pH-Dependent DNA Distortion and Repression of Gene Expression by Pectobacterium atrosepticum PecS.

Abstract:

:Transcriptional activity is exquisitely sensitive to changes in promoter DNA topology. Transcription factors may therefore control gene activity by modulating the relative positioning of -10 and -35 promoter elements. The plant pathogen Pectobacterium atrosepticum, which causes soft rot in potatoes, must alter gene expression patterns to ensure growth in planta. In the related soft-rot enterobacterium Dickeya dadantii, PecS functions as a master regulator of virulence gene expression. Here, we report that P. atrosepticum PecS controls gene activity by altering promoter DNA topology in response to pH. While PecS binds the pecS promoter with high affinity regardless of pH, it induces significant DNA distortion only at neutral pH, the pH at which the pecS promoter is repressed in vivo. At pH ∼8, DNA distortions are attenuated, and PecS no longer represses the pecS promoter. A specific histidine (H142) located in a crevice between the dimerization- and DNA-binding regions is required for pH-dependent changes in DNA distortion and repression of gene activity, and mutation of this histidine renders the mutant protein incapable of repressing the pecS promoter. We propose that protonated PecS induces a DNA conformation at neutral pH in which -10 and -35 promoter elements are suboptimally positioned for RNA polymerase binding; on deprotonation of PecS, binding is no longer associated with significant changes in DNA conformation, allowing gene expression. We suggest that this mode of gene regulation leads to differential expression of the PecS regulon in response to alkalinization of the plant apoplast.

journal_name

ACS Chem Biol

journal_title

ACS chemical biology

authors

Deochand DK,Meariman JK,Grove A

doi

10.1021/acschembio.6b00168

subject

Has Abstract

pub_date

2016-07-15 00:00:00

pages

2049-56

issue

7

eissn

1554-8929

issn

1554-8937

journal_volume

11

pub_type

杂志文章
  • A small-molecule probe of the histone methyltransferase G9a induces cellular senescence in pancreatic adenocarcinoma.

    abstract::Post-translational modifications of histones alter chromatin structure and play key roles in gene expression and specification of cell states. Small molecules that target chromatin-modifying enzymes selectively are useful as probes and have promise as therapeutics, although very few are currently available. G9a (also ...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/cb300139y

    authors: Yuan Y,Wang Q,Paulk J,Kubicek S,Kemp MM,Adams DJ,Shamji AF,Wagner BK,Schreiber SL

    更新日期:2012-07-20 00:00:00

  • Biochemical and biophysical analysis of a chiral PqsD inhibitor revealing tight-binding behavior and enantiomers with contrary thermodynamic signatures.

    abstract::Antivirulence strategies addressing bacterial pathogenicity without exhibiting growth inhibition effects represent a novel approach to overcome today's crisis in antibiotic development. In recent studies, we examined various inhibitors of PqsD, an enzyme involved in formation of Pseudomonas aeruginosa cell-to-cell sig...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/cb400530d

    authors: Storz MP,Brengel C,Weidel E,Hoffmann M,Hollemeyer K,Steinbach A,Müller R,Empting M,Hartmann RW

    更新日期:2013-12-20 00:00:00

  • Douglas Weibel: using microfluidics for microbiology.

    abstract::The ubiquity of microorganisms is unparalleled in any other known organism. These creatures surround our outsides and colonize our insides, a fact that has been known for centuries. However, despite their prevalence and long study, many of their characteristics still remain largely unexplained, including how proteins ...

    journal_title:ACS chemical biology

    pub_type: 传,历史文章,杂志文章

    doi:10.1021/cb100179t

    authors: Brownlee C

    更新日期:2010-07-16 00:00:00

  • Histo-Blood Group Antigen Presentation Is Critical for Binding of Norovirus VLP to Glycosphingolipids in Model Membranes.

    abstract::Virus entry depends on biomolecular recognition at the surface of cell membranes. In the case of glycolipid receptors, these events are expected to be influenced by how the glycan epitope close to the membrane is presented to the virus. This presentation of membrane-associated glycans is more restricted than that of g...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/acschembio.7b00152

    authors: Nasir W,Frank M,Kunze A,Bally M,Parra F,Nyholm PG,Höök F,Larson G

    更新日期:2017-05-19 00:00:00

  • Construction of a rhythm transfer system that mimics the cellular clock.

