Aminocoumarins: COUMARINS with an amino group, exemplified by NOVOBIOCIN.Architectural Accessibility: Designs for approaching areas inside or outside facilities.Anti-Bacterial Agents: Substances that reduce the growth or reproduction of BACTERIA.Mastodynia: Pain in the breast generally classified as cyclical (associated with menstrual periods), or noncyclical, i.e. originating from the breast or nearby muscles or joints, ranging from minor discomfort to severely incapacitating.Sesquiterpenes, Germacrane: SESQUITERPENES cyclized to one 10-carbon ring.Drug Resistance, Bacterial: The ability of bacteria to resist or to become tolerant to chemotherapeutic agents, antimicrobial agents, or antibiotics. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS).Drug Resistance, Microbial: The ability of microorganisms, especially bacteria, to resist or to become tolerant to chemotherapeutic agents, antimicrobial agents, or antibiotics. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS).Drug Utilization: The utilization of drugs as reported in individual hospital studies, FDA studies, marketing, or consumption, etc. This includes drug stockpiling, and patient drug profiles.Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials.LaunderingDetergents: Purifying or cleansing agents, usually salts of long-chain aliphatic bases or acids, that exert cleansing (oil-dissolving) and antimicrobial effects through a surface action that depends on possessing both hydrophilic and hydrophobic properties.Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties.Household Products: Substances or materials used in the course of housekeeping or personal routine.Carotenoids: The general name for a group of fat-soluble pigments found in green, yellow, and leafy vegetables, and yellow fruits. They are aliphatic hydrocarbons consisting of a polyisoprene backbone.Saturn: The sixth planet in order from the sun. It is one of the five outer planets of the solar system. Its twelve natural satellites include Phoebe and Titan.LacquerThermal Conductivity: The heat flow across a surface per unit area per unit time, divided by the negative of the rate of change of temperature with distance in a direction perpendicular to the surface. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Plastics: Polymeric materials (usually organic) of large molecular weight which can be shaped by flow. Plastic usually refers to the final product with fillers, plasticizers, pigments, and stabilizers included (versus the resin, the homogeneous polymeric starting material). (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)PrintingBody Temperature Regulation: The processes of heating and cooling that an organism uses to control its temperature.Convection: Transmission of energy or mass by a medium involving movement of the medium itself. The circulatory movement that occurs in a fluid at a nonuniform temperature owing to the variation of its density and the action of gravity. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed; Webster, 10th ed)Patents as Topic: Exclusive legal rights or privileges applied to inventions, plants, etc.Parabens: Methyl, propyl, butyl, and ethyl esters of p-hydroxybenzoic acid. They have been approved by the FDA as antimicrobial agents for foods and pharmaceuticals. (From Hawley's Condensed Chemical Dictionary, 11th ed, p872)Metabolic Engineering: Methods and techniques used to genetically modify cells' biosynthetic product output and develop conditions for growing the cells as BIOREACTORS.Netherlands: Country located in EUROPE. It is bordered by the NORTH SEA, BELGIUM, and GERMANY. Constituent areas are Aruba, Curacao, Sint Maarten, formerly included in the NETHERLANDS ANTILLES.Oxo-Acid-Lyases: Enzymes that catalyze the cleavage of a carbon-carbon bond of a 3-hydroxy acid. (Dorland, 28th ed) EC 4.1.3.Plants, Genetically Modified: PLANTS, or their progeny, whose GENOME has been altered by GENETIC ENGINEERING.Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc.Plant Proteins: Proteins found in plants (flowers, herbs, shrubs, trees, etc.). The concept does not include proteins found in vegetables for which VEGETABLE PROTEINS is available.Peptide Synthases: Ligases that catalyze the joining of adjacent AMINO ACIDS by the formation of carbon-nitrogen bonds between their carboxylic acid groups and amine groups.Polyketide Synthases: Large enzyme complexes composed of a number of component enzymes that are found in STREPTOMYCES which biosynthesize MACROLIDES and other polyketides.Peptide Biosynthesis, Nucleic Acid-Independent: The enzymatic synthesis of PEPTIDES without an RNA template by processes that do not use the ribosomal apparatus (RIBOSOMES).Polyketides: Natural compounds containing alternating carbonyl and methylene groups (beta-polyketones), bioenergenetically derived from repeated condensation of acetyl coenzyme A via malonyl coenzyme A, in a process similar to fatty acid synthesis.Multigene Family: A set of genes descended by duplication and variation from some ancestral gene. Such genes may be clustered together on the same chromosome or dispersed on different chromosomes. Examples