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 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)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.Topoisomerase II Inhibitors: Compounds that inhibit the activity of DNA TOPOISOMERASE II. Included in this category are a variety of ANTINEOPLASTIC AGENTS which target the eukaryotic form of topoisomerase II and ANTIBACTERIAL AGENTS which target the prokaryotic form of topoisomerase II.Aminocoumarins: COUMARINS with an amino group, exemplified by NOVOBIOCIN.Oxolinic Acid: Synthetic antimicrobial related to NALIDIXIC ACID and used in URINARY TRACT INFECTIONS.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.Coumarins: Synthetic or naturally occurring substances related to coumarin, the delta-lactone of coumarinic acid.4-Quinolones: QUINOLONES containing a 4-oxo (a carbonyl in the para position to the nitrogen). They inhibit the A subunit of DNA GYRASE and are used as antimicrobials. Second generation 4-quinolones are also substituted with a 1-piperazinyl group at the 7-position and a fluorine at the 6-position.Fluoroquinolones: A group of QUINOLONES with at least one fluorine atom and a piperazinyl group.Quinolones: A group of derivatives of naphthyridine carboxylic acid, quinoline carboxylic acid, or NALIDIXIC ACID.Nalidixic Acid: A synthetic 1,8-naphthyridine antimicrobial agent with a limited bacteriocidal spectrum. It is an inhibitor of the A subunit of bacterial DNA GYRASE.Escherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.Anti-Infective Agents: Substances that prevent infectious agents or organisms from spreading or kill infectious agents in order to prevent the spread of infection.DNA, Bacterial: Deoxyribonucleic acid that makes up the genetic material of bacteria.DNA Topoisomerases, Type I: DNA TOPOISOMERASES that catalyze ATP-independent breakage of one of the two strands of DNA, passage of the unbroken strand through the break, and rejoining of the broken strand. DNA Topoisomerases, Type I enzymes reduce the topological stress in the DNA structure by relaxing the superhelical turns and knotted rings in the DNA helix.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).Norfloxacin: A synthetic fluoroquinolone (FLUOROQUINOLONES) with broad-spectrum antibacterial activity against most gram-negative and gram-positive bacteria. Norfloxacin inhibits bacterial DNA GYRASE.Ciprofloxacin: A broad-spectrum antimicrobial carboxyfluoroquinoline.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).Microbial Sensitivity Tests: Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses).Plasmids: Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.Anti-Bacterial Agents: Substances that reduce the growth or reproduction of BACTERIA.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Ofloxacin: A synthetic fluoroquinolone antibacterial agent that inhibits the supercoiling activity of bacterial DNA GYRASE, halting DNA REPLICATION.Bacterial Proteins: Proteins found in any species of bacterium.Enoxacin: A broad-spectrum 6-fluoronaphthyridinone antibacterial agent that is structurally related to NALIDIXIC ACID.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Genes, Bacterial: The functional hereditary units of BACTERIA.DNA, Catenated: CIRCULAR DNA that is interlaced together as links in a chain. It is used as an assay for the activity of DNA TOPOISOMERASES. Catenated DNA is attached loop to loop in contrast to CONCATENATED DNA which is attached end to end.NaphthyridinesTopoisomerase Inhibitors: Compounds that inhibit the activity of DNA TOPOISOMERASES.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.DNA Topoisomerases: Enzymes that regulate the topology of DNA by actions such as breaking, relaxing, passing, and rejoining strands of DNA in cells. These enzymes are important components of the DNA replication system. They are classified by their substrate specificities. DNA TOPOISOMERASE I enzymes act on a single strand of DNA. DNA TOPOISOMERASE II enzymes act on double strands of DNA.Pefloxacin: A synthetic broad-spectrum fluoroquinolone antibacterial agent active against most gram-negative and gram-positive bacteria.Adenylyl Imidodiphosphate: 5'-Adenylic acid, monoanhydride with imidodiphosphoric acid. An analog of ATP, in which the oxygen atom bridging the beta to the gamma phosphate is replaced by a nitrogen atom. It is a potent competitive inhibitor of soluble and membrane-bound mitochondrial ATPase and also inhibits ATP-dependent reactions of oxidative phosphorylation.Mycobacterium smegmatis: A rapid-growing, nonphotochromogenic species of MYCOBACTERIUM originally isolated from human smegma and found also in soil and water. (From Dorland, 28th ed)Levofloxacin: The L-isomer of Ofloxacin.Staphylococcus aureus: Potentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Adenosine Triphosphatases: A group of enzymes which catalyze the hydrolysis of ATP. The hydrolysis reaction is usually coupled with another function such as transporting Ca(2+) across a membrane. These enzymes may be dependent on Ca(2+), Mg(2+), anions, H+, or DNA.Micrococcus: A genus of gram-positive, spherical bacteria found in soils and fresh water, and frequently