    abstract::Creation of an artificial oscillating gene expression system is one of the most challenging issues in synthetic biology. Here, we constructed a simple system to manipulate gene expression patterns to be circadian, reflecting the intrinsic cellular clock, by fusing a core clock protein, BMAL1 or CLOCK, with a zinc fing...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/cb300432s

    authors: Imanishi M,Yamamoto K,Yamada H,Hirose Y,Okamura H,Futaki S

    更新日期:2012-11-16 00:00:00

  • Defined substrates for human embryonic stem cell growth identified from surface arrays.

    abstract::Methods for the rapid identification of defined cell growth conditions are lacking. This deficiency is a major barrier to the investigation and application of human embryonic stem (ES) cells. To address this problem, we developed a method for generating arrays of self-assembled monolayers (SAMs) in which each element ...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/cb700032u

    authors: Derda R,Li L,Orner BP,Lewis RL,Thomson JA,Kiessling LL

    更新日期:2007-05-22 00:00:00

  • Identification and Characterization of Dual Inhibitors of the USP25/28 Deubiquitinating Enzyme Subfamily.

    abstract::The ubiquitin proteasome system is widely postulated to be a new and important field of drug discovery for the future, with the ubiquitin specific proteases (USPs) representing one of the more attractive target classes within the area. Many USPs have been linked to critical axes for therapeutic intervention, and the f...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/acschembio.7b00334

    authors: Wrigley JD,Gavory G,Simpson I,Preston M,Plant H,Bradley J,Goeppert AU,Rozycka E,Davies G,Walsh J,Valentine A,McClelland K,Odrzywol KE,Renshaw J,Boros J,Tart J,Leach L,Nowak T,Ward RA,Harrison T,Andrews DM

    更新日期:2017-12-15 00:00:00

  • Errors in translation cause selective neurodegeneration.

    abstract::The 3D structure of a protein is determined by the unique sequence of amino acid residues comprising the polypeptide chain. Sequence changes can cause protein misfolding, a potentially toxic phenomenon implicated in various neurodegenerative disorders. In a recent paper, translational misincorporation is proposed to b...

    journal_title:ACS chemical biology

    pub_type: 杂志文章,评审

    doi:10.1021/cb6004068

    authors: Rochet JC

    更新日期:2006-10-24 00:00:00

  • Stabilizing the pro-apoptotic BimBH3 helix (BimSAHB) does not necessarily enhance affinity or biological activity.

    abstract::An attractive approach for developing therapeutic peptides is to enhance binding to their targets by stabilizing their α-helical conformation, for example, stabilized BimBH3 peptides (BimSAHB) designed to induce apoptosis. Unexpectedly, we found that such modified peptides have reduced affinity for their targets, the ...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/cb3005403

    authors: Okamoto T,Zobel K,Fedorova A,Quan C,Yang H,Fairbrother WJ,Huang DC,Smith BJ,Deshayes K,Czabotar PE

    更新日期:2013-02-15 00:00:00

  • Stable RAGE-heparan sulfate complexes are essential for signal transduction.

    abstract::RAGE (Receptor for Advanced Glycation End-Products) has emerged as a major receptor that mediates vascular inflammation. Signaling through RAGE by damage-associated molecular pattern molecules often leads to uncontrolled inflammation that exacerbates the impact of the underlying disease. Oligomerization of RAGE is bel...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/cb4001553

    authors: Xu D,Young JH,Krahn JM,Song D,Corbett KD,Chazin WJ,Pedersen LC,Esko JD

    更新日期:2013-07-19 00:00:00

  • High Throughput Screen Identifies Small Molecule Effectors That Modulate Thin Filament Activation in Cardiac Muscle.

    abstract::Current therapeutic interventions for both heart disease and heart failure are largely insufficient and associated with undesired side effects. Biomedical research has emphasized the role of sarcomeric protein function for the normal performance and energy efficiency of the heart, suggesting that directly targeting th...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/acschembio.0c00908

    authors: Parijat P,Kondacs L,Alexandrovich A,Gautel M,Cobb AJA,Kampourakis T

    更新日期:2021-01-15 00:00:00

  • Structure-Based Mutagenesis of Phycobiliprotein smURFP for Optoacoustic Imaging.

