Dna gyrase. Medical search. Frequent questions

Two classes of antibiotics that inhibit gyrase are: The aminocoumarins (including novobiocin and Coumermycin A1), which work by competitive inhibition of energy transduction of DNA gyrase by binding to the ATPase active site on the GyrB subunit. (wikipedia.org)
One of these hypothesis suggests the inhibition of subunit A of DNA-gyrase in presence of ATP [ 5 - 7 ]. (hindawi.com)

Thus, inhibition of the negative supercoiling activity of gyrase was the primary cause of enhanced DNA relaxation in drug-treated bacteria. (jic.ac.uk)
Staphylococcus aureus will be stopped by DNA gyrB inhibition. (biomedicineonline.org)
The molecular docking and MD simulation results revealed that compound 14 could act by inhibiting gyrase A. A pharmacophore model that consisted of the features that would help the inhibition effect was generated. (sdu.edu.tr)
Synthesis, antimicrobial evaluation, DNA gyrase inhibition, and in silico pharmacokinetic studies of novel quinoline derivatives. (olmdiagnostics.com)
Compounds that revealed the best activity were subjected to further biological studies to determine their minimum inhibitory concentrations (MICs) against the selected pathogens as well as their in vitro activity against the E. coli DNA gyrase, to realize whether their antimicrobial action is mediated via inhibition of this enzyme. (olmdiagnostics.com)
Several researches have been exhibited that mutations imparting fluoroquinolone resistance in P. aeruginosa may attributed to amendment in DNA gyrase, hypothesizing that faded sensitivity to fluoroquinolone result from inhibition of DNA supercoiling in resistant isolates of Gram-negative pathogens and alteration in gyrA consider leading causes in this resistance 7 . (microbiologyjournal.org)
Moxifloxacin inhibits the A subunits of DNA gyrase, resulting in inhibition of bacterial DNA replication and transcription. (medscape.com)
The effect on Escherichia coli is the inhibition of DNA synthesis through prevention of DNA supercoiling. (drugs.com)
Their bactericidal and bacteriostatic properties result from inhibition of the enzyme DNA gyrase. (aafp.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)
To address how gyrase copes with these topological challenges, we used high-speed single-molecule fluorescence imaging in live Escherichia coli cells. (york.ac.uk)
Using mass spectrometry, NMR spectroscopy, and fluorescence experiments we have demonstrated that compound 1 binds reversibly to the ATP-binding site of the 24 kDa N-terminal fragment of DNA gyrase B from Escherichia coli (GyrB24) with low micromolar affinity. (hal.science)
In this study, we investigated the presence of plasmid-mediated quinolone resistance (PMQR) genes among 101 ciprofloxacin-resistant urinary Escherichia coli isolates and searched for mutations in the quinolone-resistance-determining regions (QRDRs) of the DNA gyrase and topoisomerase IV genes in PMQR-carrying isolates. (scielo.br)

Hence, novel gyrase inhibitors with novel mechanisms are required. (sdu.edu.tr)
Objective: The aim of this study is to elucidate mode of action for existing DNA gyrase inhibitors and to pave the way towards discovery of novel inhibitors. (sdu.edu.tr)
Methods: In this study, the mechanism of action for selected DNA gyrase inhibitors available was carried out through molecular docking and molecular dynamics (MD) simulation. (sdu.edu.tr)
In addition, pharmacophore analysis, density functional theory (DFT) calculations, and computational pharmacokinetics analysis of the gyrase inhibitors were performed. (sdu.edu.tr)
Results: This study demonstrated that all the DNA gyrase inhibitors investigated, except compound 14, exhibit their activity by inhibiting gyrase B at a binding pocket. (sdu.edu.tr)
Conclusion: In this study, mode of action elucidation through molecular docking and MD simulation, pharmacophore model generation, pharmacokinetic property prediction, and DFT study for selected DNA gyrase inhibitors were carried out. (sdu.edu.tr)
The outcomes of this study are anticipated to contribute to the design of novel gyrase inhibitors. (sdu.edu.tr)
The predicted binding mode explains the competitive inhibitory mechanism with respect to ATP and forms a useful basis for further development of potent DNA gyrase inhibitors. (hal.science)
Herein, we report the synthesis and in vitro antimicrobial evaluation of novel quinoline derivatives as DNA gyrase inhibitors. (olmdiagnostics.com)
To understand the determinants of response to topoisomerase inhibitors, he is studying the repair pathway centered on tyrosyl-DNA-phosphodiesterases (TDP1 and TDP2) and poly(ADP-ribose)polymerases (PARP). (cancer.gov)
Dr. Pommier conceptualized the "interfacial inhibitors" mechanism based on his finding that DNA topoisomerase inhibitors act by trapping topoisomerase-DNA complexes (Capranico et al. (cancer.gov)
Quinolone carboxylic acid derivatives are classified as DNA gyrase inhibitors. (drugs.com)