on the skin of man and other animals.Nucleic Acid Conformation: The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape.Adenosine Triphosphate: An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.Bacteriophage mu: A temperate coliphage, in the genus Mu-like viruses, family MYOVIRIDAE, composed of a linear, double-stranded molecule of DNA, which is able to insert itself randomly at any point on the host chromosome. It frequently causes a mutation by interrupting the continuity of the bacterial OPERON at the site of insertion.Mycoplasma hominis: A common inhabitant of the vagina and cervix and a potential human pathogen, causing infections of the male and female reproductive tracts. It has also been associated with respiratory disease and pharyngitis. (From Dorland, 28th ed)DNA Replication: The process by which a DNA molecule is duplicated.Topoisomerase I Inhibitors: Compounds that inhibit the activity of DNA TOPOISOMERASE I.Hexylresorcinol: A substituted dihydroxybenzene used topically as an antiseptic for the treatment of minor skin infections.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.Methylophilaceae: A family of gram-negative bacteria in the order Methylophilales.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Escherichia coli Proteins: Proteins obtained from ESCHERICHIA COLI.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.QuinolinesDNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Bacteriocins: Substances elaborated by specific strains of bacteria that are lethal against other strains of the same or related species. They are protein or lipopolysaccharide-protein complexes used in taxonomy studies of bacteria.Inhibitory Concentration 50: The concentration of a compound needed to reduce population growth of organisms, including eukaryotic cells, by 50% in vitro. Though often expressed to denote in vitro antibacterial activity, it is also used as a benchmark for cytotoxicity to eukaryotic cells in culture.Chromosomes, Bacterial: Structures within the nucleus of bacterial cells consisting of or containing DNA, which carry genetic information essential to the cell.DNA, Circular: Any of the covalently closed DNA molecules found in bacteria, many viruses, mitochondria, plastids, and plasmids. Small, polydisperse circular DNA's have also been observed in a number of eukaryotic organisms and are suggested to have homology with chromosomal DNA and the capacity to be inserted into, and excised from, chromosomal DNA. It is a fragment of DNA formed by a process of looping out and deletion, containing a constant region of the mu heavy chain and the 3'-part of the mu switch region. Circular DNA is a normal product of rearrangement among gene segments encoding the variable regions of immunoglobulin light and heavy chains, as well as the T-cell receptor. (Riger et al., Glossary of Genetics, 5th ed & Segen, Dictionary of Modern Medicine, 1992)Xanthomonas: A genus in the family XANTHOMONADACEAE whose cells produce a yellow pigment (Gr. xanthos - yellow). It is pathogenic to plants.F Factor: A plasmid whose presence in the cell, either extrachromosomal or integrated into the BACTERIAL CHROMOSOME, determines the "sex" of the bacterium, host chromosome mobilization, transfer via conjugation (CONJUGATION, GENETIC) of genetic material, and the formation of SEX PILI.QuinolizinesPyrroles: Azoles of one NITROGEN and two double bonds that have aromatic chemical properties.Electrophoresis, Agar Gel: Electrophoresis in which agar or agarose gel is used as the diffusion medium.Macromolecular Substances: Compounds and molecular complexes that consist of very large numbers of atoms and are generally over 500 kDa in size. In biological systems macromolecular substances usually can be visualized using ELECTRON MICROSCOPY and are distinguished from ORGANELLES by the lack of a membrane structure.Glycosides: Any compound that contains a constituent sugar, in which the hydroxyl group attached to the first carbon is substituted by an alcoholic, phenolic, or other group. They are named specifically for the sugar contained, such as glucoside (glucose), pentoside (pentose), fructoside (fructose), etc. Upon hydrolysis, a sugar and nonsugar component (aglycone) are formed. (From Dorland, 28th ed; From Miall's Dictionary of Chemistry, 5th ed)Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Isopropyl Thiogalactoside: A non-metabolizable galactose analog that induces expression of the LAC OPERON.