Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The histone-like dimeric HU protein of Escherichia coli is encoded by two closely related genes, hupA and hupB. We show here that expression from the single hupA promoter and from the three hupB promoters varies during growth phase. The weak hupB-P4 promoter is active immediately after dilution. Transcription of the hupA gene is activated early in logarithmic phase. A little later, at mid to late exponential phase, RNA originating at the hupB-P2 promoter is detected. The hupB-P3 promoter is activated last when the cells enter stationary phase. Although the hup mRNAs are unstable, the HU protein is very stable so that the variations in the mRNAs synthesis are reflected in the level of the two HU subunits and in the composition of HU dimers. Cells growing exponentially contain a mixture of homodimeric alpha 2 and heterodimeric alpha beta but no beta 2 is detected. In stationary cells, the predominant form is the heterodimer alpha beta. The presence of the heterodimeric form is required for optimal survival of E. coli after prolonged starvation. The three forms of HU are not equivalent, since beta 2 is incapable of promoting formation of DNA supercoiling like alpha beta and alpha 2 do. The putative roles of each form of HU are discussed.
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PMID:Variation in HU composition during growth of Escherichia coli: the heterodimer is required for long term survival. 936 49

Glucocorticoids and their receptor (GR) play a key role in perinatal gene induction. In the liver, the GR is essential for the neonatal induction of a number of genes, including that coding for tyrosine aminotransferase (TAT). To assess the function of the GR in the perinatal period, we have compared the activity of two types of glucocorticoid responsive elements in transgenic mice; one is the Tat gene glucocorticoid-responsive unit (GRU), an assembly of numerous binding sites for transcription factors, including the GR; the other is a simple dimer of high-affinity GR binding sites (GREs). Both elements confer strong glucocorticoid response in the adult liver. However, only the Tat GRUs are able to promote neonatal induction; the GRE dimer is unresponsive. Because this dimer is responsive to glucocorticoid administration in the neonate, the absence of neonatal induction is not due to the inactivity of the GR at this stage. At birth, the neonate has to withstand a brief period of starvation and hypoglycemia, a nutritional and hormonal situation that resembles fasting in the adult. In transgenic mice, the responses at birth and after fasting in the adult are similar: the Tat GRUs but not the dimeric GREs are activated. Our results show that, in rodents, glucocorticoids are not sufficient for neonatal gene induction in the liver and support the conclusion that the hypoglycemia at birth is the main trigger for expression.
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PMID:Glucocorticoids are insufficient for neonatal gene induction in the liver. 957 33

Herein we report on the kinetic and protein expression of glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase, and malic enzyme (ME) in the liver of the trout (Oncorhynchus mykiss) during a long-term starvation-refeeding cycle. Starvation significantly depressed the activity of these enzymes by almost 60%, without changing the Michaelis constant. The time response to this nutritional stimulus increased with fish weight. The sharp decline in G6PDH and ME activities was due to a specific protein-repression phenomenon, as demonstrated by molecular and immunohistochemical analyses. Also, the dimeric banding pattern of liver G6PDH shifted from the fully reduced and partially oxidized forms, predominant in control, to a fully oxidized form, more sensitive to proteolytic inactivation. Refeeding caused opposite effects in both protein concentration and enzyme activities of about twice the control values in the first stages, later reaching the normal enzyme activity levels. Additionally, the partially oxidized form of G6PDH increased. The kinetics of these enzymes were examined in relation to the various metabolic roles of NADPH. These results clearly indicate that trout liver undergoes protein repression-induction processes under these two contrasting nutritional conditions.
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PMID:Impact of starvation-refeeding on kinetics and protein expression of trout liver NADPH-production systems. 960 11

The cDNA and the chromosomal locus of the aroC gene of Aspergillus nidulans were cloned and is the first representative of a filamentous fungal gene encoding chorismate mutase (EC 5.4.99.5), the enzyme at the first branch point of aromatic amino acid biosynthesis. The aroC gene complements the Saccharomyces cerevisiae aro7Delta as well as the A. nidulans aroC mutation. The gene consists of three exons interrupted by two short intron sequences. The expressed mRNA is 0.96 kilobases in length and aroC expression is not regulated on the transcriptional level under amino acid starvation conditions. aroC encodes a monofunctional polypeptide of 268 amino acids. Purification of this 30-kDa enzyme allowed determination of its kinetic parameters (k(cat) = 82 s(-1), n(H) = 1. 56, [S](0.5) = 2.3 mM), varying pH dependence of catalytic activity in different regulatory states, and an acidic pI value of 4.7. Tryptophan acts as heterotropic activator and tyrosine as negative acting, heterotropic feedback-inhibitor with a K(i) of 2.8 microM. Immunological data, homology modeling, as well as electron microscopy studies, indicate that this chorismate mutase has a dimeric structure like the S. cerevisiae enzyme. Site-directed mutagenesis of a crucial residue in loop220s (Asp(233)) revealed differences concerning the intramolecular signal transduction for allosteric regulation of enzymatic activity.
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PMID:The aroC gene of Aspergillus nidulans codes for a monofunctional, allosterically regulated chorismate mutase. 1042 95