They found out that green tea catechins inhibit essential bacterial enzyme DNA gyrase, which is the target of several existing clinically used drugs. (sciencedaily.com)

Ciprofloxacin inhibits bacterial DNA synthesis by binding to gyrase. (medscape.com)
It inhibits bacterial growth by inhibiting DNA gyrase. (medscape.com)
Levofloxacin inhibits DNA gyrase and topoisomerase IV, resulting in bactericidal activity. (medscape.com)
Inhibits bacterial DNA gyrase (topoisomerase). (enzolifesciences.com)
Thus, it seems that this protein binds to gyrase and inhibits its activity by mimicking DNA. (ne.jp)

In this study, the activity of medicinal compounds to inhibit DNA gyrB is explored. (biomedicineonline.org)
Phytochemical screening was performed to study the medication options that could inhibit DNA gyrB. (biomedicineonline.org)
Quinolones inhibit two enzymes that are required for bacterial DNA synthesis, i.e. (cdc.gov)
Inhibit DNA gyrase in bacterial cells. (flashcardmachine.com)
Quinolones inhibit the bacterial DNA synthesis [ 2 ], and there are several hypotheses to explain their mechanism of action. (hindawi.com)

The site of action is bacterial gyrase, a synthesis promoting enzyme. (drugs.com)
DNA Synthesis occurs during what phase of Mitosis? (flashcardmachine.com)
RNA and use it to synthesis DNA by reverse transcriptase. (flashcardmachine.com)

The targets of quinolone activity are the bacterial DNA gyrase and topoisomerase IV, enzymes essential for DNA replication and transcription. (cdc.gov)
Quinolones has the ability to sort kind two topoisomerases, which can be crucial compounds in arrange the topological condition of DNA via its replication and transcription. (microbiologyjournal.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)
E. coli DNA Gyrase, Topo IV, S. aureus DNA Gyrase, Topo IV TopoGEN offers powerful and tractable services to identify Gyrase and Topoisomerase IV targeting antibiotics. (topogen.com)
DNA gyrase and topoisomerase IV. (cdc.gov)
It functions by inhibiting DNA gyrase , a type II topoisomerase , and topoisomerase IV, [5] which is an enzyme necessary to separate, replicated DNA, thereby inhibiting cell division. (wikidoc.org)
Quinolone resistance among Enterobacteriaceae originally occurred due to chromosomal mutations in the quinolone-resistance-determining regions (QRDRs) of the gyrA and gyrB genes, which encode the gyrase A and B subunits, respectively and the parC and parE genes, which encode topoisomerase IV subunits (Hernández et al. (scielo.br)

The amino-terminal portion of the DNA gyrase B protein is thought to catalyze the ATP-dependent super-coiling of DNA. (nih.gov)
The carboxyl-terminal end supports the complexation with the DNA gyrase A protein and the ATP-independent relaxation. (nih.gov)
Therefore, molecular docking was also used in the present study to simulate the binding of cordycepin with different antibacterial targets, such as β-ketoacyl-(acyl-carrier-protein) synthase III (FabH), DNA gyrase B and thymidylate kinase, in order to identify the most likely antimicrobial mechanism of cordycepin. (spandidos-publications.com)
Streptomyces-produced quinolone and coumarin antibiotics, such as novobiocin, interfere with a protein called gyrase that assists in the normal separation of double-stranded DNA during replication of DNA or transcription of messenger RNA. (icr.org)
The CcdB protein (poison) is cytotoxic and poisons DNA-gyrase complexes. (igem.org)

Tse, Y.C., Wang, J.C. E. coli and M. luteus DNA topoisomerase I can catalyze catenation or decatenation of double-stranded DNA rings. (biomedicineonline.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)

DNA gyrase is a tetrameric enzyme that consists of 2 GyrA ("A") and 2 GyrB ("B") subunits. (wikipedia.org)
DNA cleavage and reunion is performed by a catalytic center located in DNA-gates build by all gyrase subunits. (wikipedia.org)
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 two regions correspond to DNA binding by C-terminal domains of GyrA subunits and resemble eukaryotic nucleosome binding motif. (wikipedia.org)

By a structure-based approach we have previously discovered compound 1, an indolinone derivative, possessing inhibitory activity against DNA gyrase. (hal.science)
A subsequent in vitro investigation against the bacterial DNA gyrase target enzyme revealed a significant potent inhibitory activity of quinoline derivative 14, which can be observed from its IC50 value (3.39 μM). (olmdiagnostics.com)

