DNA gyrase, often referred to simply as gyrase, is an enzyme that relieves strain while double-strand 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. It 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 and prokaryotic transcription. 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.
A single molecule study 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.
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 quinolones (including nalidixic acid and ciprofloxacin). Quinolones bind to these enzymes and prevent them from decatenation replicating DNA. Quinolone-resistant bacteria frequently harbor mutated topoisomerases that resist quinolone binding.
DNA gyrase has two subunits, which in turn have two subunits each, i.e. 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.
^Morais Cabral, J. H.; Jackson, A. P.; Smith, C. V.; Shikotra, N; Maxwell, A; Liddington, R. C. (1997). "Crystal structure of the breakage-reunion domain of DNA gyrase". Nature388 (6645): 903–6. doi:10.1038/42294. PMID9278055.
^Molecular Cloning of Apicoplast-Targeted Plasmodium falciparum DNA Gyrase Genes: Unique Intrinsic ATPase Activity and ATP-Independent Dimerization of PfGyrB Subunit.(2007) EUKARYOTIC CELL, Mar. 2007, p. 398–412
^A unique 45 amino acid region in the Toprim domain of Plasmodium falciparum GyraseB is essential for its activity.(2009)Eukaryotic Cell,11(8), 1759-69.