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.Peptides, Cyclic: Peptides whose amino and carboxy ends are linked together with a peptide bond forming a circular chain. Some of them are ANTI-INFECTIVE AGENTS. Some of them are biosynthesized non-ribosomally (PEPTIDE BIOSYNTHESIS, NON-RIBOSOMAL).Crystallography, X-Ray: The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Mycobacterium: A genus of gram-positive, aerobic bacteria. Most species are free-living in soil and water, but the major habitat for some is the diseased tissue of warm-blooded hosts.Gene Expression Regulation, Bacterial: Any of the processes by which cytoplasmic or intercellular factors influence the differential control of gene action in bacteria.Aza CompoundsKinetics: The rate dynamics in chemical or physical systems.Protein Subunits: Single chains of amino acids that are the units of multimeric PROTEINS. Multimeric proteins can be composed of identical or non-identical subunits. One or more monomeric subunits may compose a protomer which itself is a subunit structure of a larger assembly.Sequence Analysis, DNA: A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.Bacillus subtilis: A species of gram-positive bacteria that is a common soil and water saprophyte.Amino Acid Isomerases: Enzymes that catalyze either the racemization or epimerization of chiral centers within amino acids or derivatives. EC 5.1.1.Bacteriophage lambda: A temperate inducible phage and type species of the genus lambda-like viruses, in the family SIPHOVIRIDAE. Its natural host is E. coli K12. Its VIRION contains linear double-stranded DNA with single-stranded 12-base 5' sticky ends. The DNA circularizes on infection.Mycobacterium tuberculosis: A species of gram-positive, aerobic bacteria that produces TUBERCULOSIS in humans, other primates, CATTLE; DOGS; and some other animals which have contact with humans. Growth tends to be in serpentine, cordlike masses in which the bacilli show a parallel orientation.RNA, Bacterial: Ribonucleic acid in bacteria having regulatory and catalytic roles as well as involvement in protein synthesis.Heterocyclic Compounds: Ring compounds having atoms other than carbon in their nuclei. (Grant & Hackh's Chemical Dictionary, 5th ed)
"Glutamate Racemase is an Endogenous DNA Gyrase Inhibitor". Journal of Biological Chemistry. 277 (42): 39070-3. doi:10.1074/jbc. ... Racemization and DNA gyrase inhibition are two independent activities of the enzyme". Microbiology. 154 (9): 2796-803. doi: ... An inhibitor of porphobilinogen synthase with this mechanism of action has been documented. The morpheein model of allosteric ... Deprez, E.; Tauc, P.; Leh, H.; Mouscadet, J.-F.; Auclair, C.; Hawkins, M. E.; Brochon, J.-C. (2001). "DNA binding induces ...
The aminocoumarin antibiotics are known inhibitors of DNA gyrase. Antibiotics of the aminocoumarin family exert their ... Their affinity for gyrase is considerably higher than that of modern fluoroquinolones, which also target DNA gyrase but at the ... Aminocoumarin is a class of antibiotics that act by an inhibition of the DNA gyrase enzyme involved in the cell division in ... X-ray crystallography studies have confirmed binding at the ATP-binding site located on the gyrB subunit of DNA gyrase. ...
"New Antibacterial Agents Derived from the DNA Gyrase Inhibitor Cyclothialidine". Journal of Medicinal Chemistry. 47 (6): 1487- ... Hahn, edited by Fred E. (1983). Modes and Mechanisms of Microbial Growth Inhibitors. Berlin, Heidelberg: Springer Berlin ...
The antibiotic works by inhibiting the enzyme DNA gyrase. It also acts as a dopamine reuptake inhibitor and has stimulant ... "Behavioural and neurochemical evidence that the antimicrobial agent oxolinic acid is a dopamine uptake inhibitor". European ...
Castora, F. J.; Vissering, F. F.; Simpson, M. V. (September 1983). "The effect of bacterial DNA gyrase inhibitors on DNA ... Quinolones inhibit the bacterial DNA gyrase or the topoisomerase IV enzyme, thereby inhibiting DNA replication and ... Structure of bacterial DNA gyrase complexed with DNA and two ciprofloxacin molecules (green) ... Fourth-generation fluoroquinolones act at DNA gyrase and topoisomerase IV.[87] This dual action slows development of resistance ...
Castora, F. J.; Vissering, F. F.; Simpson, M. V. (September 1983). "The effect of bacterial DNA gyrase inhibitors on DNA ... Quinolones inhibit the bacterial DNA gyrase or the topoisomerase IV enzyme, thereby inhibiting DNA replication and ... It is believed eukaryotic cells do not contain DNA gyrase or topoisomerase IV. However, there is debate concerning whether the ... For many gram-negative bacteria, DNA gyrase is the target, whereas topoisomerase IV is the target for many gram-positive ...
However, in the MfpA protein a DNA gyrase inhibitor it has been suggested that the pentapeptide repeat structure mimics the ... June 2005). "A fluoroquinolone resistance protein from Mycobacterium tuberculosis that mimics DNA". Science. 308 (5727): 1480-3 ... structure of DNA. The repeats form a regular right handed four sided beta helix structure known as the Rfr-fold. The ...
Aminocoumarins are very potent inhibitors of bacterial DNA gyrase and work by targeting the GyrB subunit of the enzyme involved ... Maxwell A (1999). "DNA gyrase as a drug target". Biochem Soc Trans. 27 (2): 48-53. PMID 10093705. Lewis R. J.; Tsai F. T. F.; ... The potency of novobiocin is considerably higher than that of the fluoroquinolones that also target DNA gyrase, but at a ... X-ray crystallographic studies have found that the drug-receptor complex of Novobiocin and DNA Gyrase shows that ATP and ...
A comparison of active site binding of 4-quinolones and novel flavone gyrase inhibitors to DNA gyrase. Adv. Exp. Med. Biol. ... Formation of transient covalent protein and DNA adducts by quercetin in cells with and without oxidative enzyme activity. Chem ...
