Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transcription of the nrdDG operon, which encodes the class III nucleotide reductase, which is only active under anaerobic conditions, was strongly induced after a shift to anaerobiosis. The induction was completely dependent on the transcriptional activator FNR and was independent of the ArcA-ArcB two-component response regulator system. The nrdD transcript start site was mapped to a position immediately downstream of two FNR binding sites. Transcription of the other two nucleotide reductase operons, nrdAB and nrdEF, did not respond to oxygen conditions in a wild-type background, but nrdAB expression was increased in the fnr mutant under anaerobic conditions.
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PMID:FNR-mediated oxygen-responsive regulation of the nrdDG operon of Escherichia coli. 1292 8

In the search for new natural products with anti-oxidant activity, we have combined the cell-free assay based on the scavenging of the stable radical 2,2-diphenyl-1-picrylhydrazyl (DPPH), with a bioassay that detects oxidative mutagens. This bioassay uses a new Escherichia coli tester strain, IC203, specifically sensitive to oxidative stress due to a deficiency in the OxyR function. OxyR is a redox-sensitive transcriptional activator of genes encoding anti-oxidant enzymes such as catalase and peroxiredoxin alkyl hydroperoxide reductase. The positive response observed in E. coli IC203 with several known anti-oxidants, including cysteine, catechol and ascorbic acid, suggested to us the usefulness of the mutagenicity assay for a rapid screening of anti-oxidant compounds. The extract from Penicillium novae-zeelandiae was found to scavenge the DPPH radical. Subsequently, guided by the DPPH-scavenging assay and the oxidative mutagenesis assay, we isolated and identified three compounds in fractions from that active extract: patulin (1). 3-hydroxybenzyl alcohol (2). and gentisyl alcohol (2,5-dihydroxybenzyl alcohol) (3). Of these, gentisyl alcohol showed both DPPH-scavenging activity and oxidative mutagenicity. This compound also gave rise to intracellular formation of superoxide, evaluated by monitoring the oxidation of dihydroethidium, and was able to inhibit mutagenesis induced by the model oxidant t-butyl hydroperoxide (t-BuOOH).
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PMID:Screening for metabolites from Penicillium novae-zeelandiae displaying radical-scavenging activity and oxidative mutagenicity: isolation of gentisyl alcohol. 1294 27

NnrR, a transcriptional activator and member of the CRP/FNR family of regulators, is responsible for controlling the expression of a number of denitrification genes in Rhodobacter sphaeroides 2.4.3. The apparent effector for NnrR is nitric oxide, and in its presence NnrR activates expression of the nirK gene and the nor operon, encoding nitrite reductase and nitric oxide reductase, respectively. Whether nitric oxide directly interacts with NnrR to activate transcription is unknown. Other denitrifiers carry putative orthologs of NnrR. To gain insight into NnrR function, a number of conserved residues were mutagenized. The impact of these changes on NnrR function was assessed by monitoring expression of a nirK-lacZ fusion. In this way a region spanning from Tyr93 to Cys103 that contains residues critical for NnrR activity was identified.
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PMID:Site-directed mutagenesis of NnrR: a transcriptional regulator of nitrite and nitric oxide reductase in Rhodobacter sphaeroides. 1468 Jun 95

We found Nhp6a/b yeast HMG-box chromatin-associated architectural factors and Ssn6 (Cyc8) corepressor to be crucial transcriptional coactivators of FRE2 gene. FRE2 encoding a plasma membrane ferric reductase is induced by the iron-responsive, DNA-binding, transcriptional activator Aft1. We have shown that Nhp6 interacts directly with the Aft1 N-half, including the DNA-binding region, to facilitate Aft1 binding at FRE2 UAS. Ssn6 also interacts directly with the Aft1 N-half and is recruited on FRE2 promoter only in the presence of both Aft1 and Nhp6. This Nhp6/Ssn6 role in Aft1-mediated transcription is FRE2 promoter context specific, and both regulators are required for activation-dependent chromatin remodeling. Our results provide the first in vivo biochemical evidence for nonsequence-specific HMG-box protein-facilitated recruitment of a yeast gene-specific transactivator to its DNA target site and for Nhp6-mediated Ssn6 promoter recruitment. Ssn6 has an explicitly coactivating role on FRE2 promoter only upon induction. Therefore, transcriptional activation in response to iron availability involves multiple protein interactions between the Aft1 iron-responsive DNA-binding factor and global regulators such as Nhp6 and Ssn6.
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PMID:Nhp6 facilitates Aft1 binding and Ssn6 recruitment, both essential for FRE2 transcriptional activation. 1473 28

