Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bacillus anthracis, a bioterrorism threat as well as an agricultural concern, has complex mechanisms for regulation of its major virulence factors. Genome searches identified the putative two-component system that we designated Bacillus anthracis respiratory response (Brr)A-BrrB. A brrA deletion strain was constructed, and real-time reverse transcriptase polymerase chain reaction and Western blot analysis were used to assess the effect of BrrA-BrrB on levels of virulence factors, the regulator atxA, and growth characteristics. When brrA was deleted, the genes for anthrax toxins (lethal factor, protective antigen, and edema factor) where expressed 4-6-log10-fold less than in the parent Sterne strain. The global regulator atxA was downregulated when compared to atxA in the Sterne strain. Thus, the BrrA-BrrB two-component system positively regulates B. anthracis toxin genes as well as the atxA regulator. Aerobic growth was not affected by the DeltabrrA mutation, but colonies showed differences in morphology, the mutant did not sporulate, and the strain lost the ability to synthesize cytochrome aa3. Gel-shift mobility assays demonstrated that BrrA bound to the promoters of genes for both protective antigen and cytochrome aa3, demonstrating that BrrA is a transcription factor. BrrA-BrrB has sequence similarity with the virulence regulator SrrA-SrrB in Staphylococcus aureus and the aerobic/anaerobic regulator, ResD-ResE, in B. subtilis, and appears to share regulatory mechanisms with ResD-ResE.
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PMID:The two-component system Bacillus respiratory response A and B (BrrA-BrrB) is a virulence factor regulator in Bacillus anthracis. 1753 38

Antiretroviral nucleoside reverse transcriptase inhibitors (NRTIs), given to human immunodeficiency virus-1-infected pregnant women to prevent vertical viral transmission, have caused mitochondrial dysfunction in some human infants. Here, we examined mitochondrial integrity in skeletal muscle from offspring of pregnant retroviral-free Erythrocebus patas dams administered human-equivalent NRTI doses for the last 10 weeks of gestation or for 10 weeks of gestation and 6 weeks after birth. Exposures included no drug, Zidovudine (AZT), Lamivudine (3TC), AZT/3TC, AZT/Didanosine (ddI), and Stavudine (d4T)/3TC. Offspring were examined at birth (n=3 per group) and 1 year (n=4 per group, not including 3TC alone). Circulating levels of creatine kinase were elevated at 1 year in the d4T/3TC-exposed group. Measurement of oxidative phosphorylation enzyme activities (complexes I, II, and IV) revealed minimal NRTI-induced changes at birth and at 1 year. Histochemistry for complex IV activity showed abnormal staining with activity depletion at birth and 1 year in groups exposed to AZT alone and to the 2-NRTI combinations. Electron microscopy of skeletal muscle at birth and 1 year of age showed mild to severe mitochondrial damage in all the NRTI-exposed groups, with 3TC inducing mild damage and the 2-NRTI combinations inducing extensive damage. At birth, mitochondrial DNA (mtDNA) was depleted by approximately 50% in groups exposed to AZT alone and the 2-NRTI combinations. At 1 year, the mtDNA levels had increased but remained significantly below normal. Therefore, skeletal muscle mitochondrial compromise occurs at birth and persists at 1 year of age (46 weeks after the last NRTI exposure) in perinatally exposed young monkeys, suggesting that similar events may occur in NRTI-exposed human infants.
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PMID:Erythrocebus patas monkey offspring exposed perinatally to NRTIs sustain skeletal muscle mitochondrial compromise at birth and at 1 year of age. 1754 13