Which have ability to interfered with the bacterial DNA gyrase, it has bactericidal activity with a wide spectrum in opposition to Gram positive and Gram-negative microorganism 2 . (microbiologyjournal.org)

S. aureus Gyrase DNA Supercoiling Assay Plus includes 500 µl of 10 x Buffer T2, 410 µl of 10 x relaxed DNA, 22 µl of 1500 x H19 dye, 450 µl of 10 x ATP, 43 µl 7.5 uM S. aureus gyrase, 820 µl of 2 M potassium glutamate and 3000 µl of 10 x H19 dilution buffer. (assaydes.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)
The Salmonella cytosol reaches pH 5-6 in response to an external pH of 4-5: the ATP-dependent DNA supercoiling activity of purified gyrase was progressively inhibited by lowering the pH in this range, as was the ATP-dependent DNA relaxation activity of topo IV. (jic.ac.uk)
We propose that DNA relaxation in Salmonella within macrophage is due to acid-mediated impairment of the negative supercoiling activity of gyrase. (jic.ac.uk)
The research focuses on the discovery of novel plant-based therapeutic compounds to target DNA gyrase B activity. (biomedicineonline.org)
The goal of the study is to identify innovative plant-based medicinal molecules that specifically target DNA gyrase B activity. (biomedicineonline.org)
Also, a molecular docking study of the most active compounds was carried out to explore the binding affinity of the new ligands toward the active site of DNA gyrase enzyme as a proposed target of their activity. (olmdiagnostics.com)
by inhibiting the activity of DNA gyrase and topoisomerase, enzymes essential for bacterial DNA replication. (msdmanuals.com)

Wang, J.C. Cellular roles of DNA topoisomerases: a molecular perspective. (biomedicineonline.org)
The results of computational molecular docking analysis indicated that the interaction energy between cordycepin and NAD+‑dependent DNA ligase (LigA) was lower than that between cordycepin and other common antibacterial targets. (spandidos-publications.com)
Rapid molecular identification and typing methods that may be useful include 16S rRNA gene sequencing, random amplified polymorphic DNA and a combination polymerase chain reaction-restriction fragment length polymorphism analysis ( 39 , 116 ). (antimicrobe.org)
Molecular Evolution of the Pseudomonas aeruginosa DNA Gyrase gyrA Gene. (bvsalud.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)
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)
We demonstrate that at least 300 gyrase molecules are stably bound to the chromosome at any time, with ~12 enzymes enriched near each replication fork. (york.ac.uk)
Dwell times of ~2 s were observed for the dispersed gyrase molecules, which we propose maintain steady-state levels of negative supercoiling of the chromosome. (york.ac.uk)

Bacteria expressing novobiocin-resistant (NovR) derivatives of gyrase or topo IV also exhibited DNA relaxation at acid pH, although further relaxation with novobiocin was not seen in the strain with NovRgyrase. (jic.ac.uk)

Biophysical characterization of an indolinone inhibitor in the ATP-binding site of DNA gyrase. (hal.science)

RFLP-PCR showed that out of 17 isolates resistant to Ciprofloxacin mutation inDNA gyrase (GyrA) were detected in six (35.2 %) isolated while the reminder 11 (64.7%) has no mutation. (microbiologyjournal.org)

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)
DNA gyrase is a class of Type II Topoisomerases that plays an important role in bacterial viability. (biomedicineonline.org)
Topoisomerases are assuming crucial elements of DNA metabolism 5 . (microbiologyjournal.org)
He was the first to show that topoisomerases are trapped by DNA damage (by oxidative base lesions, base alkylation, DNA nicks) (Pourquier et al. (cancer.gov)
Recently, Dr. Pommier demonstrated that misincorporated ribonucleotides (the most frequent DNA alteration) trap topoisomerases, which convert them to toxic and mutagenic nicks by TOP1 (Kim et al. (cancer.gov)
2018). While studying the tyrosyl-DNA-phosphodiesterase (TDP1 and TDP2) repair pathways for the excision of topoisomerases from DNA, Dr. Pommier revealed that TDP1 repairs a broad range of 3'-blocking lesions in addition to TOP1 (Murai et al. (cancer.gov)

The ability of gyrase to relax positive supercoils comes into play during DNA replication and prokaryotic transcription. (wikipedia.org)
Bacterial DNA gyrase introduces negative supercoils into chromosomal DNA and relaxes positive supercoils introduced by replication and transiently by transcription. (york.ac.uk)
Removal of these positive supercoils is essential for replication fork progression and for the overall unlinking of the two duplex DNA strands, as well as for ongoing transcription. (york.ac.uk)
It is found in all bacteria and is involved in replication, repair, recombination, and DNA transcription. (biomedicineonline.org)
Dr. Pommier also discovered that the natural compound, ecteinascidin 743 (commercialized as Yondelis) and its analog trabectedin acts by alkylating DNA and killing cancer cells by trapping transcription-coupled nucleotide excision repair (TC-NER) (Takebayashi et al, Nature Med 2001). (cancer.gov)

