Discuss tworeasons why inhibiting DNA gyrase also inhibits bacterial growth Coumarins and quinolones are two classes of drugs that inhibitbacterial growth by directly inhibiting DNA gyrase. Discuss tworeasons why inhibiting DNA gyrase also inhibits bacterial growth
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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....DNA gyrase.SearchPubMedarticlesNCBIproteins1 more row
4.2. DNA gyrase inhibitors of synthetic origin. Fluoroquinolones have been the most successful antibacterial agents targeting DNA gyrase. These compounds have been extensively explored and researched to improve spectrum of activity, potency and bacterial resistance.
Ultimate denaturation or disruption of gyrase in ternary complex results in the generation of DSB and thereby replication blockage and cell death (10, 11). Mutations in either gyrA or gyrB cause quinolone resistance.
DNA Gyrase - This enzyme catalyzes the formation of negative supercoils that is thought to aid with the unwinding process. In addition to these proteins, several other enzymes are involved in bacterial DNA replication.
Quinolones, coumarins, cyclothialidines, CcdB and microcin B17 inhibit DNA gyrase. Information regarding these various inhibitors comes from studies performed with the enzyme from Escherichia coli, and subsequent analyses have also primarily been confined to this system.
Other processes affect DNA topology as well – including DNA replication and transcription (24). Without gyrase, which regulates DNA topology by introducing negative supercoils and relieving excess positive supercoils ahead of replication forks (25, 26), replication cannot proceed (27, 28).
QuinolonesQuinolones are a key group of antibiotics that interfere with DNA synthesis by inhibiting topoisomerase, most frequently topoisomerase II (DNA gyrase), an enzyme involved in DNA replication.
DNA gyrase (also referred to as topoisomerase) reduces supercoiling (relaxes tension) which builds up during DNA unwinding, preventing DNA breakage.
Quinolones dually target DNA gyrase and topoisomerase IV binding to specific domains and conformations so as to block DNA strand passage catalysis and stabilize DNA–enzyme complexes that block the DNA replication apparatus and generate double breaks in DNA that underlie their bactericidal activity.
In principle, eukaryotes do not require gyrase because negative supercoiling can be established by the wrapping of DNA around histones and the relaxation of the internucleosomal DNA by topos I and II; topo II is evolutionarily related to gyrase but lacks the ability to supercoil DNA (1).
DNA gyrase introduces supercoils, and DNA topoisomerase I prevents supercoiling from reaching unacceptably high levels. Perturbations of supercoiling are corrected by the substrate preferences of these topoisomerases with respect to DNA topology and by changes in expression of the genes encoding the enzymes.
How would DNA replication be affected in a bacterial cell that is lacking DNA gyrase? Topoisomerase II or gyrase reduces the positive supercoiling or torsional strain that develops ahead of the replication fork due to the unwinding of the double helix.
If DNA replication was inhibited, the bacteria could not grow and divide into new daughter cells. As discussed in Chapter 12, gene transcription is necessary for bacterial cells to make proteins. If gene transcription was inhibited, the bacteria could not make many proteins that are necessary for survival.
Loops of DNA are anchored to DNA-binding proteins to form smaller microdomains, and these microdomains are found within larger macrodomains. Secondly, the DNA double helix is supercoiled to make it more compact, much like twisting a rubber band.
Also, because negative supercoiling aids in strand separation, these drugs would make it more difficult for the DNA strands to separate. Therefore, the bacteria would have a difficult time transcribing their genes and replicating their DNA , because both processes require strand separation.
Negative supercoiling is needed to compact the chromosomal DNA, and it also aids in strand separation. Bacteria might not be able to survive and/or transmit their chromosomes to daughter cells if their DNA was not compacted properly.
Click card to see definition 👆. Tap card to see definition 👆. The bacterial nucleoid is a region in a bacterial cell that contains a compacted circular chromosome. Unlike the eukaryotic nucleus, a nucleoid is not surrounded by a membrane. Click again to see term 👆.
Therefore, a segment of DNA could be derived from 2 or more nucleosomes and would be in multiples of 200 bp.
A helix is a coiled structure. Supercoiling involves adding coiling to a structure that is already a coil. Positive supercoiling is called overwinding because it adds additional twists in the same direction as the DNA double helix is already coiled, which is the right-handed direction.