In front of and behind the replication fork: bacterial type IIA topoisomerases

Sissi, Claudia; Palumbo, Manlio

doi:10.1007/s00018-010-0299-5

Cited by 78 publications

(78 citation statements)

References 189 publications

(247 reference statements)

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“…Ectopic expression of GyrB both of E. coli or B. schoenbuchensis unambiguously showed that these proteins are adenylylated by VbhT in bacterial lysates in vitro ( Figure 2D). Given the very high similarity in sequence, structure, and function to GyrB, we further suspected that its paralog ParE also might be targeted by VbhT (Sissi and Palumbo, 2010). Indeed, like for GyrB, ectopic expression of ParE of E. coli and B. schoenbuchensis clearly demonstrated adenylylation by VbhT ( Figure 2D).…”

Section: Ectopic Expression Of Diverse Ficts Results In Reversible Inmentioning

confidence: 90%

“…GyrB and ParE are the B subunits of the two bacterial type IIA topoisomerases DNA gyrase and topo IV that control cellular DNA topology by maintaining negative supercoiling and removing DNA catenation and knotting, respectively (Sissi and Palumbo, 2010). Therefore, their activities are generally essential for all processes in bacterial cells that involve the manipulation of closed circular DNA, such as chromosome replication, segregation, and transcription (Vos et al, 2011).…”

Section: Ectopic Expression Of Diverse Ficts Results In Reversible Inmentioning

confidence: 99%

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Adenylylation of Gyrase and Topo IV by FicT Toxins Disrupts Bacterial DNA Topology

et al. 2015

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Toxin-antitoxin (TA) modules are ubiquitous molecular switches controlling bacterial growth via the release of toxins that inhibit cell proliferation. Most of these toxins interfere with protein translation, but a growing variety of other mechanisms hints at a diversity that is not yet fully appreciated. Here, we characterize a group of FIC domain proteins as toxins of the conserved and abundant FicTA family of TA modules, and we reveal that they act by suspending control of cellular DNA topology. We show that FicTs are enzymes that adenylylate DNA gyrase and topoisomerase IV, the essential bacterial type IIA topoisomerases, at their ATP-binding site. This modification inactivates both targets by blocking their ATPase activity, and, consequently, causes reversible growth arrest due to the knotting, catenation, and relaxation of cellular DNA. Our results give insight into the regulation of DNA topology and highlight the remarkable plasticity of FIC domain proteins.

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Section: Ectopic Expression Of Diverse Ficts Results In Reversible Inmentioning

confidence: 90%

Section: Ectopic Expression Of Diverse Ficts Results In Reversible Inmentioning

confidence: 99%

Adenylylation of Gyrase and Topo IV by FicT Toxins Disrupts Bacterial DNA Topology

et al. 2015

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“…ATP binding to the ATPase domain of the GyrB subunit causes N-gate closing and ensures directional transfer of the trapped DNA T-segment through the DNA-gate. Closure of the N-gate may also exert a pinching force that is mediated by the transducer domains on the trapped DNA segment to facilitate transfer through the DNA-gate [3]. It has been demonstrated that ATP hydrolysis occurs sequentially for yeast topoisomerase II [29].…”

Section: Discussionmentioning

confidence: 99%

“…For clarity, the coiled-coil and β-pinwheel domains of GyrA are omitted in (b-d). Adopted from references [3], [5].…”

Section: Introductionmentioning

confidence: 99%

Structure of the N-Terminal Gyrase B Fragment in Complex with ADP⋅Pi Reveals Rigid-Body Motion Induced by ATP Hydrolysis

2014

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Type II DNA topoisomerases are essential enzymes that catalyze topological rearrangement of double-stranded DNA using the free energy generated by ATP hydrolysis. Bacterial DNA gyrase is a prototype of this family and is composed of two subunits (GyrA, GyrB) that form a GyrA2GyrB2 heterotetramer. The N-terminal 43-kDa fragment of GyrB (GyrB43) from E. coli comprising the ATPase and the transducer domains has been studied extensively. The dimeric fragment is competent for ATP hydrolysis and its structure in complex with the substrate analog AMPPNP is known. Here, we have determined the remaining conformational states of the enzyme along the ATP hydrolysis reaction path by solving crystal structures of GyrB43 in complex with ADP⋅BeF3, ADP⋅Pi, and ADP. Upon hydrolysis, the enzyme undergoes an obligatory 12° domain rearrangement to accommodate the 1.5 Å increase in distance between the γ- and β-phosphate of the nucleotide within the sealed binding site at the domain interface. Conserved residues from the QTK loop of the transducer domain (also part of the domain interface) couple the small structural change within the binding site with the rigid body motion. The domain reorientation is reflected in a significant 7 Å increase in the separation of the two transducer domains of the dimer that would embrace one of the DNA segments in full-length gyrase. The observed conformational change is likely to be relevant for the allosteric coordination of ATP hydrolysis with DNA binding, cleavage/re-ligation and/or strand passage.

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“…The gene duplication events that gave rise to these two complexes are very ancient, predating the split between Gram-negative and Gram-positive bacteria (e.g. Sissi & Palumbo, 2010). DNA gyrase and topoisomerase IV play important roles in DNA supercoiling and in the decatenation of closed circular DNA molecules.…”

Section: Quinolone Targets and Mechanisms Of Resistancementioning

confidence: 99%

Parallel evolution and local differentiation in quinolone resistance in Pseudomonas aeruginosa

Wong

Kassen

2011

Microbiology

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The emergence and spread of antibiotic resistance in pathogens is a major impediment to the control of microbial disease. Here, we review mechanisms of quinolone resistance in Pseudomonas aeruginosa, an important nosocomial pathogen and a major cause of morbidity in cystic fibrosis (CF) patients. In this quantitative literature review, we find that mutations in DNA gyrase A, the primary target of quinolones in Gram-negative bacteria, are the most common resistance mutations identified in clinical samples of all origins, in keeping with previous observations. However, the identities of non-gyrase resistance mutations vary systematically between samples isolated from CF patients and those isolated from acute infections. CF-derived strains tend to harbour mutations in the efflux pump regulator nfxB, while non-CF strains tend to bear mutations in the efflux regulator mexR or in parC, which encodes one of two subunits of DNA topoisomerase IV. We suggest that differences in resistance mechanisms between CF and non-CF strains result either from local adaptation to different sites of infection or from differences in mutational processes between different environments. We further discuss the therapeutic implications of local differentiation in resistance mechanisms to a common antibiotic.

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In front of and behind the replication fork: bacterial type IIA topoisomerases

Cited by 78 publications

References 189 publications

Adenylylation of Gyrase and Topo IV by FicT Toxins Disrupts Bacterial DNA Topology

Adenylylation of Gyrase and Topo IV by FicT Toxins Disrupts Bacterial DNA Topology

Structure of the N-Terminal Gyrase B Fragment in Complex with ADP⋅Pi Reveals Rigid-Body Motion Induced by ATP Hydrolysis

Parallel evolution and local differentiation in quinolone resistance in Pseudomonas aeruginosa

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