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the 4th letter of the Roman alphabet (同)d

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deuteriumの化学記号
deoxyribonucleic acidディオキシリボ核酸

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/03/11 13:14:56」(JST)

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DNA gyrase, often referred to simply as gyrase, is an enzyme that relieves strain while double-stranded DNA is being unwound by helicase. This causes negative supercoiling of the DNA. Bacterial DNA gyrase is the target of many antibiotics, including nalidixic acid, novobiocin, and ciprofloxacin.

DNA gyrase is a type II topoisomerase (EC 5.99.1.3) that introduces negative supercoils (or relaxes positive supercoils) into DNA by looping the template so as to form a crossing, then cutting one of the double helices and passing the other through it before releasing the break, changing the linking number by two in each enzymatic step. This process occurs in prokaryotes (in particular, in bacteria), whose single circular DNA is cut by DNA gyrase and the two ends are then twisted around each other to form supercoils. Very recently, gyrase has been found in the apicoplast of the malarial parasite Plasmodium falciparum, a unicellular eukaryote.

The unique ability of gyrase to introduce negative supercoils into DNA is what allows bacterial DNA to have free negative supercoils. The ability of gyrase to relax positive supercoils comes into play during DNA replication. The right-handed nature of the DNA double helix causes positive supercoils to accumulate ahead of a translocating enzyme, in the case of DNA replication, a DNA polymerase. 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.

Mechanochemical model of gyrase activity

A single molecule study^[1] has characterized gyrase activity as a function of DNA tension (applied force) and ATP, and proposed a mechanochemical model. Upon binding to DNA (the "Gyrase-DNA" state), there is a competition between DNA wrapping and dissociation, where increasing DNA tension increases the probability of dissociation. Upon wrapping and ATP hydrolysis, two negative supercoils are introduced into the template, providing opportunities for subsequent wrapping and supercoiling events.

Inhibition by antibiotics

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. It is not present in humans. This makes gyrase a good target for antibiotics. Two classes of antibiotics that inhibit gyrase are:

The aminocoumarins (including novobiocin). Aminocoumarins work by competitive inhibition of energy transduction of DNA gyrase by binding to the ATPase active site located on the GyrB subunit.
The quinolones (including nalidixic acid and ciprofloxacin). Quinolones bind these enzymes and prevent them from decatenating replicating DNA. Quinolone-resistant bacteria frequently harbor mutated topoisomerases that resist quinolone binding.

Notes

^ Gore J, Bryant Z, Stone MD, Nollmann M, Cozzarelli NR, Bustamante C, "Mechanochemical Analysis of DNA Gyrase Using Rotor Bead Tracking", Nature 2006 Jan 5 (Vol. 439): 100-104.

DNA gyrase has two subunits,which in turn have two subunits each,ie 2A and 2B SUBUNITS.The A subunit carries out nicking of DNA,B subunit introduces negative supercoils,and then A subunit reseals the strands.Fluorquinolones bind to the A subunit and interfere with its strand cutting and resealing function.

References

Molecular Cloning of Apicoplast-Targeted Plasmodium falciparum DNA Gyrase Genes: Unique Intrinsic ATPase Activity
ATP-Independent Dimerization of PfGyrB Subunit.(2007)EUKARYOTIC CELL, Mar. 2007, p. 398–412

UpToDate Contents

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1. フルオロキノロン類 fluoroquinolones
2. 薬剤耐性結核の疫学および分子メカニズム epidemiology and molecular mechanisms of drug resistant tuberculosis
3. 腸炎エルシニアおよび偽結核菌感染症の治療および予防 treatment and prevention of yersinia enterocolitica and yersinia pseudotuberculosis infection
4. アエロモナス感染症 aeromonas infections
5. ハンセン病の治療および予防 treatment and prevention of leprosy

English Journal

E. coli Gyrase Fails to Negatively Supercoil Diaminopurine-Substituted DNA.

Fernández-Sierra M1, Shao Q1, Fountain C1, Finzi L1, Dunlap D2.
Journal of molecular biology.J Mol Biol.2015 Jul 3;427(13):2305-18. doi: 10.1016/j.jmb.2015.04.006. Epub 2015 Apr 19.
Type II topoisomerases modify DNA supercoiling, and crystal structures suggest that they sharply bend DNA in the process. Bacterial gyrases are a class of type II topoisomerases that can introduce negative supercoiling by creating a wrap of DNA before strand passage. Isoforms of these essential enzy
PMID 25902201

Antimicrobial mechanism of resveratrol-trans-dihydrodimer produced from peroxidase-catalyzed oxidation of resveratrol.

Mora-Pale M1, Bhan N1, Masuko S2, James P3, Wood J2, McCallum S4, Linhardt RJ1,2,5,6, Dordick JS1,4,5,7, Koffas MA1,5.
Biotechnology and bioengineering.Biotechnol Bioeng.2015 Jun 24. doi: 10.1002/bit.25686. [Epub ahead of print]
Plant polyphenols are known to have varying antimicrobial potencies, including direct antibacterial activity, synergism with antibiotics and suppression of bacterial virulence. We performed the in vitro oligomerization of resveratrol catalyzed by soybean peroxidase, and the two isomers (resveratrol-
PMID 26109045

The Albicidin Resistance Factor AlbD Is a Serine Endopeptidase That Hydrolyzes Unusual Oligoaromatic-Type Peptides.

Vieweg L1, Kretz J1, Pesic A1, Kerwat D1, Grätz S1, Royer M2, Cociancich S2, Mainz A1, Süssmuth RD1.
Journal of the American Chemical Society.J Am Chem Soc.2015 Jun 24;137(24):7608-11. doi: 10.1021/jacs.5b04099. Epub 2015 Jun 15.
The para-aminobenzoic acid-containing peptide albicidin is a pathogenicity factor synthesized by Xanthomonas albilineans in infections of sugar cane. Albicidin is a nanomolar inhibitor of the bacterial DNA gyrase with a strong activity against various Gram-negative bacteria. The bacterium Pantoea di
PMID 26057615

Japanese Journal

Impact of Amino Acid Substitutions in B Subunit of DNA Gyrase in Mycobacterium leprae on Fluoroquinolone Resistance

Yokoyama Kazumasa,Kim Hyun,Mukai Tetsu,Matsuoka Masanori,Nakajima Chie,Suzuki Yasuhiko
PLoS Neglected Tropical Diseases 6(10), 1838, 2012-10-11
… FQs are known to interact with both A and B subunits of DNA gyrase and inhibit supercoiling activity of this enzyme. … leprae, we examined the inhibitory activity of FQs against recombinant DNA gyrases with amino acid substitutions at position 464, 502 and 504, equivalent to position 461, 499 and 501 in M. … Additionally, effectiveness of sitafloxacin, a FQ, to mutant DNA gyrases was revealed by low inhibitory concentration of this FQ. …
NAID 120004979565

Contribution of the AcrAB-TolC Efflux Pump to High-Level Fluoroquinolone Resistance in Escherichia coli Isolated from Dogs and Humans

SATO Toyotaka,YOKOTA Shin-ichi,OKUBO Torahiko,ISHIHARA Kanako,UENO Hiroshi,MURAMATSU Yasukazu,FUJII Nobuhiro,TAMURA Yutaka
Journal of Veterinary Medical Science, 2012
… Fluoroquinolone resistance is mainly caused by mutations in quinolone resistance-determining regions of DNA gyrase and topoisomerase IV in Escherichia coli. …
NAID 130002502179