of multigene families include those that encode the hemoglobins, immunoglobulins, histocompatibility antigens, actins, tubulins, keratins, collagens, heat shock proteins, salivary glue proteins, chorion proteins, cuticle proteins, yolk proteins, and phaseolins, as well as histones, ribosomal RNA, and transfer RNA genes. The latter three are examples of reiterated genes, where hundreds of identical genes are present in a tandem array. (King & Stanfield, A Dictionary of Genetics, 4th ed)Tyrocidine: An antibiotic mixture produced by Bacillus brevis which may be separated into three components, tyrocidines A, B, and C. It is the major constituent (40-60 per cent) of tyrothricin, gramicidin accounting for the remaining 10-20 per cent active material. It is a topical antimicrobial agent, that is very toxic parenterally.Streptomyces: A genus of bacteria that form a nonfragmented aerial mycelium. Many species have been identified with some being pathogenic. This genus is responsible for producing a majority of the ANTI-BACTERIAL AGENTS of practical value.Streptococcus pneumoniae: A gram-positive organism found in the upper respiratory tract, inflammatory exudates, and various body fluids of normal and/or diseased humans and, rarely, domestic animals.DNA Gyrase: A bacterial DNA topoisomerase II that catalyzes ATP-dependent breakage of both strands of DNA, passage of the unbroken strands through the breaks, and rejoining of the broken strands. Gyrase binds to DNA as a heterotetramer consisting of two A and two B subunits. In the presence of ATP, gyrase is able to convert the relaxed circular DNA duplex into a superhelix. In the absence of ATP, supercoiled DNA is relaxed by DNA gyrase.DNA, Superhelical: Circular duplex DNA isolated from viruses, bacteria and mitochondria in supercoiled or supertwisted form. This superhelical DNA is endowed with free energy. During transcription, the magnitude of RNA initiation is proportional to the DNA superhelicity.DNA Topoisomerases, Type II: DNA TOPOISOMERASES that catalyze ATP-dependent breakage of both strands of DNA, passage of the unbroken strands through the breaks, and rejoining of the broken strands. These enzymes bring about relaxation of the supercoiled DNA and resolution of a knotted circular DNA duplex.Novobiocin: An antibiotic compound derived from Streptomyces niveus. It has a chemical structure similar to coumarin. Novobiocin binds to DNA gyrase, and blocks adenosine triphosphatase (ATPase) activity. (From Reynolds, Martindale The Extra Pharmacopoeia, 30th ed, p189)Bacterial Proteins: Proteins found in any species of bacterium.DNA Topoisomerase IV: A bacterial DNA topoisomerase II that catalyzes ATP-dependent breakage of both strands of DNA, passage of the unbroken strands through the breaks, and rejoining of the broken strands. Topoisomerase IV binds to DNA as a heterotetramer consisting 2 parC and 2 parE subunits. Topoisomerase IV is a decatenating enzyme that resolves interlinked daughter chromosomes following DNA replication.Siloxanes: Silicon polymers that contain alternate silicon and oxygen atoms in linear or cyclic molecular structures.Dental Impression Materials: Substances used to create an impression, or negative reproduction, of the teeth and dental arches. These materials include dental plasters and cements, metallic oxide pastes, silicone base materials, or elastomeric materials.Dental Impression Technique: Procedure of producing an imprint or negative likeness of the teeth and/or edentulous areas. Impressions are made in plastic material which becomes hardened or set while in contact with the tissue. They are later filled with plaster of Paris or artificial stone to produce a facsimile of the oral structures present. Impressions may be made of a full complement of teeth, of areas where some teeth have been removed, or in a mouth from which all teeth have been extracted. (Illustrated Dictionary of Dentistry, 1982)Silicon Dioxide: Transparent, tasteless crystals found in nature as agate, amethyst, chalcedony, cristobalite, flint, sand, QUARTZ, and tridymite. The compound is insoluble in water or acids except hydrofluoric acid.Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., BIOPOLYMERS; PLASTICS).PolyvinylsShikimic Acid: A tri-hydroxy cyclohexene carboxylic acid important in biosynthesis of so many compounds that the shikimate pathway is named after it.Encyclopedias as Topic: Works containing information articles on subjects in every field of knowledge, usually arranged in alphabetical order, or a similar work limited to a special field or subject. (From The ALA Glossary of Library and Information Science, 1983)Imino Sugars: Sugars in which the OXYGEN is replaced by a NITROGEN atom. This substitution prevents normal METABOLISM resulting in inhibition of GLYCOSIDASES and GLYCOSYLTRANSFERASES.Prephenate Dehydratase: An enzyme that catalyzes the conversion of prephenate to phenylpyruvate with the elimination of water and carbon dioxide. In the enteric bacteria this enzyme also possesses chorismate mutase activity, thereby catalyzing the first two steps in the biosynthesis of phenylalanine. EC 4.2.1.51.

