DNA gyrase

DNA gyrase

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 and novobiocin.

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 reported from the apicoplast of malarial parasite Plasmodium falciparum (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.

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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

  1. ^ 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.

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

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См. также в других словарях:

  • DNA gyrase — DNA gyrase. См. ДНК гираза. (Источник: «Англо русский толковый словарь генетических терминов». Арефьев В.А., Лисовенко Л.А., Москва: Изд во ВНИРО, 1995 г.) …   Молекулярная биология и генетика. Толковый словарь.

  • DNA gyrase — DNR girazė statusas T sritis chemija apibrėžtis Fermentas, katalizuojantis superspiralinės DNR susidarymą esant ATP. atitikmenys: angl. DNA gyrase rus. ДНК гираза …   Chemijos terminų aiškinamasis žodynas

  • DNA gyrase — DNA gy·rase (jiґrās) DNA topoisomerase (ATP hydrolyzing) …   Medical dictionary

  • DNA gyrase — A type II topoisomerase of Escherichia coli, that is essential for DNA replication. This enzyme can induce or relax supercoiling …   Dictionary of molecular biology

  • Gyrase — DNA Gyrase Enzymklassifikation EC, Kategorie …   Deutsch Wikipedia

  • DNA replication — DNA replication. The double helix is unwound and each strand acts as a template for the next strand. Bases are matched to synthesize the new partner strands. DNA replication is a biological process that occurs in all living organisms and copies… …   Wikipedia

  • DNA ligase — repairing chromosomal damage Identifiers EC number 6.5.1.1 …   Wikipedia

  • DNA polymerase delta — is an enzyme complex found in eukaryotes that is involved in DNA replication and repair, and it consists of the proliferating cell nuclear antigen (PCNA), the multisubunit replication factor C, and the 4 subunit polymerase complex: POLD1, POLD2,… …   Wikipedia

  • gyrase — gyrase. = DNA gyrase (см.). (Источник: «Англо русский толковый словарь генетических терминов». Арефьев В.А., Лисовенко Л.А., Москва: Изд во ВНИРО, 1995 г.) …   Молекулярная биология и генетика. Толковый словарь.

  • DNA topoisomerase (ATP-hydrolyzing) — DNA topo·isom·er·ase (ATP hy·dro·lyz·ing) (to″po i somґər ās hiґdro li zing) [EC 5.99.1.3] an enzyme of the isomerase class that catalyzes the ATP dependent breakage, passage, and rejoining of both strands of a DNA helix… …   Medical dictionary


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