• DNA gyrase, or simply gyrase, is an enzyme within the class of topoisomerase and is a subclass of Type II topoisomerases that reduces topological strain in an ATP dependent manner while double-stranded DNA is being unwound by elongating RNA-polymerase or by helicase in front of the progressing replication fork. (wikipedia.org)
  • The ability of gyrase (and topoisomerase IV) to relax positive supercoils allows superhelical tension ahead of the polymerase to be released so that replication can continue. (wikipedia.org)
  • Inhibits topoisomerase II (DNA gyrase) and IV enzymes. (medscape.com)
  • Topoisomerase IV plays a key role in chromosomal DNA portioning during bacterial cell division. (medscape.com)
  • Then, using the energy from a second ATP, Type II topoisomerase reseals the broken ends of the DNA strands and finally detaches from the DNA- leaving behind an untangled DNA helix. (jove.com)
  • With the exception of reverse gyrase, this unique type IA topoisomerase does require ATP and generates positive DNA supercoils rather than unwinding them. (jove.com)
  • Selected flavonoids were tested for their ability to inhibit the catalytic activity of DNA topoisomerase (topo) I and II. (ucy.ac.cy)
  • Further analysis found protein-linked double-stranded DNA breaks in the mtDNA from ciprofloxacin-treated cells, suggesting that ciprofloxacin was targeting topoisomerase II activity in the mitochondria. (hormonesmatter.com)
  • These are the enzymes topoisomerase II (gyrase) and topoisomerase IV. (healthandmedicineinfo.com)
  • After this process, the DNA strand twists again, which requires the two enzymes topoisomerase II and IV. (healthandmedicineinfo.com)
  • It displayed potent inhibitory effects on topoisomerases II (DNA gyrase and topoisomerase IV) as potential molecular targets, with IC50 values of 6.754 and 1.913 µg/mL, respectively, in contrast to Cpx, which had IC50 values of 2.125 and 0.821 µg/mL, respectively. (bvsalud.org)
  • Herein, we report a sub-series of tricyclic NBTIs bearing an amide linkage that displays promising antibacterial activity, potent dual-target inhibition of DNA gyrase and topoisomerase IV (TopoIV), as well as improved cardiovascular safety and metabolic profiles. (bvsalud.org)
  • Unexpectedly, amides 1a and 1b targeted human topoisomerase IIα (TOP2α) causing both single- and double-strand breaks in pBR322 DNA, and induced DNA strand breaks in intact human leukemia K562 cells. (bvsalud.org)
  • The intention behind the preparation of the complex was to increase cellular uptake, compare its binding with DNA against that of quinalizarin, modulation of semiquinone formation, realization of human DNA topoisomerase I & human DNA topoisomerase II inhibition and observation of anticancer activity. (bvsalud.org)
  • Inhibition of human DNA topoisomerase makes up this envisaged compromise in free radical activity since the complex shows remarkable ability to disrupt activities of human DNA topoisomerase I and II. (bvsalud.org)
  • eukaryotic topoisomerase I and topoisomerase V). These enzymes are primarily responsible for relaxing positively and/or negatively supercoiled DNA, except for reverse gyrase, which can introduce positive supercoils into DNA. (embl.de)
  • This entry represents the C-terminal region of DNA topoisomerase I enzymes from eukaryotes (type IB enzymes). (embl.de)
  • The crystal structures of human topoisomerase I comprising the core and carboxyl-terminal domains in covalent and noncovalent complexes with 22-base pair DNA duplexes reveal an enzyme that 'clamps' around essentially B-form DNA. (embl.de)
  • We also offer a complete line of DNA substrates and DNA cleavage targets , topoisomerase inhibitors , topoisomerase antibodies , and kit replenishment reagents . (e-biochem.com)
  • Our cell based (in vivo) screens for detecting topoisomerase I and II poisons in the context of the cancer cell represents the new gold standard for identification of novel anti cancer agents. (e-biochem.com)
  • The bactericidal action of lomefloxacin results from interference with the activity of the bacterial enzymes DNA gyrase and topoisomerase IV, which are needed for the transcription and replication of bacterial DNA. (buyotcantibiotics.com)