Posttranslational modifications in microcin B17 define an additional class of DNA gyrase inhibitor. Proc Natl Acad Sci U S A. ... Plasmid R6K DNA replication. II. Direct nucleotide sequence repeats are required for an active gamma-origin. J Mol Biol. 1982 ... His work defined an origin of DNA replication that led to the development of many suicide cloning vectors still in use today. ... Example publications Almirón M, Link AJ, Furlong D, Kolter R. A novel DNA-binding protein with regulatory and protective roles ...
... which causes DNA inter-strand crosslinks), norfloxacin, ofloxacin and nalidixic acid (inhibitors of DNA gyrase that cause ... a DNA damaging agent. In Helicobacter pylori, ciprofloxacin, which interacts with DNA gyrase and introduces double-strand ... They isolated DNA from a virulent strain of S. pneumoniae and using just this DNA were able to make a harmless strain virulent ... The DNA first binds to the surface of the competent cells on a DNA receptor, and passes through the cytoplasmic membrane via ...
Fisher, L. Mark; Pan, Xiao-Su (2008), "Methods to Assay Inhibitors of DNA Gyrase and Topoisomerase IV Activities", New ... a putative inhibitor of apoptosis, is a potent inhibitor of DNA topoisomerase II in vitro and in Chinese hamster fibrosarcoma ... These inhibitors are split into two main classes: topoisomerase poisons, which target the topoisomerase-DNA complex, and ... Use of topoisomerase inhibitors for antineoplastic treatments may lead to secondary neoplasms because of DNA damaging ...
Classic DNA inhibitors such as the quinolones act upon DNA gyrase as a topoisomerase inhibitor. Another group of DNA inhibitors ... RNA inhibitors such as rifampin, act upon DNA-dependent RNA polymerase. Antifolates act primarily as inhibitors of both RNA and ... There are two major classes: DNA inhibitors and RNA inhibitors. The antifungal flucytosine acts in a similar manner. ... DNA, and are often grouped with nucleic acid inhibitors in textbooks. However, they also act indirectly as protein synthesis ...
It functions by inhibiting DNA gyrase, a type II topoisomerase, and topoisomerase IV, which is an enzyme necessary to separate ... There are a number of the endogenous compounds that have been reported to be affected by ofloxacin as inhibitors, alteraters ... Drlica K, Zhao X (1 September 1997). "DNA gyrase, topoisomerase IV, and the 4-quinolones". Microbiol Mol Biol Rev. 61 (3): 377- ... It works by interfering with the bacterium's DNA. Ofloxacin was patented in 1980 and approved for medical use in 1985. It is on ...
MurI also acts as a gyrase inhibitor, preventing gyrase from binding to DNA. The two processes have been shown two be unrelated ... MurI reduces the activity of DNA gyrase by preventing gyrase from binding to DNA. When gyrase binds to DNA, the enzyme ... DNA gyrase was incubated with the MurI enzyme and then added to a sample of DNA; the results of this experiment showed ... The gyrase inhibition occurs in both supercoiling and relaxing activities of the DNA gyrase, and the study concluded that the ...
Kampranis SC, Bates AD, Maxwell A (July 1999). "A model for the mechanism of strand passage by DNA gyrase". Proc. Natl. Acad. ... Direct inhibitors of ATP binding or allosteric inhibitors of either ATP binding or ATPase activity can block Hsp90 function. ... The drug was originally thought to function as a kinase inhibitor but was subsequently shown to be an Hsp90 inhibitor where it ... Gyrase, Hsp90, Histidine Kinase, MutL) superfamily. A common binding pocket for ATP and the inhibitor geldanamycin is situated ...
"Interactions of CcdB with DNA gyrase. Inactivation of Gyra, poisoning of the gyrase-DNA complex, and the antidote action of ... one a potent inhibitor of cell proliferation (toxin) and the other its specific antidote (antitoxin). These systems ... In absence of the antitoxin, the CcdB poison traps DNA-gyrase cleavable complexes, inducing breaks into DNA and cell death. ... The target of CcdB is the GyrA subunit of DNA gyrase, an essential type II topoisomerase in Escherichia coli. ...
... or DNA gyrase (the target in Gram-negative bacteria), preventing the bacteria from unwinding their DNA and undergoing either ... studied the use of quinoline derivatives as HIV-1 integrase inhibitors.[8] Conrad, M.; Limpach, L. synthesen von ... "Synthesis and Biological Activities of Quinoline Derivatives as HIV-1 Integrase Inhibitors" (pdf). Chem. Res. Chinese ... DNA replication or transcription. The majority of drugs in clinical use are actually quinoline derivatives that belong to the ...
