia coli K-12 (W3110) was determined. This region includes the replication terminus region and contained at least 549 potential open reading frames. Among them, 160 (29%) were previously reported, 174 (32%) were homologous to other known genes, 102 (18%) were identical or similar to hypothetical genes registered in databases, and the remaining 113 (21%) did not show a significant similarity to any other gene. Of interest was the finding of a large number of genes and gene clusters in and near the replication termination region which had been thought to be genetically silent. Those included a cluster of genes for fatty acid beta-oxidation, the third copy of the pot (spermidine/putrescine transport system) gene cluster, the second dpp (dipeptide transport system) operon, the second dsm (anaerobic dimethyl sulfoxide reductase) operon, a cluster of fim (fimbrial) genes and a DNA helicase-like gene with a high molecular weight. In addition, we found the dnaC- and dnaT-like genes in the cryptic prophage, Rac, and a number of genes originated probably from plasmids.
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PMID:A 570-kb DNA sequence of the Escherichia coli K-12 genome corresponding to the 28.0-40.1 min region on the linkage map. 909 39

A Pasteurella haemolytica A1 gene was identified from a recombinant library clone that expressed hemolysis in host Escherichia coli cells. The gene, designated fnrP, had sequence identity to E. coli fnr, a global transcriptional regulator of genes required for conversion to anaerobic growth. FnrP complemented anaerobic deficiencies of a fnr-null mutant strain of E. coli and increased expression of the Fnr-dependent, anaerobic terminal reductase gene, frdA. FnrP was purified, identified by immunoblotting, and shown to be nonhemolytic. When FnrP was expressed in E. coli DeltasheA, a null mutant of the cryptic hemolysin SheA, the transformants were nonhemolytic, indicating that FnrP activates this silent hemolysin.
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PMID:Cloning and characterization of the gene encoding Pasteurella haemolytica FnrP, a regulator of the Escherichia coli silent hemolysin sheA. 1036 64

Escherichia coli has two aerobic ribonucleotide reductases encoded by the nrdAB and nrdHIEF operons. While NrdAB is active during aerobiosis, NrdEF is considered a cryptic enzyme with no obvious function. Here, we present evidence that nrdHIEF expression might be important under certain circumstances. Basal transcript levels were dramatically enhanced (25-75-fold), depending on the growth-phase and the growth-medium composition. Likewise, a large increase of >100-fold in nrdHIEF mRNA was observed in bacteria lacking Trx1 and Grx1, the two main NrdAB reductants. Moreover, nrdHIEF expression was triggered in response to oxidative stress, particularly in mutants missing hydroperoxidase I and alkyl-hydroperoxide reductase activities (69.7-fold) and in cells treated with oxidants (up to 23.4-fold over the enhanced transcript level possessed by cells grown on minimal medium). The mechanism(s) that triggers nrdHIEF expression remains unknown, but our findings exclude putative global regulators like RpoS, Fis, cAMP, OxyR, SoxR/S, or RecA. What we have learned about nrdHIEF expression indicates strong differences between its regulation and that of the nrdAB operon and of genes coding for components of both thioredoxin/glutaredoxin pathways. We propose that E. coli might optimize the responses to different stimuli by co-evolving the expression levels for its multiple reductases and electron donors.
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PMID:Expression analysis of the nrdHIEF operon from Escherichia coli. Conditions that trigger the transcript level in vivo. 1127 73

Rhodococcus erythropolis KA2-5-1 can desulfurize dibenzothiophene (DBT) into 2-hydroxybiphenyl. A cryptic plasmid, pRC4, which was derived from R. rhodochrous IFO3338, was combined with an Escherichia coli vector to construct an E. coli-Rhodococcus shuttle vector. The complete nucleotide sequence of 2582-bp pRC4 was analyzed. Based on the characteristics of its putative replication genes, pRC4 was assigned to the family of pAL5000-related replicons. The desulfurization gene cluster, dszABC, and the related reductase gene, dszD, cloned from KA2-5-1, were reintroduced into KA2-5-1 and efficiently expressed. The DBT desulfurization ability of the transformant carrying two dszABC clusters and one dszD on the vector was about 4-fold higher than that of the parent strain, and the transformant also showed improved desulfurization activity for light gas oil (LGO). Sulfur components in LGO before and after the reaction were analyzed with gas chromatography-atomic emission detection.
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PMID:Improvement of desulfurization activity in Rhodococcus erythropolis KA2-5-1 by genetic engineering. 1130 54

Aldo-keto-reductase 1B7/mouse vas deferens protein (AKR1B7/MVDP) is expressed in rodent steroidogenic glands and in the mouse vas deferens. In steroidogenic organs, AKR1B7/MVDP scavenges isocaproaldehyde produced from the cholesterol side-chain cleavage reaction. Akr1b7/mvdp is responsive to ACTH in adrenals and to androgens in vas deferens. Using transgenic mice, we previously delimited the regulatory DNA sequences necessary for expression in both organs and identified by cell transfections, a cryptic steroidogenic factor-1 (SF-1) response element (SFRE) at -102 that overlaps a proximal androgen-responsive element. To address its in vivo functions in adrenals, we devised a transgenic mouse study using wild-type and mutant akr1b7 promoters driving the chloramphenol acetyltransferase reporter gene. Adrenal expression in adults was impaired in all lines mutant for -102 SFRE. This effect is linked to impaired SF-1 binding and not to impaired androgen receptor binding, because akr1b7 expression is not affected in adrenals of androgen receptor-defective Tfm mice. Triphasic developmental patterns of both AKR1B7 and wild-type transgene expression paralleled changes in SF-1 levels/binding activity; expression was maximal in late embryos, minimal in 6- to 15-d-old neonates, and thereafter progressively restored. Differences in developmental expression between wild-type and mutant transgenes revealed that requirement for the -102 SFRE appears stage specific, as its integrity is an absolute prerequisite for reinduction of gene expression after postnatal d 15. Further, mutation of this site did not affect transgene responsiveness to ACTH. These findings demonstrate a new function for SFRE in vivo, via influencing promoter sensibility to postnatal changes of SF-1 contents, in controlling promoter strength in adults without affecting adrenal targeting, hormonal control, or early gene expression.
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PMID:Steroidogenic factor-1 controls the aldose reductase akr1b7 gene promoter in transgenic mice through an atypical binding site. 1269 20


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