  • Fluoroquinolones are topoisomerase interrupters, meaning a role in the host defense against infection, as TLR2 action of ciprofloxacin results from Newman parental Ampicillin discount displayed enhanced II (DNA gyrase) and topoisomerase increased weight loss, mortality and bacterial burden in kidneys compared to the wild The importance recombination. (uokraskom.com)
  • Levofla kills bacteria by turning two bacterial enzymes, topoisomerase IV and DNA gyrase, into harmful enzymes that impair DNA synthesis and repair, as well as other DNA activities, thereby killing the bacterium. (healthsoothe.com)
  • Irinotecan causes cell toxicity by stabilizing a ternary complex between the nuclear enzyme topoisomerase I (topo I) and double-stranded DNA, leading to single and double strand breaks. (topogen.com)
  • however, cleavages are strongly influenced by the amount of topoisomerase in the reaction as well as the type of assay being employed (SDSK+ vs. Radioactive End Labeled DNA vs. testing for plasmid cleavages). (topogen.com)
  • Lomefloxacin hydrochloride inhibits DNA gyrase, a type II topoisomerase involved in the induction or relaxation of supercoiling during DNA replication. (medindex.am)
  • It is the only known enzyme to actively contribute negative supercoiling to DNA, while it also is capable of relaxing positive supercoils. (wikipedia.org)
  • The helical nature of the DNA causes positive supercoils to accumulate ahead of a translocating enzyme, in the case of DNA replication, a DNA polymerase. (wikipedia.org)
  • DNA gyrase is a tetrameric enzyme that consists of 2 GyrA ("A") and 2 GyrB ("B") subunits. (wikipedia.org)
  • On a next step the enzyme cleaves a G-segment of DNA (G- from gate) making a double-strand break. (wikipedia.org)
  • DNA-gyrase ligates the break in a G-segment back and T-segment finally leaves the enzyme complex. (wikipedia.org)
  • The gyrase motif reflects wrapping of DNA around the enzyme complex and DNA flexibility. (wikipedia.org)
  • The unbroken DNA strand is then passed through the gap in the broken strand into the upper cavity of the enzyme. (jove.com)
  • Finally, the enzyme ligates the broken ends of the DNA strands back together and produces a locally relaxed DNA molecule. (jove.com)
  • The enzyme creates a double strand break in one loop of the DNA double helix before helping the unbroken loop to pass through this break via an ATP-dependent reaction. (jove.com)
  • The enzyme rotates the cut single-strand around the opposite strand, untwisting the DNA in the process. (jove.com)
  • This enzyme binds to DNA and, through a series of elegant movements, twists it up in a process known as supercoiling, vital for cells to function properly. (growkudos.com)
  • Docking studies further supported these findings, showing that Cpx-Drv exhibited stronger binding interactions with the gyrase enzyme (PDB ID: 2XCT) compared to the parent Cpx, with binding affinities of -10.3349 and -7.7506 kcal/mole, respectively. (bvsalud.org)
  • The core domain and the first eight residues of the carboxyl-terminal domain of the enzyme, including the active-site nucleophile tyrosine-723, share significant structural similarity with the bacteriophage family of DNA integrases. (embl.de)
  • To make an enzyme that it needs, the chemical mechanisms inside an E. coli cell make a copy of a gene from the DNA strand and use this template to form the enzyme. (howstuffworks.com)
  • A section of the DNA strand, called a gene , tells the cell how to manufacture one enzyme. (howstuffworks.com)
  • The process of manufacturing an enzyme from a gene on the DNA strand is amazing -- see How Cells Work for details. (howstuffworks.com)
  • Streptomycin, for example, is an antibiotic that can gum up the ribosome in a bacterium but leaves human ribosomes unharmed (a ribosome is a large enzyme that helps to turn DNA information into new enzymes). (howstuffworks.com)
  • Segments of DNA to be used in protein production must be uncoiled by an enzyme called DNA gyrase. (vin.com)
  • The ability of gyrase to relax positive supercoils comes into play during DNA replication and prokaryotic transcription. (wikipedia.org)
  • DNA gyrase is essential in bacterial DNA replication, transcription, and repair. (medscape.com)
  • The unwinding of the DNA double helix during replication results in overwinding in regions ahead of the replication fork. (jove.com)