Novobiocin and related coumarins and depletion of heat shock protein 90-dependent signaling proteins. (1/101)

BACKGROUND: Heat shock protein 90 (Hsp90) interacts with and stabilizes several oncogenic protein kinases (e.g., p185(erbB2), p60(v-src), and Raf-1) and is required for the stability and dominant-negative function of mutated p53 protein. Two unrelated antibiotics, geldanamycin and radicicol, bind specifically to an atypical nucleotide-binding pocket of Hsp90, a site that shares homology with the adenosine triphosphate (ATP)-binding domain of bacterial DNA gyrase B. This interaction leads to destabilization of proteins that interact with Hsp90. Since the nucleotide-binding site of gyrase B is targeted by coumarin antibiotics (e.g., novobiocin), we investigated whether these drugs can also interact with Hsp90 and affect its activity. METHODS: We used immobilized novobiocin, geldanamycin, or radicicol to isolate either endogenous Hsp90 from cell lysates or Hsp90 deletion fragments translated in vitro. Effects of the coumarin antibiotics novobiocin, chlorobiocin, and coumermycin A1 on several proteins interacting with Hsp90 were assessed in vitro and in vivo. RESULTS: Hsp90 binding to immobilized novobiocin was competed by soluble coumarins and ATP but not by geldanamycin or radicicol. A carboxy-terminal Hsp90 fragment bound immobilized novobiocin but not immobilized geldanamycin, while a geldanamycin-binding amino-terminal fragment did not bind novobiocin. All three coumarins markedly reduced cellular levels of p185(erbB2), p60(v-src), Raf-1, and mutated p53. Furthermore, novobiocin reduced Raf-1 levels in the spleens of mice treated with the drug. CONCLUSIONS: These coumarin antibiotics, particularly novobiocin, represent a first-generation alternative to other Hsp90-targeting drugs that are not as well tolerated. Novobiocin's unique interaction with Hsp90 identifies an additional site on this protein amenable to pharmacologic interference with small molecules.  (+info)

Suppression of chromosome segregation defects of Escherichia coli muk mutants by mutations in topoisomerase I. (2/101)

Escherichia coli muk mutants are temperature-sensitive and produce anucleate cells. A spontaneously occurring mutation was found in a DeltamukBkan mutant strain that suppressed the temperature-sensitive phenotype and mapped in or near topA, the gene that encodes topoisomerase I. Previously characterized topA mutations, topA10 and topA66, were found to be general suppressors of muk mutants: they suppressed temperature sensitivity and anucleate cell production of cells containing null or point mutations in mukB and null mutations in mukE or mukF. The suppression correlated with excess negative supercoiling by DNA gyrase, and the gyrase inhibitor, coumermycin, reversed it. Defects in topA allow 99% of cell division events in muk null mutants to proceed without chromosome loss or loss of cell viability. This observation imposes important limitations on models for Muk activity and is consistent with a role for MukBEF in chromosome folding and DNA condensation.  (+info)

Membrane localization of Raf assists engagement of downstream effectors. (3/101)

We have previously described a small molecule-directed protein dimerization strategy, using coumermycin to juxtapose Raf fusion proteins containing the coumermycin-binding domain GyrB. Oligomerization of cytoplasmically localized Raf-GyrB fusion proteins leads to an increase in the kinase activity of both Raf and its substrate Mek. Surprisingly, more distal targets, such as Erk1 and Erk2, are not activated using this approach. Here we report that coumermycin-induced oligomerization of a membrane-localized Raf-GyrB fusion protein potently activated Erk1 and Erk2, up-regulated Fos protein levels, and induced expression of many immediate-early response genes. Thus, both membrane localization and oligomerization of Raf-GyrB are required to target Raf signals to downstream effectors. The ability to activate the entire Raf signal transduction cascade conditionally, using coumermycin-induced oligomerization, should prove useful for dissecting Raf-mediated effects on gene expression and cellular differentiation.  (+info)

Identification of the coumermycin A(1) biosynthetic gene cluster of Streptomyces rishiriensis DSM 40489. (4/101)

The biosynthetic gene cluster of the aminocoumarin antibiotic coumermycin A(1) was cloned by screening of a cosmid library of Streptomyces rishiriensis DSM 40489 with heterologous probes from a dTDP-glucose 4,6-dehydratase gene, involved in deoxysugar biosynthesis, and from the aminocoumarin resistance gyrase gene gyrB(r). Sequence analysis of a 30.8-kb region upstream of gyrB(r) revealed the presence of 28 complete open reading frames (ORFs). Fifteen of the identified ORFs showed, on average, 84% identity to corresponding ORFs in the biosynthetic gene cluster of novobiocin, another aminocoumarin antibiotic. Possible functions of 17 ORFs in the biosynthesis of coumermycin A(1) could be assigned by comparison with sequences in GenBank. Experimental proof for the function of the identified gene cluster was provided by an insertional gene inactivation experiment, which resulted in an abolishment of coumermycin A(1) production.  (+info)

Chimeric VEGFRs are activated by a small-molecule dimerizer and mediate downstream signalling cascades in endothelial cells. (5/101)