Although quinoline 2-oxidoreductase (Qor) and 1H-2-oxoquinoline 8-monooxygenase (OxoOR), which catalyse the first two steps of quinoline degradation by Pseudomonas putida 86, and their genes have been investigated in some detail, the genetic organization and regulation of the catabolic pathway are not known yet. A gene cluster involved in quinoline degradation was characterized. Upstream of oxoO encoding the oxygenase component of OxoOR, the gene oxoS coding for a XylS-type protein is located. The DNA region downstream of oxoO comprises potential open reading frames (ORFs) that may code for further catabolic enzymes (an alpha/beta-hydrolase fold protein, and an amidase), and for accessory proteins presumably required for the assembly of metal cofactor containing holoenzymes (XdhC-like protein, MoeC- and MobA-like protein(s), IscS and IscU). The potential iscU gene is followed by the genes qorMSL that encode the structural subunits of Qor. Three potential ORFs (ORFs7-9) are located between qorMSL and oxoR, which codes for the reductase component of OxoOR. ORFs7-9 have counterparts in the cox (CO oxidizing system) and nic (nicotine degradation) gene clusters. Transcription of all these genes and ORFs located downstream of oxoS is induced by quinoline or 1H-2-oxoquinoline. Insertional inactivation of oxoS abolished quinoline-induced transcription. However, weak transcription of ORFs7-9 also occurred independent of quinoline and OxoS. The typical tandem recognition site for a XylS-type transcriptional activator was identified in the putative promoter region of qorM, and archetypal XylS indeed was found to activate synthesis of Qor. Motifs corresponding to single half-sites of a XylS-type binding site are located upstream of oxoO, the xdhC-like gene, and oxoR. Putative quinoline-specific transcriptional start sites were identified for these genes, and for qorM. The gene cluster probably is transcribed from several promoters, resulting in multiple overlapping polycistronic mRNAs.
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PMID:Sequence and transcriptional analysis of a gene cluster of Pseudomonas putida 86 involved in quinoline degradation. 1509 4

Desulfomonile, Desulfitobacterium, and Dehalobacter are anaerobic microbes that can derive energy from the reductive dehalogenation of chlorinated organic compounds, many of which are environmental pollutants. There is very little information about how anaerobic dehalorespiration is regulated. An open reading frame within the Desulfitobacterium dehalogenans chlorophenol reductase (cpr) gene cluster (cprK) was proposed to be a transcriptional regulatory protein (Smidt, H., van Leest, M., van der Oost, J., and deVos, W. M. (2000) J. Bacteriol. 182, 5683-5691). We have cloned, actively overexpressed in Escherichia coli, and purified to homogeneity the D. dehalogenans CprK. The results of electrophoretic mobility shift assays, DNA footprinting studies, and promoter-lac fusion experiments indicate that CprK is a transcriptional activator of the cpr gene cluster. CprK binds 3-chloro-4-hydroxyphenylacetate (CHPA) with high affinity (K(d) = 3.5 mum, determined by isothermal titration calorimetry), which promotes its specific interaction with a DNA sequence (TTAAT-N4-ACTAA) located upstream of the -35 and -10 promoter regions of several cpr genes and activates transcription of these genes. Binding to the upstream "box" sequence increases the affinity of CprK for CHPA by approximately 10-fold (K(d) = 0.4 mum, determined by electrophoretic mobility shift assays). Chlorophenylacetate, which lacks the ortho-hydroxy group, and hydroxyphenylacetate, lacking the chlorine group, do not activate transcription or promote DNA binding, even at millimolar concentrations, at least 1000-fold higher than the K(d) value for CHPA. Lacking metals, CprK is oxygen-sensitive. Oxidation by diamide, which converts thiols to the disulfide, inactivates CprK, and reduction of the oxidized protein by dithiothreitol fully restores DNA binding, indicating that CprK is redox-regulated and is active only when reduced. This is the first reported characterization of a transcriptional regulator of anaerobic dehalorespiration.
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PMID:Regulation of anaerobic dehalorespiration by the transcriptional activator CprK. 1538 94

We have isolated and characterized three adjacent Saccharomyces douglasii genes that share remarkable structural homology (97% amino acid sequence identity) with Saccharomyces cerevisiae ARR1 (ACR1), ARR2 (ACR2) and ARR3 (ACR3) genes involved in arsenical resistance. The ARR2 and ARR3 genes encoding the cytoplasmic arsenate reductase and the plasma membrane arsenite transporter are functionally interchangeable in both yeast species. In contrast, a single copy of S. douglasii ARR1 gene is not sufficient to complement the arsenic hypersensitivity of a S. cerevisiae mutant lacking the transcriptional activator Arr1p. This inability may be related to a deletion of a 35-bp sequence including the putative Yap-binding element in the ARR1 promoter of S. douglasii. Different mechanisms of regulation of ARR1 genes expression may therefore explain the increased tolerance of S. douglasii to arsenic in comparison with S. cerevisiae. The apparent duplication of the ARR gene cluster in the S. douglasii genome may constitute another factor contributing to the observed differences in arsenic sensitivity. Comparison of ARR genes from the genomes of several yeast species indicates that they are located in subtelomeric regions undergoing rapid evolution involving large-scale genomic rearrangements.
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PMID:Arsenical resistance genes in Saccharomyces douglasii and other yeast species undergo rapid evolution involving genomic rearrangements and duplications. 1545 Jan 89

