topoisomerase IV
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Topoisomerase IV is one of two
Type II topoisomerase Type II topoisomerases are topoisomerases that cut both strands of the DNA helix simultaneously in order to manage DNA tangles and supercoils. They use the hydrolysis of ATP, unlike Type I topoisomerase. In this process, these enzymes change th ...
s in bacteria, the other being
DNA gyrase 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-poly ...
. Like gyrase, topoisomerase IV is able to pass one double-strand of DNA through another double-strand of DNA, thereby changing the
linking number In mathematics, the linking number is a numerical invariant that describes the linking of two closed curves in three-dimensional space. Intuitively, the linking number represents the number of times that each curve winds around the other. In E ...
of DNA by two in each enzymatic step. Both share a hetero-4-mer structure formed by a symmetric homodimer of A/B heterodimers, usually named ''ParC'' and ''ParE''.


Functions

Topoisomerase IV has two functions in the cell. * First, it is responsible for unlinking, or decatenating, DNA following
DNA replication In molecular biology, DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule. DNA replication occurs in all living organisms acting as the most essential part for biological inheritan ...
. The double-helical nature of DNA and its
semiconservative Semiconservative replication describe the mechanism of DNA replication in all known cells. DNA replication occurs on multiple origins of replication along the DNA template strand (antinsense strand). As the DNA double helix is unwound by helicas ...
mode of replication causes the two newly replicated DNA strands to be interlinked. These links must be removed in order for the
chromosome A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins ar ...
(and
plasmids A plasmid is a small, extrachromosomal DNA molecule within a cell that is physically separated from chromosomal DNA and can replicate independently. They are most commonly found as small circular, double-stranded DNA molecules in bacteria; how ...
) to segregate into daughter cells so that cell division can complete. * Topoisomerase IV's second function in the cell is to relax positive
supercoil DNA supercoiling refers to the amount of twist in a particular DNA strand, which determines the amount of strain on it. A given strand may be "positively supercoiled" or "negatively supercoiled" (more or less tightly wound). The amount of a st ...
s. It shares this role with DNA gyrase, which is also able to relax positive supercoils. Together, gyrase and topoisomerase IV remove the positive supercoils that accumulate ahead of a translocating
DNA polymerase A DNA polymerase is a member of a family of enzymes that catalyze the synthesis of DNA molecules from nucleoside triphosphates, the molecular precursors of DNA. These enzymes are essential for DNA replication and usually work in groups to crea ...
, allowing
DNA replication In molecular biology, DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule. DNA replication occurs in all living organisms acting as the most essential part for biological inheritan ...
to continue unhindered by topological strain. *
DNA gyrase 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-poly ...
s are analogous enzymes in other organisms. While topoisomerase IV does relax positive supercoils like DNA gyrase, it does not introduce further negative supercoiling like the latter enzyme. Topoisomerase IV can unknot right-handed knots and decatenate right-handed catenanes without acting on right-handed plectonemes in negatively supercoiled DNA molecules, based on geometrical specificity of juxtapositions.


Clinical significance

Topoisomerase IV is also a target of
antibiotics An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and preventio ...
, such as the
quinolone Quinolone may refer to: * 2-Quinolone * 4-Quinolone * Quinolone antibiotic A quinolone antibiotic is a member of a large group of broad-spectrum bacteriocidals that share a bicyclic core structure related to the substance 4-quinolone. They a ...
drugs, which include
ciprofloxacin Ciprofloxacin is a fluoroquinolone antibiotic used to treat a number of bacterial infections. This includes bone and joint infections, intra abdominal infections, certain types of infectious diarrhea, respiratory tract infections, skin i ...
.


References


External links

* EC 5.99.1 {{enzyme-stub