Despite much interest in vascular endothelial growth factor (VEGF) and its receptors (VEGFRs -1 and -2), VEGF-induced signalling cascades remain incompletely defined. Attempts to assign individual responses to a particular receptor have used either transfected cell lines, receptor-specific growth factors or antisense oligonucleotides. Such studies have attributed the majority of VEGF-induced responses to activation of VEGFR-2. As a consequence of poor growth factor-induced VEGFR-1 autophosphorylation however, observations from these studies may instead reflect the relative activation of the two receptors. We have generated novel chimeric VEGF receptors in which the dimerization domain of the B subunit of DNA gyrase is fused to the cytoplasmic domain of VEGFRs -1 and -2. When expressed in porcine aortic endothelial cells, both chimeric VEGFR-1 and -2 autophosphorylate in response to addition of the small-molecule dimerizing agent, coumermycin. Once activated, both receptors induce downstream signalling cascades, exemplified here by the activation of MAPK, PLCgamma and PKB/Akt. Furthermore, we demonstrate that the Y1175 residue of VEGFR-2 is essential for the activation of PLCgamma mediated by this chimeric receptor. In contrast to previous reports which show a limited ability of VEGFR-1 to mediate signalling cascades, we show that once sufficiently activated, VEGFR-1 signals in a similar manner to VEGFR-2 in endothelial cells.  (+info)

Brachyspira (Serpulina) hyodysenteriae gyrB mutants and interstrain transfer of coumermycin A(1) resistance. (6/101)

To further develop genetic techniques for the enteropathogen Brachyspira hyodysenteriae, the gyrB gene of this spirochete was isolated from a lambdaZAPII library of strain B204 genomic DNA and sequenced. The putative protein encoded by this gene exhibited up to 55% amino acid sequence identity with GyrB proteins of various bacterial species, including other spirochetes. B. hyodysenteriae coumermycin A(1)-resistant (Cn(r)) mutant strains, both spontaneous and UV induced, were isolated by plating B204 cells onto Trypticase soy blood agar plates containing 0.5 microg of coumermycin A(1)/ml. The coumermycin A(1) MICs were 25 to 100 microg/ml for the resistant strains and 0.1 to 0.25 microg/ml for strain B204. Four Cn(r) strains had single nucleotide changes in their gyrB genes, corresponding to GyrB amino acid changes of Gly(78) to Ser (two strains), Gly(78) to Cys, and Thr(166) to Ala. When Cn(r) strain 435A (Gly(78) to Ser) and Cm(r) Km(r) strain SH (DeltaflaA1::cat Deltanox::kan) were cultured together in brain heart infusion broth containing 10% (vol/vol) heat-treated (56 degrees C, 30 min) calf serum, cells resistant to chloramphenicol, coumermycin A(1), and kanamycin could be isolated from the cocultures after overnight incubation, but such cells could not be isolated from monocultures of either strain. Seven Cn(r) Km(r) Cm(r) strains were tested and were determined to have resistance genotypes of both strain 435A and strain SH. Cn(r) Km(r) Cm(r) cells could not be isolated when antiserum to the bacteriophage-like agent VSH-1 was added to cocultures, and the numbers of resistant cells increased fivefold when mitomycin C, an inducer of VSH-1 production, was added. These results indicate that coumermycin resistance associated with a gyrB mutation is a useful selection marker for monitoring gene exchange between B. hyodysenteriae cells. Gene transfer readily occurs between B. hyodysenteriae cells in broth culture, a finding with practical importance. VSH-1 is the likely mechanism for gene transfer.  (+info)

Complementation of a Treponema denticola flgE mutant with a novel coumermycin A1-resistant T. denticola shuttle vector system. (7/101)

By using the mutated gyrB gene from a spontaneous coumermycin A1-resistant Treponema denticola, an Escherichia coli-T. denticola shuttle vector that renders T. denticola resistant to coumermycin was constructed. The complete T. denticola flgE gene was cloned into the shuttle vector pKMCou, and the vector was transformed into the T. denticola ATCC 33520 flgE erythromycin-resistant knockout mutant HL210. The coumermycin-resistant transformants were motile and restored FlgE activity. This complementation system should prove useful in studying the virulence factors of T. denticola and uncultivatible pathogenic spirochetes.  (+info)

Promoter protection by a transcription factor acting as a local topological homeostat. (8/101)

Binding of the Escherichia coli global transcription factor FIS to the upstream activating sequence (UAS) of stable RNA promoters activates transcription on the outgrowth of cells from stationary phase. Paradoxically, while these promoters require negative supercoiling of DNA for optimal activity, FIS counteracts the increase of negative superhelical density by DNA gyrase. We demonstrate that binding of FIS at the UAS protects the rrnA P1 promoter from inactivation at suboptimal superhelical densities. This effect is correlated with FIS-dependent constraint of writhe and facilitated untwisting of promoter DNA. We infer that FIS maintains stable RNA transcription by stabilizing local writhe in the UAS. These results suggest a novel mechanism of transcriptional regulation by a transcription factor acting as a local topological homeostat.  (+info)