    abstract::Photo- or optoacoustics (OA) imaging is increasingly being used as a non-invasive imaging method that can simultaneously reveal structure and function in deep tissue. However, the most frequent transgenic OA labels are current fluorescent proteins that are not optimized for OA imaging. Thus, they lack OA signal streng...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/acschembio.9b00299

    authors: Fuenzalida Werner JP,Mishra K,Huang Y,Vetschera P,Glasl S,Chmyrov A,Richter K,Ntziachristos V,Stiel AC

    更新日期:2019-09-20 00:00:00

  • Site-Specific Radiofluorination of Biomolecules with 8-[(18)F]-Fluorooctanoic Acid Catalyzed by Lipoic Acid Ligase.

    abstract::New methodologies for site-specifically radiolabeling proteins with (18)F are required to generate high quality radiotracers for preclinical and clinical applications with positron emission tomography. Herein, we report an approach by which we use lipoic acid ligase (LplA) to conjugate [(18)F]-fluorooctanoic acid to a...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/acschembio.6b00172

    authors: Drake CR,Sevillano N,Truillet C,Craik CS,VanBrocklin HF,Evans MJ

    更新日期:2016-06-17 00:00:00

  • Exploiting structural analysis, in silico screening, and serendipity to identify novel inhibitors of drug-resistant falciparum malaria.

    abstract::Plasmodium falciparum thymidylate synthase-dihydrofolate reductase (TS-DHFR) is an essential enzyme in folate biosynthesis and a major malarial drug target. This bifunctional enzyme thus presents different design approaches for developing novel inhibitors against drug-resistant mutants. We performed a high-throughput ...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/cb8002804

    authors: Dasgupta T,Chitnumsub P,Kamchonwongpaisan S,Maneeruttanarungroj C,Nichols SE,Lyons TM,Tirado-Rives J,Jorgensen WL,Yuthavong Y,Anderson KS

    更新日期:2009-01-16 00:00:00

  • Characterization of Sviceucin from Streptomyces Provides Insight into Enzyme Exchangeability and Disulfide Bond Formation in Lasso Peptides.

    abstract::Lasso peptides are bacterial ribosomally synthesized and post-translationally modified peptides. They have sparked increasing interest in peptide-based drug development because of their compact, interlocked structure, which offers superior stability and protein-binding capacity. Disulfide bond-containing lasso peptide...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/acschembio.5b00584

    authors: Li Y,Ducasse R,Zirah S,Blond A,Goulard C,Lescop E,Giraud C,Hartke A,Guittet E,Pernodet JL,Rebuffat S

    更新日期:2015-11-20 00:00:00

  • Dark Hydrazone Fluorescence Labeling Agents Enable Imaging of Cellular Aldehydic Load.

    abstract::Aldehydes are key intermediates in many cellular processes, from endogenous metabolic pathways like glycolysis to undesired exogenously induced processes such as lipid peroxidation and DNA interstrand cross-linking. Alkyl aldehydes are well documented to be cytotoxic, affecting the functions of DNA and protein, and th...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/acschembio.6b00269

    authors: Yuen LH,Saxena NS,Park HS,Weinberg K,Kool ET

    更新日期:2016-08-19 00:00:00

  • Rational design, preparation, and characterization of a therapeutic enzyme mutant with improved stability and function for cocaine detoxification.

    abstract::Cocaine esterase (CocE) is known as the most efficient natural enzyme for cocaine hydrolysis. The major obstacle to the clinical application of wild-type CocE is the thermoinstability with a half-life of only ∼12 min at 37 °C. The previously designed T172R/G173Q mutant (denoted as enzyme E172-173) with an improved in ...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/cb500257s

    authors: Fang L,Chow KM,Hou S,Xue L,Chen X,Rodgers DW,Zheng F,Zhan CG

    更新日期:2014-08-15 00:00:00

  • Design and Application of a DNA-Encoded Macrocyclic Peptide Library.