  • Topoisomerases are enzymes that relax overwound DNA molecules during various cell processes, including DNA replication and transcription. (jove.com)
  • This inhibition leads to a decrease in DNA synthesis during bacterial replication, resulting in cell growth inhibition and eventually cell lysis. (medindex.am)
  • This process occurs in bacteria, whose single circular DNA is cut by DNA gyrase and the two ends are then twisted around each other to form supercoils. (wikipedia.org)
  • Antibiotics are used to select all types of plasmidic vectors in bacteria which is a significant concern in industrial cultures producing recombinant proteins or DNA. (igem.org)
  • If a plasmid carrying the ccd module is lost at cell division, the plasmid-free bacteria contain poison and antidote proteins in their cytoplasm. (igem.org)
  • We have hope that the unusual nature of the interaction between albicidin and gyrase will allow us and others to use it as a base to develop antibiotics that can overcome the threat of antibiotic resistant bacteria" commented Elizabeth Michalczyk, a PhD student in the Heddle lab and one of the lead authors of the work. (growkudos.com)
  • The DNA of the bacteria is a molecule in the form of a rope ladder. (healthandmedicineinfo.com)
  • The antibiotic is also suitable for inflammation of the soft tissues, skin infections, bone inflammation, infections in the pelvic and abdominal cavity, diarrhea caused by bacteria and blood poisoning (sepsis). (healthandmedicineinfo.com)
  • Its main function is to inhibit the deoxyribonucleic acid (DNA) gyrase of bacteria, so that the synthesis of deoxyribonucleic acid (DNA) protein is disturbed, so that the cells can no longer divide, thereby playing a sterilizing role. (ballyabio.com)
  • With its DNA now useless, the bacteria cannot make protein and dies. (vin.com)
  • A plasmid is an extra-chromosomal, self-replicative DNA molecule that naturally occurs in bacteria while transposon is a DNA sequence that moves around different positions within a genome. (pediaa.com)
  • Plasmids are double-stranded, circular DNA molecules, occurring in the cytoplasm of the bacteria, archaea , yeast , and protozoans . (pediaa.com)
  • The CcdB protein (poison) is cytotoxic and poisons DNA-gyrase complexes. (igem.org)
  • ccdB codes for the toxic protein (CcdB) that acts as a DNA gyrase poison, locking up DNA gyrase with broken double stranded DNA and ultimately causing cell death. (addgene.org)
  • One such strain is DB3.1 , which contains a mutant version of DNA gyrase (gyrA462) that is resistant to the toxic effects of CcdB. (addgene.org)
  • The ccd B gene is incorporated into the cloning site of Zero Background vectors.The CcdB protein poisons bacterial gyrase, causing degradation of the hose chromosome and cell death. (thermofisher.com)
  • A single molecule study has characterized gyrase activity as a function of DNA tension (applied force) and ATP, and proposed a mechanochemical model. (wikipedia.org)
  • It creates a single-strand breakthrough which the opposite strand can pass, resulting in a locally untangled DNA molecule. (jove.com)
  • For example, one of the 1,000 enzymes in an E. coli's DNA might know how to break a maltose molecule (a simple sugar) into its two glucose molecules. (howstuffworks.com)
  • Type I topoisomerases are ATP-independent and act by cutting a bond between nucleotides on a single strand of double stranded DNA. (jove.com)
  • The product of the ccdA gene (antidote) antagonizes this toxic activity by forming a poison-antidote protein complex. (igem.org)
  • And that "increases in ROS led to DNA, protein, and lipid damage in vitro. (hormonesmatter.com)
  • Blower, T. R. , Williamson, B. H. , Kerns, R. J. , and Berger, J. M. (2016) Crystal structure and stability of gyrase-fluoroquinolone cleaved complexes from Mycobacterium tuberculosis . (cornell.edu)
  • Gyrase has a pronounced specificity to DNA substrates. (wikipedia.org)
  • Many proteins have been identified as substrates for the kinase activity of DNA-PK. (dnapk-signaling.com)
  • DNA overwinding in a clockwise direction results in positively supercoiled DNA, whereas underwinding in a counterclockwise direction produces negatively supercoiled DNA. (jove.com)
  • Type IB forms a covalent bond with the 3' end of the broken DNA strand and can relax both positively and negatively supercoiled DNA. (jove.com)