Interactions of several 7-aminocoumarins with human serum albumin (HSA) were studied by using fluorescence spectroscopic technique and modeling studies. There is a large change in fluorescence spectral parameters like intensity, emission maxima and anisotropy for all aminocoumarins. There were two binding sites for cou-1, 311 and a single binding site for other coumarins. The binding constant(s) are large for all coumarins reflective of a strong binding. These spectral studies show that structural variants at the third, fourth and seventh position affects binding. The probable location of these coumarins in domain Ii has been predicted based on modeling. The effect of structural modification on the efficiency of binding was obtained for various other coumarins, using modeling.. ...
The 5-methyl-2-pyrrolylcarbonyl moiety of the aminocoumarin antibiotics clorobiocin and coumermycin A1 is the key pharmacophore for targeting the ATP-binding site of GyrB for inhibition of the bacterial type-II topoisomerase DNA gyrase. During the late stage of clorobiocin and coumermycin A1 biosynthesis, the pyrrolyl-2-carboxyl group is transferred from the peptidyl carrier proteins Clo/CouN1 to the 3-hydroxyl of the 4-methoxy-L-noviosyl scaffold by the action of the acyltransferases Clo/CouN7. CouN1 and CouN7 have now been heterologously expressed and purified from Escherichia coli. The apo form of CouN1 is converted to the acyl-holo form by loading with pyrrolyl-2-carboxyl-S-pantetheinyl moieties from synthetic pyrrolyl- and 5-methylpyrrolyl-CoAs by the action of the phosphopantetheinyl transferase Sfp. CouN7 acts as an acyltransferase, moving the pyrrole acyl moieties from CouN1 to the noviose sugar of descarbamoylnovobiocin. When the 5-methylpyrrolyl-2-carboxyl-thioester of CouN1 is the
16907743] The small MbtH-like protein encoded by an internal gene of the balhimycin biosynthetic gene cluster is not required for glycopeptide production. (FEMS Microbiol Lett. , 2006 ...
This aminocoumarin antibiotic consists of three major substituents. The 3-dimethylallyl-4-hydroxybenzoic acid moiety, known as ring A, is derived from prephenate and dimethylallyl pyrophosphate. The aminocoumarin moiety, known as ring B, is derived from L-tyrosine. The final component of novobiocin is the sugar derivative L-noviose, known as ring C, which is derived from glucose-1-phosphate. The biosynthetic gene cluster for novobiocin was identified by Heide and coworkers in 1999 (published 2000) from Streptomyces spheroides NCIB 11891.[18] They identified 23 putative open reading frames (ORFs) and more than 11 other ORFs that may play a role in novobiocin biosynthesis. The biosynthesis of ring A (see Fig. 1) begins with prephenate which is a derived from the shikimic acid biosynthetic pathway. The enzyme NovF catalyzes the decarboxylation of prephenate while simultaneously reducing nicotinamide adenine dinucleotide phosphate (NADP+) to produce NADPH. Following this NovQ catalyzes the ...
ID V6KJ36_STRRC Unreviewed; 572 AA. AC V6KJ36; DT 19-FEB-2014, integrated into UniProtKB/TrEMBL. DT 19-FEB-2014, sequence version 1. DT 22-NOV-2017, entry version 21. DE SubName: Full=Chitinase {ECO:0000313,EMBL:EST32170.1}; GN ORFNames=M878_15530 {ECO:0000313,EMBL:EST32170.1}; OS Streptomyces roseochromogenus subsp. oscitans DS 12.976. OC Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae; OC Streptomyces. OX NCBI_TaxID=1352936 {ECO:0000313,EMBL:EST32170.1, ECO:0000313,Proteomes:UP000017984}; RN [1] {ECO:0000313,EMBL:EST32170.1, ECO:0000313,Proteomes:UP000017984} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=DS 12.976 {ECO:0000313,EMBL:EST32170.1}; RX PubMed=24407645; RA Ruckert C., Kalinowski J., Heide L., Apel A.K.; RT "Draft Genome Sequence of Streptomyces roseochromogenes subsp. RT oscitans DS 12.976, Producer of the Aminocoumarin Antibiotic RT Clorobiocin."; RL Genome Announc. 2:e01147-13(2014). CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 18 family. CC ...
The pF12K RM Flexi® Vector is part of the Flexi® Vector System and a component of the Regulated Mammalian Expression System (Cat. C9470). High levels of expression can be achieved upon induction with coumermycin. All Flexi® vectors carry the lethal barnase gene, which is replaced by the DNA fragment of interest and acts as a positive selection for successful ligation of the insert. This vector provides kanamycin resistance in |em>E. coli|/em>.
Inhibits the supercoiling activity of DNA gyrase. Acts by inhibiting DNA gyrase at an early step, prior to (or at the step of) binding of DNA by the gyrase. It protects cells against toxins that target DNA gyrase, by inhibiting activity of these toxins and reducing the formation of lethal double-strand breaks in the cell. Protects cells against the natural plasmid-encoded toxins microcin B17 (MccB17) and CcdB, and synthetic quinolones. Can also protect cells against alkylating agents that act independently of DNA gyrase, suggesting a more general role in protecting cells against DNA damage.
A 990581 was a 2-pyridone novel DNA gyrase inhibitor with potent activity against both Gram-positive and Gram-negative resistant bacteria including anaerobes.
