difference between dna gyrase and topoisomerase

Most bacteria have two type IIA topoisomerases, DNA gyrase and topoisomerase IV. Generally, charge removal and a concomitant weakening of DNA wrapping lead to a decrease in supercoiling activities, but enhanced decatenation, and thus generated a more TopoIV-like enzyme. The MOST precise modern definition of a gene is a segment of genetic material that: A) codes for one polypeptide. DNA Replication In the following, we will dissect the role of the individual structural features of the CTD in determining the activities of gyrase and TopoIV. TopoIV relaxes positive supercoils much faster than negative supercoils (86,87). Without the GyrA-box, the tight connection between the first and last blade is missing, and the ParC CTD adopts an open, C-shaped structure with a gap between these blades (Figure 3D) (50,56). Type IIA topoisomerases include the eukaryotic topoisomerase II (TopoII) and the bacterial enzymes topoisomerase IV (TopoIV) and gyrase [reviewed in (7)]. Fluoroquinolones bind to enzymes DNA gyrase and topoisomerase IV, preventing bacterial DNA replication. showed that mutations of positive charges in different blades of TopoIV have differential effects on the interaction of TopoIV with different DNA substrate, and on different activities of TopoIV. Influence of activity in the absence of direct physical interaction between DNA transaction proteins is another important means of modulation. This balance is the result of less efficient DNA supercoiling compared to other gyrases; the decatenation activity remains lower than the one of TopoIV (124,125). As a result of this rotation, the ATPase domain of one protomer comes into close contact with the DNA cleavage part of the second protomer (65). Related to this mechanism of action, bacteria have developed resistance mechanisms consisting in some target mutations (GyrA/GyrB for DNA gyrase and ParC/ParE for topoisomerase IV) or in a reduced access to the target itself, by The upper part shows the canonical strand-passage mechanism for DNA supercoiling, depicting gyrase in top view, looking down in the DNA bound at the DNA-gate. WebWai Mun Huang, in Advances in Pharmacology, 1994. Despite their well-separated cellular functions, gyrase and TopoIV have an overlapping activity spectrum: gyrase is also able to catalyze DNA decatenation, although less efficiently than TopoIV. In E.coli gyrase, the C-tail acts as an auto-inhibitory element: the E.coli CTD and the GyrA subunit are not able to bind DNA or to introduce writhe, but gain these functions when the C-tail is removed (63). The ATP-dependent relaxation activity of gyrase lacking the CTDs also depends on double-strand cleavage and strand passage (84). This enzyme needs to remove positive supercoils ahead of the replication fork and decatenate replication intermediates in vivo. DNA gyrase unlinks replicating DNA by introducing negative supercoils while Topo IV decatenates the two daughter molecules. Most of this displacement, enabled by a conserved proline in a -strand of blade 2 occurs between blades 1 and 2 (62). Corbett K.D., Shultzaberger R.K., Berger J.M. Vos S.M., Tretter E.M., Schmidt B.H., Berger J.M. A slower DNA cleavage step then occurs, A nonconserved acidic C-terminal tail modulates, The acidic C-terminal tail of the GyrA subunit moderates the DNA supercoiling activity of Bacillus subtilis gyrase, Structure of a topoisomerase II-DNA-nucleotide complex reveals a new control mechanism for ATPase activity, Structure of an openclamp type II topoisomerase-DNA complex provides a mechanism for DNA capture and transport, Structural insight into negative DNA supercoiling by DNA gyrase, a bacterial type 2A DNA topoisomerase, Structural insights into the quinolone resistance mechanism of, DNA gyrase and its complexes with DNA: direct observation by electron microscopy, Small-angle X-ray scattering reveals the solution structure of the full-length DNA gyrase a subunit, Guiding strand passage: DNA-induced movement of the gyrase C-terminal domains defines an early step in the supercoiling cycle, Distinct regions of the Escherichia coli ParC C-terminal domain are required for substrate discrimination by topoisomerase IV, Moving one DNA double helix through another by a type II DNA topoisomerase: the story of a simple molecular machine, Structural basis of gate-DNA breakage and resealing by type II topoisomerases, The DNA dependence of the ATPase activity of DNA gyrase, Structure of the DNA gyrase-DNA complex as revealed by transient electric dichroism, Binding of two DNA molecules by type II topoisomerases for decatenation, DNA gyrase action