  • Since the antidote is unstable and degraded by a host protease, the poison will be free and able to poison DNA-gyrase complexes. (igem.org)
  • Recently, high throughput mapping of DNA gyrase sites in the Escherichia coli genome using Topo-Seq approach revealed a long (≈130 bp) and degenerate binding motif that can explain the existence of SGSs. (wikipedia.org)
  • Unlike Topo IA enzymes, Topo IB enzymes do not require a single-stranded region of DNA or metal ions for their function. (embl.de)
  • We also provide custom compound screening services for topo poisons. (e-biochem.com)
  • The unique ability of gyrase to introduce negative supercoils into DNA at the expense of ATP hydrolysis is what allows bacterial DNA to have free negative supercoils. (wikipedia.org)
  • Structurally the complex is formed by 3 pairs of "gates", sequential opening and closing of which results into the direct transfer of DNA segment and introduction of 2 negative supercoils. (wikipedia.org)
  • As the result of a catalytic cycle two ATP molecules are hydrolyzed and two negative supercoils are introduced into the DNA template. (wikipedia.org)
  • Type IA forms a covalent bond with 5' end of the cleaved DNA strand and removes negative supercoils. (jove.com)
  • According to the catalytic cycle proposed, binding of 2 ATP molecules causes dimerization of ATPase domains of GyrB subunits and capturing of a T-segment of DNA (T- from transferring) in a cavity between GyrB subunits. (wikipedia.org)
  • The number of superhelical turns introduced into an initially relaxed circular DNA has been calculated to be approximately equal to the number of ATP molecules hydrolyzed by gyrase. (wikipedia.org)
  • Therefore, it can be suggested that two ATP molecules are hydrolyzed per cycle of reaction by gyrase, leading to the introduction of a linking difference of -2. (wikipedia.org)
  • Gyrase is present in prokaryotes and some eukaryotes, but the enzymes are not entirely similar in structure or sequence, and have different affinities for different molecules. (wikipedia.org)
  • You can think of the bacterium as a cell wall (think of the cell wall as a tiny plastic bag) filled with various proteins, enzymes and other molecules, plus a long strand of DNA , all floating in water . (howstuffworks.com)
  • Any cell has enzymes that help it digest food, add to the cell wall, duplicate DNA strands, produce energy molecules, and so on. (howstuffworks.com)
  • Gyrase is also found in eukaryotic plastids: it has been found in the apicoplast of the malarial parasite Plasmodium falciparum and in chloroplasts of several plants. (wikipedia.org)
  • The two regions correspond to DNA binding by C-terminal domains of GyrA subunits and resemble eukaryotic nucleosome binding motif. (wikipedia.org)
  • The company also provides assay kits for assaying both prokaryotic and eukaryotic topoisomerases (type I, II, IV, gyrase), both in vitro and in vivo. (e-biochem.com)
  • In vitro studies in drug-treated mammalian cells found that nalidixic acid and ciprofloxacin cause a loss of motichondrial DNA (mtDNA), resulting in a decrease of mitochondrial respiration and an arrest in cell growth. (hormonesmatter.com)
  • It turns out that mammalian DNA gyrase is of a completely different shape and remains untouched. (vin.com)
  • The mammalian genome comprises nuclear DNA (nDNA) derived from both parents and mitochondrial DNA (mtDNA) that is maternally inherited and encodes essential proteins required for oxidative phosphorylation. (regenerativemedicine.net)
  • Normally, gyrase quickly joints the two pieces of DNA back together again, but albicidin prevents this joining from occurring. (growkudos.com)
  • Despite its known antibiotic potential and low toxicity in pre-clinical experiments, pharmaceutical development of albicidin has been hampered by the fact that scientists did not know precisely how it interacted with DNA gyrase. (growkudos.com)
  • Now, Prof. Jonathan Heddle's research group at the Malopolska Centre of Biotechnology, Jagiellonian University, Poland alongside the laboratories of Prof. Roderich Süssmuth at Technische Universität Berlin, Germany and Dr. Dmitry Ghilarov at the John Innes Centre, UK have used advanced cryo-electron microscopy to obtain an unprecedentedly detailed snapshot of albicidin bound to gyrase. (growkudos.com)