    abstract::A DNA-encoded macrocyclic peptide library was designed and synthesized with 2.4 × 1012 members composed of 4-20 natural and non-natural amino acids. Affinity-based selection was performed against two therapeutic targets, VHL and RSV N protein. On the basis of selection data, some peptides were selected for resynthesis...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/acschembio.7b00852

    authors: Zhu Z,Shaginian A,Grady LC,O'Keeffe T,Shi XE,Davie CP,Simpson GL,Messer JA,Evindar G,Bream RN,Thansandote PP,Prentice NR,Mason AM,Pal S

    更新日期:2018-01-19 00:00:00

  • Gel electrophoresis and X-ray fluorescence: A powerful combination for the analysis of protein metal binding.

    abstract::Understanding the complex biochemical mechanisms that underlie the regulation, toxicity, and protein binding of metal ions requires the ability to analyze the metal content of individual proteins in complex mixtures. In this issue of ACS Chemical Biology, a technique combining gel electrophoresis with synchrotron X-ra...

    journal_title:ACS chemical biology

    pub_type: 评论,杂志文章

    doi:10.1021/cb100145z

    authors: Zahler NH

    更新日期:2010-06-18 00:00:00

  • Quantitative Chemical Proteomic Profiling of Ubiquitin Specific Proteases in Intact Cancer Cells.

    abstract::Deubiquitinating enzymes play an important role in a plethora of therapeutically relevant processes and are emerging as pioneering drug targets. Herein, we present a novel probe, Ubiquitin Specific Protease (USP) inhibitor, alongside an alkyne-tagged activity-based probe analogue. Activity-based proteome profiling ide...

    journal_title:ACS chemical biology

    pub_type: 信件

    doi:10.1021/acschembio.6b00766

    authors: Ward JA,McLellan L,Stockley M,Gibson KR,Whitlock GA,Knights C,Harrigan JA,Jacq X,Tate EW

    更新日期:2016-12-16 00:00:00

  • Functional and Structural Insights into a Novel Promiscuous Ketoreductase of the Lugdunomycin Biosynthetic Pathway.

    abstract::Angucyclines are a structurally diverse class of actinobacterial natural products defined by their varied polycyclic ring systems, which display a wide range of biological activities. We recently discovered lugdunomycin (1), a highly rearranged polyketide antibiotic derived from the angucycline backbone that is synthe...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/acschembio.0c00564

    authors: Xiao X,Elsayed SS,Wu C,van der Heul HU,Metsä-Ketelä M,Du C,Prota AE,Chen CC,Liu W,Guo RT,Abrahams JP,van Wezel GP

    更新日期:2020-09-18 00:00:00

  • Surprising Non-Additivity of Methyl Groups in Drug-Kinase Interaction.

    abstract::Drug optimization is guided by biophysical methods with increasing popularity. In the context of lead structure modifications, the introduction of methyl groups is a simple but potentially powerful approach. Hence, it is crucial to systematically investigate the influence of ligand methylation on biophysical character...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/acschembio.9b00476

    authors: Wienen-Schmidt B,Schmidt D,Gerber HD,Heine A,Gohlke H,Klebe G

    更新日期:2019-12-20 00:00:00

  • Deciphering the Cellular Targets of Bioactive Compounds Using a Chloroalkane Capture Tag.

    abstract::Phenotypic screening of compound libraries is a significant trend in drug discovery, yet success can be hindered by difficulties in identifying the underlying cellular targets. Current approaches rely on tethering bioactive compounds to a capture tag or surface to allow selective enrichment of interacting proteins for...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/acschembio.5b00351

    authors: Ohana RF,Kirkland TA,Woodroofe CC,Levin S,Uyeda HT,Otto P,Hurst R,Robers MB,Zimmerman K,Encell LP,Wood KV

    更新日期:2015-10-16 00:00:00

  • A Multimodal Ca(II) Responsive Near IR-MR Contrast Agent Exhibiting High Cellular Uptake.