A group of Cu,Zn-superoxide dismutases from pathogenic bacteria is characterized by histidine-rich N-terminal extensions that are in a highly exposed and mobile conformation. This feature allows these proteins to be readily purified in a single step by immobilized metal affinity chromatography. The Cu,Zn-superoxide dismutases from both Haemophilus ducreyi and Haemophilus parainfluenzae display anomalous absorption spectra in the visible region due to copper binding at the N-terminal region. Reconstitution experiments of copper-free enzymes demonstrate that, under conditions of limited copper availability, this metal ion is initially bound at the N-terminal region and subsequently transferred to an active site. Evidence is provided for intermolecular pathways of copper transfer from the N-terminal domain of an enzyme subunit to an active site located on a distinct dimeric molecule. Incubation with EDTA rapidly removes copper bound at the N terminus but is much less effective on the copper ion bound at the active site. This indicates that metal binding by the N-terminal histidines is kinetically favored, but the catalytic site binds copper with higher affinity. We suggest that the histidine-rich N-terminal region constitutes a metal binding domain involved in metal uptake under conditions of metal starvation in vivo. Particular biological importance for this domain is inferred by the observation that its presence enhances the protection offered by periplasmic Cu,Zn-superoxide dismutase toward phagocytic killing.
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PMID:A histidine-rich metal binding domain at the N terminus of Cu,Zn-superoxide dismutases from pathogenic bacteria: a novel strategy for metal chaperoning. 1136 56

In prokaryotes, incomplete or misfolded polypeptides emanating from a stalled ribosome are marked for degradation by the addition of an 11 residue peptide (AANDENYALAA) to their C terminus. Substrates containing this conserved degradation signal, the SsrA tag, are targeted to specific proteases including ClpXP and ClpAP. SspB was originally characterized as a stringent starvation protein and has been found to bind specifically to SsrA-tagged proteins and to enhance recognition of these proteins by the ClpXP degradation machine. Here, we report the crystal structures of SspB alone and in complex with an SsrA peptide. Unexpectedly, SspB exhibits a fold found in Sm-family RNA binding proteins. The dimeric SspB structures explain the key determinants for recognition of the SsrA tag and define a hydrophobic channel that may bind unfolded substrates.
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PMID:Structural basis of degradation signal recognition by SspB, a specificity-enhancing factor for the ClpXP proteolytic machine. 1288 94

Bacterial iron storage proteins such as ferritin serve as intracellular iron reserves. Members of the DNA protection during starvation (Dps) family of proteins are structurally related to ferritins, and their function is to protect the genome from iron-induced free radical damage. Some members of the Dps family bind DNA and are thought to do so only as fully assembled dodecamers. We present the cloning and characterization of a Dps homolog encoded by the radiation-resistant eubacterium Deinococcus radiodurans and show that DNA binding does not require its assembly into a dodecamer. D.radiodurans Dps-1, the product of gene DR2263, adopts a stably folded conformation, as demonstrated by circular dichroism spectroscopy, and undergoes a transition to a disordered state with a melting temperature of 69.2(+/-0.1) degrees C. While a dimeric form of Dps-1 is observed under low-salt conditions, a dodecameric assembly is highly favored at higher concentrations of salt. Both oligomeric forms of Dps-1 exhibit ferroxidase activity, and Fe(II) oxidation/mineralization is seen for dodecameric Dps-1. Notably, addition of Ca(2+) (to millimolar concentrations) to dodecameric Dps-1 can result in the reduction of bound Fe(III). Dimeric Dps-1 protects DNA from both hydroxyl radical cleavage and from DNase I-mediated cleavage; however, dodecameric Dps-1 is unable to provide efficient protection against hydroxyl radical-mediated DNA cleavage. While dodecameric Dps-1 does bind DNA, resulting in formation of large aggregates, cooperative DNA binding by dimeric Dps-1 leads to formation of protein-DNA complexes of finite stoichiometry.
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PMID:Differential DNA binding and protection by dimeric and dodecameric forms of the ferritin homolog Dps from Deinococcus radiodurans. 1575 46

