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)

The ability of a pathogen to cause infection depends on successful colonization of the host, which, in turn, requires adaptation to various challenges presented by that host. For example, host immune cells use a variety of mechanisms to control infection by bacterial pathogens, including the production of bactericidal reactive oxygen species. Prokaryotic and eukaryotic cells have developed ways of protecting themselves against this oxidative damage; for instance, Borrelia burgdorferi alters the expression of oxidative-stress-related proteins, such as a Dps/Dpr homolog NapA (BB0690), in response to increasing levels of oxygen and reactive oxygen species. These stress-related genes appear to be regulated by a putative metal-dependent DNA-binding protein (BB0647) that has 50.7% similarity to the peroxide-specific stress response repressor of Bacillus subtilis, PerR. We overexpressed and purified this protein from Escherichia coli and designated it Borrelia oxidative stress regulator, BosR. BosR bound to a 50-nt region 180 bp upstream of the napA transcriptional start site and required DTT and Zn2+ for optimal binding. Unlike the Bacillus subtilis PerR repressor, BosR did not require Fe2+ and Mn2+ for binding, and oxidizing agents, such as t-butyl peroxide, enhanced, not eliminated, BosR binding to the napA promoter region. Surprisingly, transcriptional fusion analysis indicated that BosR exerted a positive regulatory effect on napA that is inducible with t-butyl peroxide. On the basis of these data, we propose that, despite the similarity to PerR, BosR functions primarily as a transcriptional activator, not a repressor of oxidative stress response, in B. burgdorferi.
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PMID:Borrelia oxidative stress response regulator, BosR: a distinctive Zn-dependent transcriptional activator. 1297 27

Avicins are a recently discovered family of plant-derived terpenoid molecules that possess proapoptotic, antiinflammatory, and cytoprotective properties in mammalian cells. Previous work demonstrating that avicins can exert their effects by suppressing or activating the redox-sensitive transcription factors NF-kappaB and nuclear factor-erythroid 2 p45-related factor (Nrf2), respectively, has raised the idea that they may react with critical cysteine residues. To understand the molecular mechanism through which avicins regulate protein function, we examined their effects on the paradigmatic redox-responsive transcriptional activator, OxyR of Escherichia coli, which protects bacterial cells against oxidative and nitrosative stresses. In vitro transcription assays demonstrated that avicins activate OxyR and its target genes katG and oxyS in a DTT-reversible manner. In addition, katG-dependent hydroperoxidase I activity was enhanced in avicin-treated bacteria. Mass spectrometric analysis of activated OxyR revealed thioesterification of the critical regulatory cysteine, Cys-199, to an avicin fragment comprising the outer monoterpene side chain. Our results indicate that avicinylation can induce adaptive responses that protect cells against oxidative or nitrosative stress. More generally, transesterification may represent a previously undescribed thiol-directed posttranslational modification, which extends the code for redox regulation of protein function.
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PMID:Avicinylation (thioesterification): a protein modification that can regulate the response to oxidative and nitrosative stress. 1603 Jan 51