Abstract：
:Ethionamide is an antituberculous drug for the treatment of multidrug-resistant Mycobacterium tuberculosis. This antibiotic requires activation by the monooxygenase EthA to exert its activity. Production of EthA is controlled by the transcriptional repressor EthR, a member of the TetR family. The sensitivity of M. tuberculosis to ethionamide can be artificially enhanced using synthetic ligands of EthR that allosterically inactivate its DNA-binding activity. Comparison of several structures of EthR co-crystallized with various ligands suggested that the structural reorganization of EthR resulting in its inactivation is controlled by a limited portion of the ligand-binding-pocket. In silico simulation predicted that mutation G106W may mimic ligands. X-ray crystallography of variant G106W indeed revealed a protein structurally similar to ligand-bound EthR. Surface plasmon resonance experiments established that this variant is unable to bind DNA, while thermal shift studies demonstrated that mutation G106W stabilizes EthR as strongly as ligands. Proton NMR of the methyl regions showed a lesser contribution of exchange broadening upon ligand binding, and the same quenched dynamics was observed in apo-variant G106W. Altogether, we here show that the area surrounding Gly106 constitutes the molecular switch involved in the conformational reorganization of EthR. These results also shed light on the mechanistic of ligand-induced allosterism controlling the DNA binding properties of TetR family repressors.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Carette X,Blondiaux N,Willery E,Hoos S,Lecat-Guillet N,Lens Z,Wohlkönig A,Wintjens R,Soror SH,Frénois F,Dirié B,Villeret V,England P,Lippens G,Deprez B,Locht C,Willand N,Baulard ARdoi
10.1093/nar/gkr1113subject
Has Abstractpub_date
2012-04-01 00:00:00pages
3018-30issue
7eissn
0305-1048issn
1362-4962pii
gkr1113journal_volume
40pub_type
杂志文章abstract：:We have examined the formation of alternate strand triple-helices at the target sequence A11(TC)6.(GA)6T11 using the oligonucleotides T11(AG)6 and T11(TG)6, by DNase I footprinting. These third strands were designed so as to form parallel T.AT triplets together with antiparallel G.GC and A.AT or T.AT triplets. We find...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/22.19.3977
更新日期：1994-09-25 00:00:00
abstract：:In highly oncogenic adenovirus (Ad) 12-transformed cells, major histocompatibility complex (MHC) class I gene expression is down-regulated by the products of the viral E1A oncogene at the level of initiation of transcription. However, class I gene expression is unaltered or elevated in non-oncogenic Ad2- or Ad5-transf...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/22.22.4779
更新日期：1994-11-11 00:00:00
abstract：:Cellular RNA labeling strategies based on bioorthogonal chemical reactions are much less developed in comparison to glycan, protein and DNA due to its inherent instability and lack of effective methods to introduce bioorthogonal reactive functionalities (e.g. azide) into RNA. Here we report the development of a simple...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkv903
更新日期：2016-01-29 00:00:00
abstract：:We have modeled local DNA sequence parameters to search for DNA architectural motifs involved in transcription regulation and promotion within the Xenopus laevis ribosomal gene promoter and the intergenic spacer (IGS) sequences. The IGS was found to be shaped into distinct topological domains. First, intrinsic bends s...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/28.18.3433
更新日期：2000-09-15 00:00:00
abstract：:A simple and effective modified ethanol precipitation-based protocol is described for the preparation of DNA from ancient human bones. This method is fast and requires neither hazardous chemicals nor special devices. After the powdering and incubating of the bone samples Dextran Blue was added as a carrier for removin...