involves the introduction of transient double-strand breaks into DNA, Probing the two-gate mechanism of DNA gyrase using cysteine cross-linking, Binding and hydrolysis of a single ATP is sufficient for N-gate closure and DNA supercoiling by gyrase, DNA gyrase with a single catalytic tyrosine can catalyze DNA supercoiling by a nicking-closing mechanism, Why two? Mycobacterial gyrase can thus be regarded as an evolutionary compromise to perform both tasks. Their common catalytic principle consists of the cleavage of one or two DNA strands, the manipulation of topology, and the resealing of the gap in the DNA strand(s) [reviewed in (6)]. In gram-negative bacteria the fluoroquinolones must first cross the outer membrane. On binding, the G-segment becomes bent (dark blue) at the DNA-gate, and is wrapped around the CTD (green). Deletion of the entire CTD, mutation of a conserved motif and even by just a single point mutation within the CTD converts gyrase into a TopoIV-like enzyme, implicating the CTDs as the major determinant for function. It is conceivable that topoisomerase subunits were present even during the RNA world, and then jointly took over different functions later on (128). The GyrA-box in blade 1 of the CTD was discovered as a signature motif of gyrases (57,105). Finally, FtsK interacts with ParC, leading to an increased concentration of TopoIV at the septal ring, where it decatenates newly replicated chromosomes prior to segregation (114). DNA gyrase and topoisomerase IV are the targets for many antibiotics that, according to their mechanism of action, may be divided into two groups: poisons and catalytic inhibitors. Among the four topoisomerases identified in eubacteria, two, DNA gyrase and topoisomerase IV have been exploited by nature and the pharmaceutical industry as antibacterial targets. DNA Topoisomerase (ATP Hydrolysing In contrast, the influence on purified mammalian DNA enzymes, including topoisomerases, has been reported to be several orders of magnitude weaker, oc Differential behaviors of Staphylococcus aureus and Escherichia Stabilizes single-stranded DNA. In contrast, TopoIV is located on the negatively supercoiled DNA behind the replication fork, where its decatenation activity is stimulated (16,17,86,87,89). The TOPRIM domains are in a similar orientation as in gyrase, but the ParE ATPase domains are bent downwards, facing toward the C-gate, and are far apart from each other. In this reaction, the catalytic tyrosines in GyrA/ParC act as nucleophiles; they remain covalently bound to the 5-end of each DNA strand (81). WebFor many years, DNA gyrase was thought to be responsible both for unlinking replicated daughter chromosomes and for controlling negative superhelical tension in bacterial Topoisomerase Since that time, further study identified two bacterial topoisomerases, DNA gyrase and topoisomerase IV, as sites of antibacterial activity DNA gyrase appears to be the primary quinolone target for gram-negative bacteria. Residues on blades 2 and 3 determine the processivity of relaxation and decatenation. The processivity difference has been ascribed to a more stable interaction of TopoIV CTDs with the DNA during relaxation of positively supercoiled DNA, leading to a lower rate constant for dissociation of the enzyme from positively than from negatively supercoiled DNA (50,75,87). Non-quinolone Topoisomerase Inhibitors The ATP-operated clamp inhibits the rotation of the T-segment around its helical axis. Manage alerts. Acidic residues in the C-terminal tail are depicted in red. We show here that single strand binding protein stimulates DNA topoisomerase I activity without direct protein-protein interactions. re-constituted a gyrase-like enzyme with supercoiling activity by mixing E.coli GyrA and A. aeolicus ParE (58). These observations suggest an alternative mechanism for supercoiling, in which two positive supercoils are captured by gyrase, segregated from the rest of the substrate, and relaxed by nicking of one of the strands (Figure 5) (84). In this configuration, blade 1 is the last blade that is contacted by the wrapped DNA before it exits the CTD (68). For many years, DNA gyrase was thought to be responsible both for unlinking replicated daughter chromosomes and for controlling negative superhelical tension in bacterial DNA. DNA gyrase consists of two copies of GyrA and two copies of GyrB and functions as an A 2 B 2 heterotetramer (Fig. Examples of type IIA topoisomerases include eukaryotic topo II, E. coli gyrase, and E. coli topo IV. Weba. The important role of the CTDs in DNA binding to gyrase became evident from DNase- and hydroxyl-radical footprinting