Upon iron limitation, Bacillus subtilis secretes the catecholic trilactone (2,3-dihydroxybenzoate-glycine-threonine)3 siderophore bacillibactin (BB) for ferric iron scavenging. Here, we show that ferri-BB uptake is mediated by the FeuABC transporter and that YuiI, a novel trilactone hydrolase, catalyses ferri-BB hydrolysis leading to cytosolic iron release. Among several Fur-regulated ABC transport mutants, only DeltafeuABC exhibited impaired growth during iron starvation. Quantification of intra- and extracellular (ferri)-BB in iron-depleted DeltafeuABC cultures revealed a fourfold increase of the extracellular siderophore concentration, confirming a blocked ferri-BB uptake in the absence of FeuABC. Ferri-BB was found to bind selectively to the periplasmic binding protein FeuA (Kd = 57 +/- 1 nM), proving high-affinity transport of the iron-charged siderophore. During iron starvation, a DeltayuiI mutant displayed impaired growth and strong intracellular (30-fold) and extracellular (6.5-fold) (ferri)-BB accumulation. Kinetic studies in vitro revealed that YuiI hydrolyses both BB and ferri-BB. While BB hydrolysis led to strong accumulation of the tri- and dimeric reaction intermediates, ferri-BB hydrolysis yielded exclusively the monomeric reaction product and occurred with a 25-fold higher catalytic efficiency than BB single hydrolysis. Thus, ferri-BB was the preferred substrate of the YuiI esterase whose gene locus was designated besA.
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PMID:Ferri-bacillibactin uptake and hydrolysis in Bacillus subtilis. 1688 43

Lipocalins, a widespread multifunctional family of small proteins (15-25kDa) have been first described in eukaryotes and more recently in Gram-negative bacteria. Bacterial lipocalins belonging to class I are outer membrane lipoproteins, among which Blc from E. coli is the better studied. Blc is expressed under conditions of starvation and high osmolarity, conditions known to exert stress on the cell envelope. The structure of Blc that we have previously solved (V. Campanacci, D. Nurizzo, S. Spinelli, C. Valencia, M. Tegoni, C. Cambillau, FEBS Lett. 562 (2004) 183-188.) suggested its possible role in binding fatty acids or phospholipids. Both physiological and structural data on Blc, therefore, point to a role in storage or transport of lipids necessary for membrane maintenance. In order to further document this hypothesis for Blc function, we have performed binding studies using fluorescence quenching experiments. Our results indicate that dimeric Blc binds fatty acids and phospholipids in a micromolar K(d) range. The crystal structure of Blc with vaccenic acid, an unsaturated C18 fatty acid, reveals that the binding site spans across the Blc dimer, opposite to its membrane anchored face. An exposed unfilled pocket seemingly suited to bind a polar group attached to the fatty acid prompted us to investigate lyso-phospholipids, which were found to bind in a nanomolar K(d) range. We discuss these findings in terms of a potential role for Blc in the metabolism of lysophospholipids generated in the bacterial outer membrane.
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PMID:The membrane bound bacterial lipocalin Blc is a functional dimer with binding preference for lysophospholipids. 1692 Jan 9

Several Bacillus strains secrete phytase, an enzyme catalyzing dephosphorylation of myo-inositol hexakisphosphate (phytate). We identified the phyC (phytase) gene from environmental Bacillus amyloliquefaciens FZB45 as a member of the phosphate starvation-inducible PhoPR regulon. In vivo and in vitro assays revealed that PhoP approximately P is essential for phyC transcription. The transcriptional start site was identified downstream of a sigmaA-like promoter region located 27 bp upstream of the probable translation ATG start codon. Inspection of the phyC promoter sequence revealed an unusual structure. The -35 and -10 regions are separated by a window of 21 bp. A pair of tandemly repeated PhoP TT(T/A/C)ACA binding boxes was located within and upstream of the -35 consensus promoter region. A single PhoP box was found within the -10 consensus promoter region. DNase I footprinting experiments performed with isolated PhoP confirmed that PhoP approximately P binds at two sites overlapping with the phyC -35 and -10 consensus promoter region. While binding of dimeric PhoP approximately P at -35 is essential for activation of the phyC promoter, binding of PhoP approximately P at -10 suppresses promoter activity. A sixfold enhancement of phyC gene expression was registered after T:G substitution of nucleotide -13 (mutant MUT13), which eliminates PhoP binding at the single PhoP box without impairing the -10 consensus sequence. Moreover, MUT13 also expressed phyC during phosphate-replete growth, suggesting that the repressing effect due to binding of PhoP approximately P at -10 was abolished. A model is presented in which transcription initiation of phyC is positively and negatively affected by the actual concentration of the PhoP approximately P response regulator.
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PMID:Dual role of the PhoP approximately P response regulator: Bacillus amyloliquefaciens FZB45 phytase gene transcription is directed by positive and negative interactions with the phyC promoter. 1698 Apr 98


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