The role of MbtH-like proteins in nonribosomal peptides synthetase (NRPS) assembly-lines: Tools for biosynthesis/bioengineering of novel antibiotics.
Hi Ronan, for pBR322 I use 1 to 15 ug/ml chloroquin in gel and running buffer. Topoisomers of pBR isolated from E. coli are clearly separated at 10 ug/ml chloroquin, except when the DNA is extremely relaxed (like when you add a gyrase inhibitor), then you need to add less chloroquin. Extremely supercoiled DNA needs more chloroquin to pull the bands apart. but not too much, or youll get positively writhed plasmids on top of the negative ones. Good luck, Rogier * Sent from RemarQ http://www.remarq.com The Internets Discussion Network * The fastest and easiest way to search and participate in Usenet - Free ...
Glycosylated analogues of novobiocin, discovered using a broad library of enzymes, have 100-fold improved activity against breast, brain, pancreatic, lung and ovarian cancers and ablated associated off-target activity leading to an up to 2.7 × 10(4) fold increase in selectivity.. ...
The MSRRTC is funded by the U.S. Department of Education, National Institute for Disability and Rehabilitation Research under cooperative agreement H133B080025, from 2008-2013. The information developed by the MSRRTC does not necessarily represent the policy of the Department of Education, and you should not assume endorsement by the Federal Government (Edgar, 75.620 (b)). ...
4GGL: Pyrrolopyrimidine inhibitors of dna gyrase b and topoisomerase iv, part i: structure guided discovery and optimization of dual targeting agents with potent, broad-spectrum enzymatic activity
4HYM: Pyrrolopyrimidine inhibitors of DNA gyrase B (GyrB) and topoisomerase IV (ParE). Part I: Structure guided discovery and optimization of dual targeting agents with potent, broad-spectrum enzymatic activity.
DNA gyrase is a bacterial enzyme that catalyzes the ATP-dependent negative supercoiling of double-stranded, closed-circular DNA, according to the Critical Review of Biochemical and Molecular Biology....
Definition of DNA reverse gyrase with photos and pictures, translations, sample usage, and additional links for more information.
CL-promoted DNA cleavage mediated by gyrase occurs at specific sites and is stimulated by ATP. The 290-bp S fragment (from the S. pneumoniae parE gene) 33P-labe
Novobiocin binds to DNA gyrase and blocks adenosine triphosphatase (ATPase) activity. Novobiocin sodium is an antibiotic compound derived from Streptomyces nive ...
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Looking for online definition of DNA gyrase in the Medical Dictionary? DNA gyrase explanation free. What is DNA gyrase? Meaning of DNA gyrase medical term. What does DNA gyrase mean?
We have analysed the DNA cleavage reaction of DNA gyrase using oligonucleotides annealed to a singlestranded M13 derivative containing a preferred gyrase cleavage site. We find that gyrase can cleave duplexes down to ∼20 bp in size in the presence of the quinolone drugs ciprofloxacin and oxolinic acid. Ciprofloxacin shows a variation in its site specificity with an apparent preference for G bases adjacent to the cleavage sites, whereas oxolinic acid stimulates cleavage predominantly at the previously determined site. With either drug, cleavage will not occur within 6 bases from the end of a DNA duplex or a nick. We suggest that cleavage site specificity with short DNA duplexes is determined by drug-DNA interactions whereas with longer fragments the positioning effect of the DNA wrap around gyrase prescribes the site of cleavage ...
Infections caused by more than one type of organisms are called as mixed infections and the best therapeutic option for their treatment is to combine two different drugs with different mechanism of action. O2 is a combination of ofloxacin and ornidazole. Ofloxacin is second generation fluoro-quinolone antibiotic which inhibits bacterial DNA gyrase enzyme, interfering in the synthesis of DNA in the bacteria and shows bactericidal action. Ornidazole is a newer nitroimidazoles with superior efficacy and longer duration of action. It kills susceptible microorganisms by interfering with DNA functioning. Hence combination of these two drugs shown higher efficacy, broad antimicrobial spectrum, least incidence of side effects and both are well tolerated ...
DNA gyrase is involved in DNA replication, which happens when bacteria reproduce. A family of antibiotics called fluoroquinolones target this enzyme, killing the bacteria that cause infections such as cholera, anthrax, gonorrhoea, meningitis, E. coli and MRSA. The researchers found that when MurI binds to DNA gyrase, it takes gyrase away from substrate DNA. Because of this, antibiotics cannot bind and stop it from working, so the bacteria become resistant to treatment.. "Our findings suggest that MurI has a role in safeguarding DNA gyrase from attack by antibiotics," said Professor Nagaraja. "The moonlighting activity of MurI seems to have evolved more recently to protect and control DNA gyrase.". MurI is not alone in its moonlighting activities; other bacterial enzymes and proteins also carry out different functions. But why has this ability evolved? "Multifunctional proteins are mostly common enzymes that have acquired different roles over the long period of their existence," said Professor ...
