Present in all organisms, DNA ligases catalyse the formation of a phosphodiester bond between a 3′ hydroxyl and a 5′ phosphate, a reaction that is essential for maintaining genome integrity during replication and repair. Eubacterial DNA ligases use NAD+ as a cofactor and possess low sequence and structural homology relative to eukaryotic DNA ligases which use ATP as a cofactor. These key differences enable specific targeting of bacterial DNA ligases as an antibacterial strategy. In this study, four small molecule accessible sites within functionally important regions of Escherichia coli ligase (EC-LigA) were identified using in silico methods. Molecular docking was then used to screen for small molecules predicted to bind to these sites. Eight candidate inhibitors were then screened for inhibitory activity in an in vitro ligase assay. Five of these (geneticin, chlorhexidine, glutathione (reduced), imidazolidinyl urea and 2-(aminomethyl)imidazole) showed dose-dependent inhibition of EC-LigA with half maximal inhibitory concentrations (IC50) in the micromolar to millimolar range (11–2600 µM). Two (geneticin and chlorhexidine) were predicted to bind to a region of EC-LigA that has not been directly investigated previously, raising the possibility that there may be amino acids within this region that are important for EC-LigA activity or that the function of essential residues proximal to this region are impacted by inhibitor interactions with this region. We anticipate that the identified small molecule binding sites and inhibitors could be pursued as part of an antibacterial strategy targeting bacterial DNA ligases.
No abstract
A novel Coronavirus disease (COVID-19) has being originated from animals and causing to running outbreak of viral pneumonia in human all over the world. The World Health Organization (WHO) has considered COVID-19 infection as Epidemic disease in March 2020. The high percentages of death rate among people lead the researchers and scientists in different fields of medicine in order to find solution for this threating problem. In this regard, an editing gene technique was employed in this study, in order to deter the viability of coronavirus genetically. The main objective in this paper first has been determined and obtained the essential proteins of COVID-19 coronavirus proliferation by using NCBI website which included S, E, N, M, ORF3a, ORF6, ORF7a, ORF7b, ORF8, ORF10 proteins. The second objective is to use a very precise technique of editing gene called CRISPR-Cas9 to make changes to the virus’s RNA, through designing single-guide RNA for the essential each protein of COVID-19, in order to inactivate an effective certain protein. These techniques will be provided for each patient and healthy person by injection of all genes components using the Gene-gun machine or spray aerosol to make ensure reach it to the target cell.
Pollution in general is constantly increasing being polluted by environmental pollution with heavy metals that may be located in air, soil, water, or even food. In spite of being bacteria in general are harmful to humans, they are sometimes considered very valuable and safety, especially in biological treatment like probiotic bacteria group. Lactobacillus salivarius one of the maximum essential sorts of microorganism which are harmless to human and that may be play very capability position to cast off and removal heavy metals in different media. The main object in this study is extract bacteriocin TXJ for Lactobacillus salivarius isolated from Greek yogurt, which performs very important function by experimentally in biological reaction to the different heavy metal ions and reduce their concentrations and hopefully to using in the near future for treatment and reduce the pollution in the environment. This project there were used three various concentrations 20, 40, 60 PPM for five main heavy metals (Cu, Cd, Pb, Cr and Zn), which were added to extracted bacteriocin. Atomic absorption technique was used for determine the levels of heavy metal. Furthermore, the experiment was recorded based on the comparison for before and after adding bacteriocin protein at the lab.
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