Cryptococcus neoformans is subject to oxidative attack by host immune cells; consequently, oxidant-resistant mechanisms may be important in pathogenesis. Mutations at the OXY2 locus confer decreased laccase and increased sensitivity to hyperbaric oxygen in the background of the oxyl mutation, but, alone, do not confer sensitivity to oxidants. Because metal deficiency can potentiate or ameliorate sensitivity to oxidants, and because the melanin-synthesizing laccase contains copper, we investigated copper acquisition in an oxy2 mutant. We found that its external Cu/Fe reductase activity was lower than that of wild type, and although copper deprivation induced the reductase in the wild type, it did not do so in oxy2. Oxy2 is sensitive to copper chelation but resistant to high copper, suggesting that copper transport is decreased. The strain expresses large amounts of alternate oxidase in response to Cu-chelation, perhaps in response to defective, Cu-deprived cytochrome oxidase, and is resistant to the oxidant, plumbagin, under this condition, perhaps due to the high alternate oxidase. These phenotypes are similar to those of the mac1- mutant of Saccharomyces cerevisiae and the melanin-deficient grisea mutant of Podospora anserina, in which homologous transcriptional activators for the reductase and copper transporter genes are mutated. They constitute physiologic evidence that oxy2 is mutated in a homologous copper-related transcriptional activator of C. neoformans.
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PMID:Oxy2 as a transcriptional activator gene for copper uptake in Cryptococcus neoformans. 1547 57

Bacteria are exposed to reactive oxygen species from the environment and from those generated by aerobic metabolism. Catalases are heme proteins that detoxify H(2)O(2), and many bacteria contain more than one catalase enzyme. Also, the nonheme peroxidase alkyl hydroperoxide reductase (Ahp) is the major scavenger of endogenous H(2)O(2) in Escherichia coli. Here, we show that aerobically grown Bradyrhizobium japonicum cells express a single catalase activity. Four genes encoding putative catalases in the B. japonicum genome were identified, including a katG homolog encoding a catalase-peroxidase. Deletion of the katG gene resulted in loss of catalase activity in cell extracts and of exogenous H(2)O(2) consumption by whole cells. The katG strain had a severe aerobic growth phenotype but showed improved growth in the absence of O(2). By contrast, a B. japonicum ahpCD mutant grew well aerobically and consumed H(2)O(2) at wild-type rates. A heme-deficient hemA mutant expressed about one-third of the KatG activity as the wild type but grew well aerobically and scavenged low concentrations of exogenous H(2)O(2). However, cells of the hemA strain were deficient in consumption of high concentrations of H(2)O(2) and were very sensitive to killing by short exposure to H(2)O(2). In addition, KatG activity did not decrease as a result of mutation of the gene encoding the transcriptional activator OxyR. We conclude that aerobic metabolism produces toxic levels of H(2)O(2) in B. japonicum, which is detoxified primarily by KatG. Furthermore, the katG level sufficient for detoxification does not require OxyR.
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PMID:KatG is the primary detoxifier of hydrogen peroxide produced by aerobic metabolism in Bradyrhizobium japonicum. 1554 58

Nitric oxide reduction in Ralstonia eutropha H16 is catalysed by the quinol-dependent NO reductase NorB. norB and the adjacent norA form an operon that is controlled by the sigma(54)-dependent transcriptional activator NorR in response to NO. A NorR derivative containing MalE in place of the N-terminal domain binds to a 73 bp region upstream of norA that includes three copies of the putative upstream activator sequence GGT-(N(7))-ACC. Mutations altering individual bases of this sequence resulted in an 80-90% decrease in transcriptional activation by wild-type NorR. Similar motifs are present in several proteobacteria upstream of genes encoding proteins of NO metabolism. The N-terminal domain of NorR contains a GAF module and is hypothesized to interact with a signal molecule. A NorR derivative lacking this domain activates the norAB promoter constitutively. Amino acid exchanges within the GAF module identified a cysteine residue that is essential for promoter activation by NorR. Signal sensing by NorR is negatively modulated by the iron-containing protein NorA.
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PMID:Transcriptional regulation of nitric oxide reduction in Ralstonia eutropha H16. 1566 4


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