"Genetic engineering of antibiotic biosynthesis for the generation of new aminocoumarins". Biotechnology Advances. 27 (6): 1006- ...
Heide, L. (2009). "Genetic engineering of antibiotic biosynthesis for the generation of new aminocoumarins". Biotechnology ...
Two classes of antibiotics that inhibit gyrase are: The aminocoumarins (including novobiocin). Aminocoumarins work by ...
Aminocoumarins are very potent inhibitors of bacterial DNA gyrase and work by targeting the GyrB subunit of the enzyme involved ... The overlap of the coumarin and ATP-binding sites is consistent with aminocoumarins being competitive inhibitors of the ATPase ...
... aminocoumarins MeSH D03.438.150.446.139.500 --- novobiocin MeSH D03.438.150.446.280 --- chromonar MeSH D03.438.150.446.350 --- ... aminocoumarins MeSH D03.830.219.446.139.500 --- novobiocin MeSH D03.830.219.446.280 --- chromonar MeSH D03.830.219.446.350 --- ...
... is a low cost drug.[7] In the United States, Salix Pharmaceuticals holds a US Patent for rifaximin and markets the drug under the name Xifaxan.[17][18] In addition to receiving FDA approval for traveler's diarrhea and (marketing approved for)[18] hepatic encephalopathy, rifaximin received FDA approval for IBS in May 2015.[19] No generic formulation is available in the US and none has appeared due to the fact that the FDA approval process was ongoing. If rifaximin receives full FDA approval for hepatic encephalopathy it is likely that Salix will maintain marketing exclusivity and be protected from generic formulations until March 24, 2017.[18] Rifaximin is approved in 33 countries for GI disorders.[20][21] On August 13, 2013, Health Canada issued a Notice of Compliance to Salix Pharmaceuticals Inc. for the drug product Zaxine.[22] In India it is available under the brand names Ciboz and Xifapill.[citation needed] In Russia and Ukraine the drug is sold under the name Alfa Normix ...
Although not formally a quinolone, nalidixic acid is considered the first quinolone drug. It was introduced in 1962 for treatment of urinary tract infections in humans.[70] Nalidixic acid was discovered by George Lesher and coworkers in a distillate during an attempt at chloroquine synthesis.[71] Nalidixic acid is thus considered to be the predecessor of all members of the quinolone family, including the second, third and fourth generations commonly known as fluoroquinolones. Since the introduction of nalidixic acid in 1962, more than 10,000 analogs have been synthesized, but only a handful have found their way into clinical practice. The first generation also included other quinolone drugs, such as pipemidic acid, oxolinic acid, and cinoxacin, which were introduced in the 1970s. They proved to be only marginal improvements over nalidixic acid.[72] These drugs were widely used as a first line treatment for many infections, including very commons ones like acute sinusitis, acute bronchitis, and ...
In a review of 2081 adult patients participating in a Phase III clinical trial of sparfloxacin in community-acquired, lower respiratory tract infections, sparfloxacin (200 or 400 mg loading dose then 100 or 200 mg daily; i.e. 200/100 mg and 400/200 mg) had a similar incidence of adverse events as the comparator agents (Rubinstein, 1996). The overall rates of drug-related adverse reactions for sparfloxacin 400/200 mg versus comparators and 200/100 mg versus the comparator (amoxicillin/clavulanic acid) were 13.7 versus 17.7%, and 9.5 versus 13.2%, respectively. However, many of these reported reactions were very minor; discontinua- tion of the antibacterial agent because of drug-related adverse reactions occurred in 1.6 versus 1.6%, and 1) versus 1.1%, respectively. Adverse reactions affecting the nervous system were reported in 5.7% of the sparfloxacin group, with insomnia and other sleep disorders the most common events ...
... is used to treat a wide variety of infections, including infections of bones and joints, endocarditis, gastroenteritis, malignant otitis externa, respiratory tract infections, cellulitis, urinary tract infections, prostatitis, anthrax, and chancroid.[2]. Ciprofloxacin only treats bacterial infections; it does not treat viral infections such as the common cold. For certain uses including acute sinusitis, lower respiratory tract infections and uncomplicated gonorrhea, ciprofloxacin is not considered a first-line agent.. Ciprofloxacin occupies an important role in treatment guidelines issued by major medical societies for the treatment of serious infections, especially those likely to be caused by Gram-negative bacteria, including Pseudomonas aeruginosa. For example, ciprofloxacin in combination with metronidazole is one of several first-line antibiotic regimens recommended by the Infectious Diseases Society of America for the treatment of community-acquired abdominal infections in ...