... inhibitors of DNA gyrase that cause double-strand breaks), bicyclomycin (causes double-strand breaks) and hydroxyurea (causes ... In order for a bacterium to bind, take up, and recombine exogenous DNA into its chromosome, it must enter a special ... In-depth comparative genome analysis using DNA arrays to study the gene content of 180 Legionella strains revealed high genome ... Only six of these molecules, all DNA damaging agents, caused strong induction of competence. These were mitomycin C (which ...
... in 1981 from Department of Microbiology and Cell Biology at IISc and the work on mycobacteriophage I3 and role of DNA gyrase in ... new inhibitors for the generation of lead molecules as a step for novel therapeutics against tuberculosis. These have been ... in 1981 from Department of Microbiology and Cell Biology at IISc and the work on mycobacteriophage I3 and role of DNA gyrase in ... His interaction with industry includes - development of commercial biotech products such as restriction enzymes and other DNA ...
ParD forms a dimer and also regulates its own promoter (parDE). As with CcdB the toxin target is DNA gyrase. Induction of ParE ... one a potent inhibitor of cell proliferation (toxin) and the other its specific antidote (antitoxin). These systems ... ParD is a plasmid anti-toxin that forms a ribbon-helix-helix DNA binding structure. It stabilises plasmids by inhibiting ParE ... ParD of plasmid RK2 consists of two structurally distinct moieties and belongs to the ribbon-helix-helix family of DNA-binding ...
It functions by inhibiting DNA gyrase, and a type II topoisomerase, topoisomerase IV,[68][69] necessary to separate bacterial ... Ciprofloxacin is a potent inhibitor of CYP1A2, CYP2D6, and CYP3A4.[67]. Mechanism of action[edit]. Ciprofloxacin is a broad- ... "DNA gyrase, topoisomerase IV, and the 4-quinolones". Microbiology and Molecular Biology Reviews. 61 (3): 377-92. PMC 232616 . ... Ciprofloxacin is weakly bound to serum proteins (20-40%), but is an inhibitor of the drug-metabolizing enzyme cytochrome P450 ...
The single-strand viral DNA ends are ligated by host DNA ligase. Host DNA gyrase puts negative supercoils in the circular ... cIII appears to stabilize cII, both directly and by acting as a competitive inhibitor to the relevant proteases. This means ... The original B-O-B' sequence is changed by the integration to B-O-P'-phage DNA-P-O-B'. The phage DNA is now part of the host's ... The 48 kb DNA fragment of lambda phage is not essential for productive infection and can be replaced by foreign DNA. Lambda ...
DNA gyrase B and HSP90. This domain is found in several ATP-binding proteins for example: histidine kinase, DNA gyrase B, ... "Structure-activity relationships in purine-based inhibitor binding to HSP90 isoforms". Chem. Biol. 11 (6): 775-85. doi:10.1016/ ... a Single Residue Dictates Differences in Novobiocin Potency against Topoisomerase IV and DNA Gyrase". Antimicrob. Agents ... The GHKL domain (Gyrase, Hsp90, Histidine Kinase, MutL) is an evolutionary conserved protein domain. This family represents the ...
... the older gyrase-inhibitors such as cinoxacin are no longer indicated... Cinoxacin is one of the original quinolone drugs, ... "DNA gyrase, topoisomerase IV, and the 4-quinolones". Microbiol Mol Biol Rev. 61 (3): 377-92. PMC 232616 . PMID 9293187. A ... Cinoxacin mode of action involves the inhibiting of DNA gyrase, a type II topoisomerase, and topoisomerase iv, which is an ... enzyme necessary to separate replicated DNA, thereby inhibiting cell division. Within the most recent package insert (circa ...
Quinolones inhibit the bacterial DNA gyrase or the topoisomerase IV enzyme, thereby inhibiting DNA replication and ... Antibacterials: nucleic acid inhibitors (J01E, J01M). Antifolates. (inhibits. purine metabolism,. thereby inhibiting. DNA and ... For many gram-negative bacteria DNA gyrase is the target, whereas topoisomerase IV is the target for many gram-positive ...
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 ... Can also protect cells against alkylating agents that act independently of DNA gyrase, suggesting a more general role in ... against toxins that target DNA gyrase, by inhibiting activity of these toxins and reducing the formation of lethal double- ... "Characterization of the interaction between DNA gyrase inhibitor and DNA gyrase of Escherichia coli.". Nakanishi A., Imajoh- ...
Inhibition of DNA gyrase blocks relaxation of supercoiled DNA, relaxation being a requirement for transcription and replication ... Bacterial DNA gyrase (topoisomerase II) and topoisomerase IV are required for DNA synthesis. ... Fluoroquinones represent an important class of antimicrobial which work through inhibition of DNA gyrase. ... Inhibition of topoisomerase IV is thought to interfere with sepation of replicated chromosomal DNA ...