journal_title：Nucleic acids research
pub_type： 历史文章,杂志文章
doi：10.1093/nar/28.12.e67
更新日期：2000-06-15 00:00:00
abstract：:Proper cytokine gene expression is essential in development, homeostasis and immune responses. Studies on the transcriptional control of cytokine genes have mostly focused on highly researched transcription factors (TFs) and cytokines, resulting in an incomplete portrait of cytokine gene regulation. Here, we used enha...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkaa1055
更新日期：2020-12-02 00:00:00
abstract：:RNA editing of miRNAs, especially in the seed region, adds another layer to miRNA mediated gene regulation which can modify its targets, altering cellular signaling involved in important processes such as differentiation. In this study, we have explored the role of miRNA editing in CD4(+) T cell differentiation. CD4(+...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkv752
更新日期：2015-09-18 00:00:00
abstract：:In Euplotes crassus millions of telomeres are synthesized during the sexual phase of the life cycle. Since these newly synthesized telomeres are longer than normal macronuclear telomeres, they must be trimmed to the mature size. We have examined the timing and mechanism of this trimming step. We have shown that a sudd...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/21.23.5366
更新日期：1993-11-25 00:00:00
abstract：:Uracil-Specific Exision Reagent (USER) fusion is a recently developed technique that allows for assembly of multiple DNA fragments in a few simple steps. However, designing primers for USER fusion is both tedious and time consuming. Here, we present the Primer Help for USER (PHUSER) software, a novel tool for designin...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkr394
更新日期：2011-07-01 00:00:00
abstract：:Cyclic AMP response element binding protein (CREB) activates transcription of cAMP response element (CRE)-containing promoters following an elevation of intracellular cAMP. Here we show that CREB and the highly related protein ATF-1 are also potent transcription inhibitors. Strikingly, CREB inhibits transcription of m...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/21.12.2907
更新日期：1993-06-25 00:00:00
abstract：:Human transcription factor IIIC contains a 55 kDa polypeptide which specifically interacts with the Adenovirus 2 VAI gene promoter and which mimics most of the DNA binding properties of the entire factor. The specificity and affinity of this protein:DNA interaction was demonstrated by: (i) Separation of purified fract...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/18.16.4743
更新日期：1990-08-25 00:00:00
abstract：:RNA polymerase III recognizes and pauses at its terminator, an oligo(dT) tract in non-template DNA, terminates 3' oligo(rU) synthesis within this sequence, and releases the RNA. The pol III subunit Rpc11p (C11) mediates RNA 3'-5' cleavage in the catalytic center of pol III during pausing. The amino and carboxyl region...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkr182
更新日期：2011-08-01 00:00:00
abstract：:With the development of High-Throughput Sequencing (HTS) thousands of human genomes have now been sequenced. Whenever different studies analyze the same genome they usually agree on the amount of single-nucleotide polymorphisms, but differ dramatically on the number of insertion and deletion variants (indels). Further...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkv677
更新日期：2015-09-03 00:00:00
abstract：:In Saccharomyces cerevisiae the majority of the genes for 5S rRNA lie within a 9kb rDNA sequence that is present as 100-200 tandemly-repeated copies on Chromosome XII. Following our observations that about 10% of yeast 5S rRNA exists as minor variant sequences, we screened a collection of yeast DNA fragments cloned in...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/12.10.4083
更新日期：1984-05-25 00:00:00
abstract：:Period2 (Per2) is an essential component of the mammalian clock mechanism and robust circadian expression of Per2 is essential for the maintenance of circadian rhythms. Although recent studies have shown that the circadian E2 enhancer (a non-canonical E-box) accounts for most of the circadian transcriptional drive of ...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkl868
更新日期：2007-01-01 00:00:00
abstract：:The Mouse Genome Database (MGD) (http://www.informatics.jax.org) one component of a community database resource for the laboratory mouse, a key model organism for interpreting the human genome and for understanding human biology. MGD strives to provide an extensively integrated information resource with experimental d...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkg047
更新日期：2003-01-01 00:00:00
abstract：:The RNA 3D Structure-to-Multiple Sequence Alignment Server (R3D-2-MSA) is a new web service that seamlessly links RNA three-dimensional (3D) structures to high-quality RNA multiple sequence alignments (MSAs) from diverse biological sources. In this first release, R3D-2-MSA provides manual and programmatic access to cu...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkv543
更新日期：2015-07-01 00:00:00