  • The results were fascinating: albicidin forms an L-shape, enabling it to interact with both the gyrase and the DNA in a unique way. (growkudos.com)
  • DNA cleavage and reunion is performed by a catalytic center located in DNA-gates build by all gyrase subunits. (wikipedia.org)
  • The bactericidal effect is strong, but it is non-toxic, and it will not cause poisoning or other side effects if it exceeds the dosage several times. (ballyabio.com)
  • Desogestrel binds intracellular progesterone receptors in progesterone responsive tissue and the resultant complex interacts with DNA and results in either gene transcription or gene repression. (medindex.am)
  • Poison-antidote modules are found in natural plasmid in which they serve to the plasmid maintenance. (igem.org)
  • In theStaby TM system,the antidote gene (ccdA) is introduced in the plasmid DNA under the control of a weak constitutive promoter: the mob gene promoter, which originates from a broad host range plasmid (pBHR1). (igem.org)
  • Expression of the poison gene is under the control of a promoter strongly repressed in the presence of the plasmid. (igem.org)
  • A transposon refers to a chromosomal segment that can be translocated between chromosomal, plasmid or phage DNA. (pediaa.com)
  • Type I Topoisomerases act on one strand of double-stranded DNA, and they are further divided into three categories: IA, IB, and IC. (jove.com)
  • These amide NBTIs induced both single- and double-strand breaks in pBR322 DNA mediated by Staphylococcus aureus DNA gyrase, in contrast to prototypical NBTIs that cause only single-strand breaks. (bvsalud.org)
  • The DNA strand in E. coli contains about four million base pairs , and these base pairs are organized into about 1,000 genes . (howstuffworks.com)
  • The DNA strand contains the templates for all 1,000 enzymes that the bacterium needs to live its life. (howstuffworks.com)
  • This region covers both the catalytic core and the DNA-binding domains. (embl.de)
  • Transposons are called ' jumping genes ', and they can cause mutations and change in the amount of DNA in the genome. (pediaa.com)
  • This is dangerous, as broken DNA is lethal to the cell. (growkudos.com)
  • You can see that, in any living cell, DNA helps create enzymes, and enzymes create the chemical reactions that are 'life. (howstuffworks.com)
  • DNA is very tightly coiled in order to fit inside a cell. (vin.com)
  • Asexual populations of the human malaria parasite, Plasmodium falciparum, use a two-step genomic strategy to acquire accurate, beneficial DNA amplifications. (rathodlab.org)
  • Properties of Plasmodium falciparum with a Deleted Apicoplast DNA Gyrase. (rathodlab.org)
  • Additionally, supercoiling can occur when the DNA twists back on itself due to the inability of the DNA ends to freely rotate to relieve the torsional stress. (jove.com)
  • Together, these results demonstrate broad spectrum antibacterial properties of selected tricyclic NBTIs, desirable safety profiles, an unusual ability to induce DNA double-stranded breaks, and activity against human TOP2α. (bvsalud.org)
  • Most Type I topoisomerases do not require ATP to relax supercoiled DNA. (jove.com)
  • 23] [24] The Belgian company Delphi Genetics has developed a strategy called StabyTM system which relies on the use of poison-antidote genes. (igem.org)
  • These enzymes regulate positive and negative DNA supercoiling without changing the nucleotide sequence. (jove.com)
  • Type II topoisomerases, on the other hand, are ATP-dependent and act on supercoiled DNA where the DNA is tangled around itself. (jove.com)
  • An antibiotic is a poison that works to destroy bacterial cells while leaving human cells unharmed. (howstuffworks.com)
  • Brie﫿y, two single-stranded oligonucleotides are annealed to form a double-stranded DNA sequence containing the shRNA sequence followed by a Pol III terminator (consisting of a stretch of four or more thymidines), as well as 5'- and 3'-end "sticky" overhangs that are complementary to those generated in the targeting vector following restriction digestion with BglII and SalI (Figures 3E and 4C). (berterolab.com)
  • Transposition occurs in the absence of a complementary sequence in the host DNA. (pediaa.com)