Pyrrolopyrimidine inhibitors of dna gyrase b and topoisomerase iv, part i: structure guided discovery and optimization of dual ... Pyrrolopyrimidine inhibitors of dna gyrase b and topoisomerase iv, part i: structure guided discovery and optimization of dual ... Pyrrolopyrimidine inhibitors of DNA gyrase B (GyrB) and topoisomerase IV (ParE). Part I: Structure guided discovery and ... The bacterial topoisomerases DNA gyrase (GyrB) and topoisomerase IV (ParE) are essential enzymes that control the topological ...
Pyrrolopyrimidine inhibitors of DNA gyrase B (GyrB) and topoisomerase IV (ParE). Part I: Structure guided discovery and ... Pyrrolopyrimidine inhibitors of DNA gyrase B and topoisomerase IV, part I: structure guided discovery and optimization of dual ...
Design, synthesis and antibacterial properties of pyrimido[4,5-b]indol-8-amine inhibitors of DNA gyrase ... indol-8-amine inhibitors of DNA gyrase. Bioorganic and Medicinal Chemistry Letters, 28 (17). pp. 2998-3003. ISSN 0960-894X ... ESKAPE pathogens, anti-infectives, topoisomerases, DNA gyrase, pyrimido[45-b]indol-8-amine, Chemistry, Chemistry(all). ... indol-8-amine inhibitors of bacterial type II topoisomerases. Compounds from the series were highly potent against gram- ...
... Karkare, Shantanu; Chung, Terence ... The naphthoquinone diospyrin is an inhibitor of DNA gyrase with a novel mechanism of action. Login ... The DNA topoisomerases are excellent targets for chemotherapy, and DNA gyrase in particular is a well-validated target for ... We have found that these compounds are inhibitors of the supercoiling reaction catalyzed by M. tuberculosis gyrase and other ...
Ciprofloxacin Control Poison Inhibitor of DNA Gyrase and Topo IV Available from TopoGEN ... A control poison/inhibitor of DNA Gyrase and Topo IV. This is also included in the Topo IV/Gyrase Drug Screening Kits. ... This short video describes our new Cell Based Screening Systems for DNA Repair. Mouse and human cell line kits are available, ... This short video describes our new Cell Based Screening Systems for DNA Repair. Mouse and human cell line kits are available, ...
Marbofloxacin is a bacterial DNA gyrase inhibitor. It suppresses growth of Staphylococus, Escherichia, Actinobacillus, ... Description: Marbofloxacin is a bacterial DNA gyrase inhibitor. It suppresses growth of Staphylococus, Escherichia, ... Leading supplier of anticancer chemical reagents and kinase inhibitors Tel: +1-919-636-5577 Fax: +1-919-980-4831 Email: [email protected] ...
The role of DNA gyrase -a type II topoisomerase- had been speculated about for a long time before the discovery of the enzyme. ... Cell Free Extract Nalidixic Acid Oxolinic Acid Solid Phase Radioimmunoassay Gyrase Inhibitor These keywords were added by ... Orr E., Lother H., Lurz R., Wahle E. (1984) Escherichia coli DNA Gyrase. In: Proteins Involved in DNA Replication. Advances in ... all dependent on the DNA template. DNA gyrase has now become a most promiscuous protein, participating in different molecular ...
DNA gyrase inhibitor. Shigella boydii serotype 18 (strain CDC 3083-94 / BS512) ... DNA gyrase inhibitor UniProtKBInterProInteractive Modelling. 157 aa; Sequence (Fasta) 27 identical sequences 27 identical ... Crystal Structure of the Escherichia coli SbmC protein (AKA Gyrase Inhibitory Protein GyrI, AKA Yee…. monomer 1jyh. 1-155. ...
... to antibiotic discovery include small-molecule screens for growth inhibition in target pathogens and screens for inhibitors of ... Second, we have identified a DNA gyrase inhibitor. This molecule, EN-7, is active against pathogenic species that are resistant ... Discovery of a Novel DNA Gyrase-Targeting Antibiotic through the Chemical Perturbation of Streptomyces venezuelae Sporulation. ... Discovery of a Novel DNA Gyrase-Targeting Antibiotic through the Chemical Perturbation of Streptomyces venezuelae Sporulation. ...
... August 31, 2020 ... Home » Efficacy and mechanism of action of novel DNA gyrase inhibitors against mycobacteria ... Discovery of novel HIF-PHD2 inhibitors for the treatment of anemia BG-P-TAT, novel dual targeting agent with promising efficacy ...
Ofloxacin is a DNA gyrase inhibitor. DNA gyrase is an essential bacterial enzyme that maintains the superhelical structure of ... DNA gyrase is required for DNA replication and transcription, DNA repair, recombination, and transposition; bactericidal ...
Ethyl Urea Inhibitors of the Bacterial Type II Topoisomerases DNA Gyrase (GyrB) and Topoisomerase IV (ParE). Stephen P. East, ... The Rational Design of Triple Reuptake Inhibitors for the Treatment of Depression. Robert J. Weikert ... Targeting Protein-Protein Interactions: Dual Inhibitors of Bcl-2 and Bcl-xL. Michael D. Wendt ... Comprehensive track record of research, publications and presentations in the areas of enzyme inhibitors, prostaglandins, ...