abstract：:The ability to store and interconnect all available information on proteins is crucial to modern biological research. Accordingly, the Universal Protein Resource (UniProt) plays an increasingly important role by providing a stable, comprehensive, freely accessible central resource on protein sequences and functional a...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkl929
更新日期：2007-01-01 00:00:00
abstract：:We have isolated a human cDNA (kup), encoding a new protein with two distantly spaced zinc fingers of the C2H2 type. This gene is highly conserved in mammals and is expressed mainly in hematopoietic cells and testis. Its expression was not higher in the various transformed cells tested than in the normal corresponding...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/19.7.1431
更新日期：1991-04-11 00:00:00
abstract：:GC content bias describes the dependence between fragment count (read coverage) and GC content found in Illumina sequencing data. This bias can dominate the signal of interest for analyses that focus on measuring fragment abundance within a genome, such as copy number estimation (DNA-seq). The bias is not consistent b...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gks001
更新日期：2012-05-01 00:00:00
abstract：:A small library of 49 peptide-oligonucleotide conjugates were synthesized to explore the influence of various peptide side chains on the hybridization properties of the DNA. An invariant 8mer oligonucleotide was coupled to a peptide portion that contained a five residue variable region composed of the cationic amino a...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/26.13.3136
更新日期：1998-07-01 00:00:00
abstract：:Genome-wide expression profiling is a powerful tool for implicating novel gene ensembles in cellular mechanisms of health and disease. The most popular platform for genome-wide expression profiling is the Affymetrix GeneChip. However, its selection of probes relied on earlier genome and transcriptome annotation which ...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gni179
更新日期：2005-11-10 00:00:00
abstract：:The initiation region of the MS2 replicase cistron can be isolated as a fragment 59 bases in length protected from RNAase by the binding of the coat protein which serves as a translational repressor. This fragment MS2 R(-53 leads to 6) starts 53 bases before the initiation codon and retains full activity in binding ri...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/6.5.1761
更新日期：1979-01-01 00:00:00
abstract：:Multicellular organismal development is controlled by a complex network of transcription factors, promoters and enhancers. Although reliable computational and experimental methods exist for enhancer detection, prediction of their target genes remains a major challenge. On the basis of available literature and ChIP-seq...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkq1081
更新日期：2011-04-01 00:00:00
abstract：:E. coli can be transformed to extremely high efficiencies by subjecting a mixture of cells and DNA to brief but intense electrical fields of exponential decay waveform (electroporation). We have obtained 10(9) to 10(10) transformants/micrograms with strains LE392 and DH5 alpha, and plasmids pUC18 and pBR329. The proce...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/16.13.6127
更新日期：1988-07-11 00:00:00
abstract：:A simple, reproducible affinity chromatography method has been adapted for separation of high molecular weight supercoiled circular molecules from mammalian cells. Electron microscopic analysis of EB viral DNA obtained by this method, from the non-producer Burkitt's lymphoma line Raji, revealed monomer-sized viral mol...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/15.24.10345
更新日期：1987-12-23 00:00:00
abstract：:Homeodomains appear to be one of the most frequently employed DNA-binding domains in a superfamily of transacting factors. It is likely that during evolution several sub-types of homeodomain have evolved from a common ancestral domain, resulting in distinct but closely related DNA-binding preferences. Here we describe...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/22.7.1202
更新日期：1994-04-11 00:00:00
abstract：:The transcriptional promoter of satellite 2 from the eastern newt, Notophthalmus viridescens, was analyzed by assaying the activity of deleted or mutated satellite 2 clones in Xenopus laevis oocytes. Two elements in the promoter were found to be important for transcription. These elements have sequences that are simil...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/22.22.4697
更新日期：1994-11-11 00:00:00
abstract：:The mode of action of regulated promoters is largely determined by kinetic parameters which govern the interaction between promoters and proteins involved in induction and repression of transcription. To gain insight into the interplay between positively and negatively acting transcriptional regulators, in this case A...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/29.18.3873
更新日期：2001-09-15 00:00:00
abstract：:When B cells differentiate into plasma cells, there is a large increase in the cellular content of mRNA coding for immunoglobulin. This increase cannot be fully accounted for by the increase in rate of transcription of the genes. We have investigated the possibility that the half-life of mu heavy chain mRNA increases ...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/17.24.10439
更新日期：1989-12-25 00:00:00