    abstract::Ca(II) ions are critical for the proper function of neurons by contributing to synaptic signaling and regulating neuronal plasticity. Dysregulation of Ca(II) is associated with a number of pathologies that cause neurodegeneration; therefore the ability to monitor Ca(II) intracellularly is an important target for molec...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/acschembio.9b00638

    authors: Adams CJ,Krueger R,Meade TJ

    更新日期:2020-02-21 00:00:00

  • Rational Design of Hybrid Natural Products by Utilizing the Promiscuity of an Amide Synthetase.

    abstract::WS9326A and annimycin are produced by Streptomyces asterosporus DSM 41452. WS9326A is a nonribosomal peptide synthetase-(NRPS-) derived depsipeptide containing a cinnamoyl moiety, while annimycin is a linear polyketide bearing a 2-amino-3-hydroxycyclopent-2-enone (C5N) group. Both gene clusters have been sequenced and...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/acschembio.9b00351

    authors: Zhu J,Zhang S,Zechel DL,Paululat T,Bechthold A

    更新日期:2019-08-16 00:00:00

  • DprE1 Is a Vulnerable Tuberculosis Drug Target Due to Its Cell Wall Localization.

    abstract::The flavo-enzyme DprE1 catalyzes a key epimerization step in the decaprenyl-phosphoryl d-arabinose (DPA) pathway, which is essential for mycobacterial cell wall biogenesis and targeted by several new tuberculosis drug candidates. Here, using differential radiolabeling with DPA precursors and high-resolution fluorescen...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/acschembio.5b00237

    authors: Brecik M,Centárová I,Mukherjee R,Kolly GS,Huszár S,Bobovská A,Kilacsková E,Mokošová V,Svetlíková Z,Šarkan M,Neres J,Korduláková J,Cole ST,Mikušová K

    更新日期:2015-07-17 00:00:00

  • ANS binding reveals common features of cytotoxic amyloid species.

    abstract::Oligomeric assemblies formed from a variety of disease-associated peptides and proteins have been strongly associated with toxicity in many neurodegenerative conditions, such as Alzheimer's disease. The precise nature of the toxic agents, however, remains still to be established. We show that prefibrillar aggregates o...

    journal_title:ACS chemical biology

    pub_type: 信件

    doi:10.1021/cb1001203

    authors: Bolognesi B,Kumita JR,Barros TP,Esbjorner EK,Luheshi LM,Crowther DC,Wilson MR,Dobson CM,Favrin G,Yerbury JJ

    更新日期:2010-08-20 00:00:00

  • Recruitment and Regulation of the Non-ribosomal Peptide Synthetase Modifying Cytochrome P450 Involved in Nikkomycin Biosynthesis.

    abstract::The β-hydroxylation of l-histidine is the first step in the biosynthesis of the imidazolone base of the antifungal drug nikkomycin. The cytochrome P450 (NikQ) hydroxylates the amino acid while it is appended via a phosphopantetheine linker to the non-ribosomal peptide synthetase (NRPS) NikP1. The latter enzyme is comp...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/acschembio.7b00081

    authors: Wise CE,Makris TM

    更新日期:2017-05-19 00:00:00

  • Using small molecules and chemical genetics to interrogate signaling networks.

    abstract::The limited clinical success of therapeutics targeting cellular signaling processes is due to multiple factors, including off-target effects and complex feedback regulation encoded within the signaling network. To understand these effects, chemical proteomics and chemical genetics tools have been developed to map the ...

    journal_title:ACS chemical biology

    pub_type: 杂志文章,评审

    doi:10.1021/cb1002834

    authors: Carlson SM,White FM

    更新日期:2011-01-21 00:00:00

  • A Hydrogel-Microsphere Drug Delivery System That Supports Once-Monthly Administration of a GLP-1 Receptor Agonist.

    abstract::We have developed a chemically controlled very long-acting delivery system to support once-monthly administration of a peptidic GLP-1R agonist. Initially, the prototypical GLP-1R agonist exenatide was covalently attached to hydrogel microspheres by a self-cleaving β-eliminative linker; after subcutaneous injection in ...

    journal_title:ACS chemical biology

    pub_type: 杂志文章

    doi:10.1021/acschembio.7b00218

    authors: Schneider EL,Hearn BR,Pfaff SJ,Reid R,Parkes DG,Vrang N,Ashley GW,Santi DV

    更新日期:2017-08-18 00:00:00