What are the two enzymes that are inhibited by DNA synthesis inhibitors? ... What are the 5 classes of antibiotics that fall under the protein synthesis inhibitors class? ...
dna gyrase inhibitor 25 quinolone coverage good gram-. cipro pseudomonas. moxi anaerobes. levo best gram+ ...
"Glutamate Racemase is an Endogenous DNA Gyrase Inhibitor". Journal of Biological Chemistry. 277 (42): 39070-3. doi:10.1074/jbc. ... Racemization and DNA gyrase inhibition are two independent activities of the enzyme". Microbiology. 154 (9): 2796-803. doi: ... An inhibitor of porphobilinogen synthase with this mechanism of action has been documented. The morpheein model of allosteric ... Deprez, E.; Tauc, P.; Leh, H.; Mouscadet, J.-F.; Auclair, C.; Hawkins, M. E.; Brochon, J.-C. (2001). "DNA binding induces ...
Maxwell A (1993) The interaction between coumarin drugs and DNA gyrase. Mol Microbiol 9(4):681-686. https://doi.org/10.1111/j. ... Inhibition of archaeal growth and DNA topoisomerase VI activities by the Hsp90 inhibitor radicicol. Nucleic Acids Res 33(7): ... Shi J, Van de Water R, Hong K et al (2012) EC144 is a potent inhibitor of the heat shock protein 90. J Med Chem 55:7786-7795 ... Matts RL, Dixit A, Peterson LB et al (2011b) Elucidation of the Hsp90 C-terminal inhibitor binding site. ACS Chem Biol 6:800- ...
The aminocoumarin antibiotics are known inhibitors of DNA gyrase. Antibiotics of the aminocoumarin family exert their ... Their affinity for gyrase is considerably higher than that of modern fluoroquinolones, which also target DNA gyrase but at the ... Aminocoumarin is a class of antibiotics that act by an inhibition of the DNA gyrase enzyme involved in the cell division in ... X-ray crystallography studies have confirmed binding at the ATP-binding site located on the gyrB subunit of DNA gyrase. ...
1 Dougherty, T.J., & Saukkonenn, J.J. Membrane permeability changes associated with DNA gyrase inhibitors in Escherichia coli. ... Microbiology: Quinolone carboxylic acid derivatives are classified as DNA gyrase inhibitors. The mechanism of action of these ... The site of action is bacterial gyrase, a synthesis promoting enzyme. The effect on Escherichia coli is the inhibition of DNA ... synthesis through prevention of DNA supercoiling. Among other things, such compounds lead to the cessation of cell respiration ...
Topoisomerase IV and DNA gyrase inhibitor. Reversibly inhibits DNA synthesis. Inhibits PANX1 (IC50 = 4 μM). Shows antibiotic ... Activity of the new fluoroquinolone trovafloxacin (CP-99,219) against DNA gyrase and topoisomerase IV mutants of Streptococcus ... Agonists, activators, antagonists and inhibitors. Cell lines and Lysates. Multiplex Assays. By research area. Cancer. ...
Interaction Between the DNA-Gyrase Inhibitor Coumermycin and the Membrane of Human Neutrophils ... Effect of Beta-Lactam Antibiotics on Eukaryotic DNA Replication: Possible Impact on the Host-Parasite Relationship ...
C. DNA gyrase / RNA polymerase (Nucleic Acid Synthesis) INHIBITOR 1) Quinolones. Fluoroquinolones. Essential structure of all ... Synthetic fluorinated analogs of nalidixic acid Inhibit bacterial DNA synthesis Inhibit DNA gyrase & topoisomerase Examples ... Resistance develops due to the ability of DNA:To undergo spontaneous mutation To move from one organism to another (DNA/gene ... 3. Beta-lactamase inhibitors. 1) Clavulanic acid 2) Sulbactam. Cell wall inhibitors. 1. -lactam antibiotics. Penicillins ...
The CcdB and ParE toxins are DNA gyrase inhibitors; the RelE, Doc, and HigB toxins directly or indirectly cleave ribosome- ... Genomic DNA and cDNA were used as the templates in traditional PCRs utilizing Taq DNA polymerase (Invitrogen) and gene ( ... A single strand of pentaprobe DNA was amplified by asymmetric PCR from the template pentaprobe PCR product using the Pfx DNA ... The resulting plasmid was sequence verified and used as a DNA template in subsequent PCRs. The Pfx DNA polymerase system ( ...
DNA gyrase inhibitor (yacG), encoding an inhibitor of GyrB, maps close to the center. Chromosomal partition genes C and E (parC ... a component of DNA gyrase responsible for increasing negative superhelicity, maps close to OriC, whereas the gyrase inhibitor ... Similarly, gyrB (but not gyrA), encoding subunit B of DNA gyrase, is located in close proximity to OriC. Gyrase increases ... 3 A and E), implicated in evolutionary modulation of DNA superhelicity (25). We infer that the gradient of gyrase binding sites ...