It will be simpler to do a follow-up study on discovering bioactive compounds and evaluating their effectiveness in inhibiting DNA gyrB with the help of this preliminary data from the analytical procedures. (biomedicineonline.org)
Up to now several compounds targeted against the ATP-binding site of bacteria gyrase have been known but couldn't be used as drugs due to their side effects on mammalian cells. (sciencedaily.com)

Another hypothesis supports the existence of a cooperative bond between the quinolone-DNA-DNA-gyrase [ 8 - 11 ]. (hindawi.com)

This makes gyrase a good target for antibiotics. (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)

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)

Inhibiting ATP binding by DNA gyrase and topo IV with novobiocin enhanced the effect of low pH on DNA relaxation. (jic.ac.uk)

DNA Polymerase copies template in what direction? (flashcardmachine.com)
DNA polymerase has what kind of proofreading function? (flashcardmachine.com)

DNA gyrase is made from two A and B fragments, these fragments encoded through the gyrA and gyrB genes 4 . (microbiologyjournal.org)

Quinolones conflict with the motion of DNA gyrase, a critical bacterial kind II DNA topoisomerase 6 . (microbiologyjournal.org)

The study employs DNA gyrase as its target and provides information on potential therapeutic targets. (biomedicineonline.org)
DNA gyrase is a therapeutic target used in the design and development of new antibacterial agents. (sdu.edu.tr)

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 amino terminus of eukaryotic and prokaryotic DNA topoisomerase II are similar, but they have a different carboxyl terminus. (nih.gov)
Eukaryotic DNA polymerases? (flashcardmachine.com)

4] Failure of DNA to properly separate during these processes results in a bacterium not being able to divide normally or produce functional proteins. (icr.org)

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)

Strong gyrase binding sites (SGS) were found in some phages (bacteriophage Mu group) and plasmids (pSC101, pBR322). (wikipedia.org)

These species were validated primarily on the basis of DNA-DNA hybridization, 16S rRNA gene sequence analysis, antimicrobial susceptibility and biochemical profiles, and, to a lesser degree, on high-performance liquid chromatography ( 22 , 54 , 55 , 69 ). (antimicrobe.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)

The study focuses on DNA gyrase as a target and shows insights into future drug development. (biomedicineonline.org)
DNA gyrase represents a validated antibacterial target and has drawn much interest in recent years. (hal.science)
By the use of NMR spectroscopy, researchers from Slovenia have now pinpointed the ATP-binding site of DNA gyrase as target of EGCG, the most abundant catechin from the green tea extract. (sciencedaily.com)

DNA Repair 2020). (cancer.gov)

Prokaryotic DNA Polyermases? (flashcardmachine.com)

It contains two periodic regions in which GC-rich islands are alternated with AT-rich patches by a period close to the period of DNA double helix (≈10.5 bp). (wikipedia.org)
Results from circular dichroism and denaturation of calf thymus DNA (CT-DNA) suggested that increased amounts of copper complex were able to stabilize the double helix of DNA in vitro mainly by formation of hydrogen bonds between chn and the sugars of DNA minor groove. (hindawi.com)

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)

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)
Negative supercoiling of DNA by gyrase is inhibited in Salmonella enterica serovar Typhimurium during adaptation to acid stress. (jic.ac.uk)
Negative supercoiling of bacterial DNA by DNA gyr B is essential in replication which further influences all the metabolic activities. (biomedicineonline.org)

Anatomy1

Organisms14

Chemicals and Drugs50

Analytical, Diagnostic and Therapeutic Techniques and Equipment7

Phenomena and Processes19

Information Science3

Subunit2

Inhibition9

Escherichia4

Inhibitors12

Enzyme DNA gyrase1

Inhibits5

Inhibit5

Synthesis3

Replication and transcription2

Topoisomerase IV5

Protein5

Coli1

Superhelical1

Subunits4

Inhibitory activity2

Bactericidal activity1

Aureus1

Activity7

Molecular4

Molecules5

Derivatives1

Inhibitor1

Ciprofloxacin1

Topoisomerases6

Transcription5

Compounds2

Quinolone1

Antibiotics2

Positive supercoils2

Novobiocin1

Polymerase2

GyrB genes1

Quinolones1

Therapeutic2

Eukaryotic3

Proteins1

Complexes1

PBR3221

Antimicrobial1

Genes1

Target3

20201

Prokaryotic1

Double helix2

Occurs1

Negative4