Cyanobacterial Atx1 is a copper chaperone which interacts with two copper-transporting ATPases to assist copper supply to plastocyanin and cytochrome oxidase. ZiaA is a Zn(2+)-exporting ATPase and ziaA expression is regulated by ZiaR. Here we show that gene expression from the ziaA operator promoter, monitored using reverse transcriptase PCR and lacZ fusions, is elevated in Deltaatx1 mutants. Although Cu(+) tightly binds recombinant ZiaR in vitro, Cu(+) is less effective at dissociating ZiaR-DNA complexes than Zn(2+) and crucially ziaA expression responds to Zn(2+) but not copper in both wild-type and Deltaatx1 cells. Consistent with enhanced expression of ZiaA, Deltaatx1 cells have slightly elevated Zn(2+) resistance. Recombinant Zn(2+)-Atx1 is recovered from Zn(2+)-supplemented Escherichia coli and even after copper supplementation substantial amounts of Zn(2+)-Atx1 are isolated. Taken together, these data suggest that Zn(2+)-Atx1 can form in vivo.
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PMID:Interaction between cyanobacterial copper chaperone Atx1 and zinc homeostasis. 1954 24

Using differential display reverse transcriptase polymerase chain reaction, we detected 11 differentially expressed genes between top round and loin muscle in Korean cattle (Hanwoo). In the loin muscle, the lightness (L*) value (P<0.01) and marbling fat content (P<0.01), which are important factors in determining meat quality, were higher than in top round muscle. Three of the 11 genes were validated as significant genes between two types of muscle by real-time polymerase chain reaction (P<0.05). To determine whether the three genes were associated with meat quality traits, a regression analysis was preformed. The result demonstrated that two genes (NADH dehydrogenase 2 and cytochrome oxidase III), which are involved in oxidative phosphorylation in mitochondria, were significantly correlated with marbling fat content in the loin muscle (P<0.01), while two genes were not significant with marbling fat content in top round muscle. No significant effects for two genes on other meat quality traits such as meat color (redness and yellowness value), Warner-Bratzler shear force, and water-holding capacity were detected in this study.
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PMID:Gene expression profiling of metabolism-related genes between top round and loin muscle of Korean cattle (Hanwoo). 1987 21

HIV-1 reverse transcriptase (RT) is targeted by multiple drugs. RT mutations that confer resistance to nucleoside RT inhibitors (NRTIs) emerge during clinical use. Q151M and four associated mutations, A62V, V75I, F77L, and F116Y, were detected in patients failing therapies with dideoxynucleosides (didanosine [ddI], zalcitabine [ddC]) and/or zidovudine (AZT). The cluster of the five mutations is referred to as the Q151M complex (Q151Mc), and an RT or virus containing Q151Mc exhibits resistance to multiple NRTIs. To understand the structural basis for Q151M and Q151Mc resistance, we systematically determined the crystal structures of the wild-type RT/double-stranded DNA (dsDNA)/dATP (complex I), wild-type RT/dsDNA/ddATP (complex II), Q151M RT/dsDNA/dATP (complex III), Q151Mc RT/dsDNA/dATP (complex IV), and Q151Mc RT/dsDNA/ddATP (complex V) ternary complexes. The structures revealed that the deoxyribose rings of dATP and ddATP have 3'-endo and 3'-exo conformations, respectively. The single mutation Q151M introduces conformational perturbation at the deoxynucleoside triphosphate (dNTP)-binding pocket, and the mutated pocket may exist in multiple conformations. The compensatory set of mutations in Q151Mc, particularly F116Y, restricts the side chain flexibility of M151 and helps restore the DNA polymerization efficiency of the enzyme. The altered dNTP-binding pocket in Q151Mc RT has the Q151-R72 hydrogen bond removed and has a switched conformation for the key conserved residue R72 compared to that in wild-type RT. On the basis of a modeled structure of hepatitis B virus (HBV) polymerase, the residues R72, Y116, M151, and M184 in Q151Mc HIV-1 RT are conserved in wild-type HBV polymerase as residues R41, Y89, M171, and M204, respectively; functionally, both Q151Mc HIV-1 and wild-type HBV are resistant to dideoxynucleoside analogs.
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PMID:Structural Insights into HIV Reverse Transcriptase Mutations Q151M and Q151M Complex That Confer Multinucleoside Drug Resistance. 2839 46


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