  • While the number of Hsp90 inhibitors described in the literature has dramatically increased since the first such small molecule was described in 1994, it has become increasingly apparent that not all of these agents have been sufficiently validated for specificity, mechanism of action, and lack of off-target effects. (springer.com)
  • Given the less than expected activity of Hsp90 inhibitors in cancer-related human clinical trials, a re-evaluation of potentially confounding off-target effects, as well as confidence in target specificity and mechanism of action, is warranted. (springer.com)
  • An inhibitor of porphobilinogen synthase with this mechanism of action has been documented. (wikipedia.org)
  • The high degree of conservation in the ATP-binding pockets of these enzymes make them appealing targets for broad-spectrum inhibitor development. (rcsb.org)
  • Grepafloxacin exerts its antibacterial activity by inhibiting bacterial topoisomerase II (DNA gyrase) and topoisomerase IV, essential enzymes for duplication, transcription, and repair of bacterial DNA. (drugbank.ca)
  • Similar selections with PALA, N -(phosphonacetyl)- l -aspartate, and methotrexate led to amplification of specific genes encoding enzymes targeted by the inhibitors in mammalian cells ( 34 , 41 ). (asm.org)
  • DNA topoisomerase I and II (Topo I and Topo II) are nuclear enzymes that regulate the topological structure of DNA in eukaryotic cells by transiently breaking and rejoining DNA strands. (scbt.com)
  • Large scale production of these enzymes using recombinant DNA technology in our academic laboratory is utilised to avoid dependence on expensive commercially available enzymes. (ejbiotechnology.info)
  • For example, enzymes that cleave only one strand of DNA are defined as type I with a further classification of type I-A subtypes for proteins linked to a 5'-phosphate and type I-B subtypes for proteins attached to a 3'-phosphate during the relaxation of the cleavable DNA. (ejbiotechnology.info)
  • All inhibitors of early cell wall synthesis caused reduction of methicillin resistance and change from the homogeneous to the heterogeneous methicillin-resistant phenotype. (nih.gov)
  • Whole-cell assays were implemented to search for efflux pump inhibitors (EPIs) of the three multidrug resistance efflux pumps (MexAB-OprM, MexCD-OprJ, MexEF-OprN) that contribute to fluoroquinolone resistance in clinical isolates of Pseudomonas aeruginosa . (asm.org)
  • We show that the highly conserved spatial ordering of relevant genes along the chromosomal replichores largely corresponds both to their temporal expression patterns during growth and to an inferred gradient of DNA superhelical density from the origin to the terminus. (pnas.org)
  • Genes implicated in similar functions are related mainly in trans across the chromosomal replichores, whereas DNA-binding transcriptional regulators interact predominantly with targets in cis along the replichores. (pnas.org)
  • Second bar ) Selected genes involved in control of DNA topology. (pnas.org)
  • Chromosomal partition genes C and E ( parC and parE ) encode the subunits of topoisomerase IV, responsible for decatenation of newly replicated DNA in the terminal region ( 64 ) and relaxation of negative supercoils ( 65 ). (pnas.org)
  • Targets of inhibitor action were verified by using these methods ( 31 ), while the ability to define both target-specifying and unexpected resistance genes was uncovered ( 17 ). (asm.org)
  • The sequencing of insert-vector junctions defines genes that confer inhibitor resistance when present in high copy. (asm.org)
  • DNA in intracellular Salmonella enterica serovar Typhimurium relaxes during growth in the acidified (pH 4-5) macrophage vacuole and DNA relaxation correlates with the upregulation of Salmonella genes involved in adaptation to the macrophage environment. (jic.ac.uk)
  • As reviewed by Roth [ 7 ], the mechanisms include: occult growth of a sub-population aided by the residual activity of the defective gene product and amplification of the gene by homologous recombination, both of which increase the number of mutational targets, and stress-related amplification, and possibly induction of dinB , which encodes an error-prone DNA polymerase that may produce mutations during gene amplification. (prolekare.cz)
  • These newer drugs, highlighted by norfloxacin, ciprofloxacin, and ofloxacin, displayed considerably improved activity against gyrase, greater penetration into Gram-positive organisms, and enhanced pharmacokinetics and pharmacodynamics [ 5 ]. (hindawi.com)
  • Hybridization of these historical compounds with the quinazolinediones, a known series of topoisomerase inhibitors, led us to a novel series of tricyclic IPYs that demonstrated potential for broad spectrum activity, in vivo efficacy and a good developability profile although later profiling revealed a genotoxicity risk. (bioportfolio.com)
  • An EC 3.6.4.10 (non-chaperonin molecular chaperone ATPase) inhibitor that blocks the action of heat shock protein 90. (ebi.ac.uk)