experiments: full-length gyrase protects a 140bp-DNA segment, with a higher protection of the central 40bp (60,98102). This variant supercoils DNA with similar characteristics as the wildtype enzyme, introducing changes of the linking number in steps of two and undergoing the same conformational changes in the catalytic cycle (84). Lessons in drug discovery and development: a critical analysis of more than 50 years of effort toward ATPase inhibitors of DNA gyrase and topoisomerase IV, Targeting bacterial topoisomerases: how to counter mechanisms of resistance, Crystal structure of DNA gyrase B domain sheds lights on the mechanism for T-segment navigation, Crystal structure of the breakage-reunion domain of DNA gyrase, The C-terminal domain of the Escherichia coli DNA gyrase A subunit is a DNA-binding protein, The C-terminal domain of DNA gyrase A adopts a DNA-bending -pinwheel fold, DNA transport by a type II DNA topoisomerase: evidence in favor of a two-gate mechanism, DNA transport by a type II topoisomerase: direct evidence for a two-gate mechanism, The path of the DNA along the dimer interface of topoisomerase II, DNA-induced narrowing of the gyrase N-gate coordinates T-segment capture and strand passage, Probing the role of the ATP-operated clamp in the strand-passage reaction of DNA gyrase, Locking the ATP-operated clamp of DNA gyrase: probing the mechanism of strand passage, Trapping of the transport-segment DNA by the ATPase domains of a type II topoisomerase, Structural basis for gate-DNA recognition and bending by type IIA topoisomerases, Structure and mechanism of DNA topoisomerase II, Crystal structure of an N-terminal fragment of the DNA gyrase B protein, Functional interactions between gyrase subunits are optimized in a species-specific manner, Tricyclic GyrB/ParE (TriBE) inhibitors: a new class of broad-spectrum dual-targeting antibacterial agents, Crystal structures of the 43 kDa ATPase domain of, The structural basis for substrate specificity in DNA topoisomerase IV, Crystallization and preliminary X-ray diffraction analysis of two N-terminal fragments of the DNA-cleavage domain of topoisomerase IV from Staphylococcus aureus. WebWe would like to show you a description here but the site wont allow us. As a result, the enzyme is also a gyrase with respect to its preference for positively supercoiled DNA substrates (91). From the appreciable level of sequence conservation, the shared domain architecture and similar structures of individual domains or sub-domains (28,30,37,43,50,66), an overall structure similar to TopoII has been inferred for gyrase and TopoIV heterotetramers. Chapter 10 Study Guide Hsiehetal. With its multiple cellular functions, in the maintenance of supercoiling homeostasis, and in transcription and replication, gyrase appears to be the more important enzyme of the two. DNA Topoisomerase IV makes a type IIA topoisomerase a gyrase or The close relation of gyrase and TopoIV is also evidenced by their shared sensitivity to coumarin and quinolone inhibitors (120,129). WebHelicases are enzymes that separate the nucleic acid strands for replication. The preferential relaxation of positive supercoils by TopoIV and the conversion of positive into negative supercoils by gyrase jointly remove excess positive supercoils in bacteria without relaxation of negative supercoiling required for DNA compaction and metabolism. named this structure a hairpin-invaded -propeller (56), and compared the connection between adjacent blades achieved by the strand exchange to a Velcro system. Topoisomerase as target for antibacterial and anticancer Although these three enzymes share a highly similar core structure, they catalyze different reactions in vitro, and fulfil different tasks in the cell (Figure 1): TopoII catalyzes the ATP-dependent relaxation of positive and negative supercoils in the presence of ATP (8). This enzyme cleaves only a single strand of the G-segment, but still catalyzes supercoiling in steps of two (84). We have demonstrated that deletion of the Abstract. Three well-examined interaction partners of TopoIV are MukB, SeqA,and FtsK. III Bacterial Topoisomerase IV Genes. The differential engagement of the CTDs with different substrates, and their contributions to G-segment bending and T-segment binding, require a reorientation of the CTDs relative to the NTD (75) that has not been probed experimentally. Gyrase and TopoIV share similar structures, but have different substrate preferences and perform different cellular activities, which raises the question: What makes a type IIA topoisomerase a gyrase or a TopoIV?
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