Basic residues at the C-gate of DNA gyrase are involved in DNA supercoiling

Smith, Eric M.; Mondragón, Alfonso

doi:10.1016/j.jbc.2021.101000

Cited by 4 publications

(1 citation statement)

References 32 publications

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“…It is composed of two chains, GyrA and GyrB subunits that are responsible for the producing negative supercoils in DNA during replication [ 36 ]. Antimicrobials that target DNA gyrase exhibit their antibacterial activity by two mechanisms, as gyrase inactivation or by interfering with the normal ATP binding at a specific site [ 37 ]. Compared to the use of pyrazoles alone, it is likely that the combination of pyrazoles/T21 increases the intracellular concentration of pyrazoles, which leads to the increased inactivation of bacterial gyrase ( Figure 10 ).…”

Section: Discussionmentioning

confidence: 99%

Polysorbate 21 Can Modulate the Antibacterial Potential of Two Pyrazol Derivatives

Aonofriesei

2022

Biomolecules

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The combination of two compounds with known antimicrobial activity may, in some cases, be an effective way to limit the resistance to antibiotics of specific pathogens. Molecules carrying pyrazole moiety are well known for their bioactive properties and have wide applicability in the medical and pharmaceutical field. Surfactants have, among other useful properties, the ability to affect the growth of microorganisms. The paper reports on the effect of the combination of two pyrazole derivatives, (1H-pyrazol-1-yl) methanol 1-hydroxymethylpyrazole (SAM1) and 1,1′methandiylbis (1H–pyrazol) (AM1), with sorbitan monolaurate (polysorbate 21, Tween 21, T21) on the growth of Gram-positive and Gram-negative bacteria. The results demonstrated a different ability of this combination to inhibit Staphylococcus aureus and Escherichia coli. T21 intensified the inhibitory activity of the pyrazoles to a greater extent in the Gram-negative bacteria compared to the Gram-positive ones, a fact confirmed by time-kill experiments. The experimental data showed that the association of T21 with the pyrazoles led to the increased release of intracellular material and a more intense uptake of crystal violet, which indicates that the potentiation of the antibacterial effect was based on the modification of the normal permeability of bacterial cells. T21 acted as a modulating factor and increased the permeability of the membrane, allowing the accelerated penetration of the pyrazoles inside the bacterial cells. This fact is important in controlling the global increase in microbial resistance to antibiotics and antimicrobials and finding viable solutions to overcome the antibiotic crisis. The paper highlights the possibility of using non-toxic surfactant molecules in antimicrobial combinations with practical applications. This could widen the range of adjuvants in applications which would be useful in the control of resistant microorganisms.

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Section: Discussionmentioning

confidence: 99%

Polysorbate 21 Can Modulate the Antibacterial Potential of Two Pyrazol Derivatives

Aonofriesei

2022

Biomolecules

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Topoisomerases as targets for halting bacterial DNA replication

Gupta,

Sachdeva,

Salman

et al. 2025

Bacterial Enzymes as Targets for Drug Discovery

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Structures of African swine fever virus topoisomerase complex and their implications

Yang,

Shao,

Zhao

et al. 2024

Nat Commun

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African swine fever virus (ASFV) is the causal agent of African swine fever (ASF), which is contagious and highly lethal to domestic pigs and wild boars. The genome of ASFV encodes many proteins important for ASFV life cycle. The functional importance of topoisomerase Asfv TopII has been confirmed by in vivo and in vitro assays, but the structure of Asfv TopII is poorly studied. Here, we report four Asfv TopII complex structures. The ATPase domain structures reveal the detailed basis for ATP binding and hydrolysis, which is shared by Asfv TopII and eukaryotic TopIIs. The DNA-bound structures show that Asfv TopII follows conserved mechanism in G-DNA binding and cleavage. Besides G-DNA, a T-DNA fragment is also captured in one Asfv TopII structure. Mutagenesis and in vitro assays confirm that Pro852 and the T-DNA-binding residue Tyr744 are important for the function of Asfv TopII. Our study not only advances the understanding on the biological function of Asfv TopII, but also provides a solid basis for the development of Asfv TopII-specific inhibitors.

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Basic residues at the C-gate of DNA gyrase are involved in DNA supercoiling

Cited by 4 publications

References 32 publications

Polysorbate 21 Can Modulate the Antibacterial Potential of Two Pyrazol Derivatives

Polysorbate 21 Can Modulate the Antibacterial Potential of Two Pyrazol Derivatives

Topoisomerases as targets for halting bacterial DNA replication

Structures of African swine fever virus topoisomerase complex and their implications

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