Photochemical reactions of 7-aminocoumarins. 10. Reaction of 3-iodo-4-methyl-7-diethylaminocoumarin with heteroaromatic ... and benzimidazole results in the formation of a series of 3-hetaryl-7-aminocoumarins. The spectral luminescence characteristics ...
Glycosylated Aminocoumarins And Methods Of Preparing And Uses Of Same. * Published: Oct 17, 2013 ...
We showed that the aminocoumarins profoundly prevent the structural changes caused by D-glucose, keeping the protein molecule ... Background: Synthesized aminocoumarins are heterocyclic compounds possessing potential for the treatment of insulin-dependent ...
... by Freda ... Complex Enzymes In Microbial Natural Product Biosynthesis Part B Polyketides Aminocoumarins And Carbohydrates 2009. Mickey ... Alongside David works his complex enzymes in microbial natural product biosynthesis part b polyketides aminocoumarins and ... Responding a complex enzymes in microbial natural product biosynthesis part b polyketides aminocoumarins problem AND BOOK ...
Antimicrobial class: Aminocoumarins, Glycolipids, Quinoxalines combined; Annual totals (kilograms of active ingredient): ...
... and the y-amino- coumarins. Specific examples of these brighteners include 4-methyl-7-diethylamino coumarin; l,2-bis(- ...
2lkyl-7dialkyl-amino coumarins, benzidine sulfone disulfonic acid, diphenyl pyrazoline. Any of these compounds are known and ... Also, the triazines, the diazines, the imidazoles, the oxazoles, the coumarins, the aminocoumarins, the sulfone sulfonic acids ...
By modifying aminocoumarins, the researchers said they hope to develop more effective inhibitors, turning them into more potent ... Aminocoumarins are inhibitors of bacterial enzymes that untwist and unknot DNA. Without these enzymes, bacteria cannot ... The researchers said they can generate potentially hundreds of variants of antibiotics called aminocoumarins. ...
"Genetic engineering of antibiotic biosynthesis for the generation of new aminocoumarins". Biotechnology Advances. 27 (6): 1006- ...
Heide, L. (2009). "Genetic engineering of antibiotic biosynthesis for the generation of new aminocoumarins". Biotechnology ...
Complex Enzymes in Microbial Natural Product Biosynthesis, Part B: Polyketides, Aminocoumarins and Carbohydr Academic Press ...
Saleh O, Haagen Y, Seeger K, Heide L (2009) Prenyl transfer to aromatic substrates in the biosynthesis of aminocoumarins, ... Li S-M, Heide L (2004) Functional analysis of biosynthetic genes of aminocoumarins and production of hybrid antibiotics; Curr ... Heide L (2009) Genetic engineering of antibiotic biosynthesis for the generation of new aminocoumarins. Biotechnol Adv 27: 1006 ... Heide L (2009) Aminocoumarins: Mutasynthesis, chemoenzymatic synthesis and metabolic engineering. Meth Enzymol. 459: 437-455 ...
... and the aminocoumarins. Specific examples of these brighteners include 4-methyl-7-diethyl- amino coumarin; 1,2-bis(- ...
... and the aminocoumarins. 这些增白剂的具体例子包括:4-甲基-7-二乙氨基香豆素;1,2-二(-venz咪唑-2-基)亚乙基;1,3-二苯基-环戊四唑啉(phrazoline);2,5-二
Various groups, e.g., aminocoumarins, carbapenems, cephalosporins, glycopeptides, macrolides, penicillins, quinolones/ ...
Organic dyes (fluorescein, rhodamine, N-aminocoumarins and derivatives of these). *Rare earth elements (lanthanides) ...
Cox, R.J.; Simpson, T.J. Complex enzymes in microbial natural product biosynthesis, part B: Polyketides, aminocoumarins and ...
2014). Altering gene expression by aminocoumarins: the role of DNA supercoiling in Staphylococcus aureus. BMC Genomics 15:291. ...
Also suitable are substituted aminocoumarins, for example, the 4-methyl-7-dimethyl-amino or the 4-methyl-7-diethylaminocoumarin ...
Aminocoumarins are very potent inhibitors of bacterial DNA gyrase and work by targeting the GyrB subunit of the enzyme involved ... The overlap of the coumarin and ATP-binding sites is consistent with aminocoumarins being competitive inhibitors of the ATPase ...
Other suitable polyamide brighteners are substituted aminocoumarins, for example 4-methyl-7-dimethylamino or 4-methyl-7- ...
Coumabiocins A-F, aminocoumarins from an organic extract of Streptomyces sp. L-4-4. ... led to the isolation of six new aminocoumarins, coumabiocins A-F (1-6), along with two known compounds, novobiocin (7) and ...
Saleh, O.; Haagen, Y.; Seeger, K.; Heide, L. Prenyl transfer to aromatic substrates in the biosynthesis of aminocoumarins, ...
The polyamide brighteners further include aliphatically or aromatically substituted aminocoumarins, such as 4-methyl-7- ...
Silica supported molybdic acid Azo coumarin dyes 7-Amino coumarins Phenol derivatives Efficient protocol ...
  • Fluoroquinolones (the DNA complex) and aminocoumarins (the ATP site) target these enzymes. (blogspot.com)
  • The overlap of the coumarin and ATP-binding sites is consistent with aminocoumarins being competitive inhibitors of the ATPase activity. (wikipedia.org)
  • Gyrase can be a proven medication target that may either become changed into a poison by little substances (e.g. fluoroquinolones) that stabilize the DNA cleavage condition, or end up being catalytically inhibited by various other little molecules (e.g. aminocoumarins) that inhibit the ATPase response and stop strand passing (15,16). (biodigestor.net)