Therapeutic options including last-line or combined antibiotic therapies for multi-drug-resistant strains of
Acinetobacter baumannii
are ineffective. The outer membrane protein A (OmpA) and outer membrane protein W (OmpW) are two porins known for their different cellular functions. Identification of natural compounds with the potentials to block these putative porins can attenuate the growth of the bacteria and control the relating diseases. The current work aimed to screen a library of 384 phytochemicals according to their potentials to be used as a drug, and potentials to inhibit the function of OmpA and OmpW in
A. baumannii
. The phytocompounds were initially screened based on their physico-chemical, absorption, distribution, metabolism, excretion and toxicity (ADMET) drug-like properties. Afterwards, the selected ligands were subjected to standard docking calculations against the predicted three-dimensional structure of OmpA and OmpW in
A. baumannii
. We identified three phytochemicals (isosakuranetin, aloe-emodin and pinocembrin) possessing appreciable binding affinity towards the selected binding pocket of OmpA and OmpW. Molecular dynamics simulation analysis confirmed the stability of the complexes. Among them, isosakuranetin was suggested as the best phytocompound for further
in vitro
and
in vivo
study.
Objectives Extensive applications of peroxidase (POX) have raised the global market demand at a considerable rate during the forecast period of 2020 -2025. Nonetheless, the large-scale POX preparation still relies on the extraction from agricultural products, while there is an accumulative driving force toward employing biotechnological processes with agricultural hassle free identity. In pursuit of this trend; Results, A novel heme peroxidase was puri ed to homogeneity (MW of 40 kD) from the callus culture of Ocimum basilicum L. in darkness on Murashige-Skoog medium supplemented by 2,4dichlorophenoxyacetic acid (10 -6 M) and kinetin (10 -5 M). The highest activity of the puri ed peroxidase (ObPOX) was observed in Tris-base buffer at pH 7.5 and 80 °C. ObPOX showed high stability over pH(s) 5 to 7.5 and temperatures of 15 to 60 °C. ObPOX speci c activity was 1245.142 AU mg -1 in the presence of phenol, 4 times higher than that of HRP. ObPOX showed moderate a nity for guaiacol (K m = 21.5 mM), but obtained an exceptionally high speci city constant (k cat /K m = 66743.7 s -1 M -1 ) for GASA (4-[(4-Hydroxy-3-methoxyphenyl) azo]-benzenesulfonic acid), the introduced substrate for determination of blood sugar. Applying ObPOX instead of HRP in glucose measurements of the real samples improved the regression constant of the correlation diagram between the tests and the lab results from 0.958 to 0.981.Conclusion Physicochemical properties of ObPOX as well as the growth rate of basil callus (5.04 g L -1 per day) and the yield of ObPOX production (35 mg per 100 g dry biomass per subculture) designates O. basilicum cell culture for large-scale production of a robust peroxidase.
SummaryTherapeutic options, including last-line or combined antibiotic therapies for multi-drug resistant (MDR) strains of Acinetobacter baumannii are ineffective. The outer membrane protein A (OmpA) and outer membrane protein W (OmpW) are two porins known for their different cellular functions. Identification of natural compounds with the potentials to block these putative porins can attenuate the growth of the bacteria and control the relating diseases. The current work aimed to screen a library of 384 phytochemicals according to their potentials to be used as a drug, and potentials to inhibit the function of OmpA and OmpW in A. baumannii. The phytocompounds were initially screened based on their physicochemical, absorption, distribution, metabolism, excretion, and toxicity (ADMET) drug-like properties. Afterward, the selected ligands were subjected to standard docking calculations against the predicted three-dimensional structure of OmpA and OmpW in A. baumannii. We identified three phytochemicals (isosakuranetin, aloe-emodin and pinocembrin) possessing appreciable binding affinity towards the selected binding pocket of OmpA and OmpW. Molecular dynamics (MD) simulation analysis confirmed the stability of the complexes. Amongst them, isosakuranetin was suggested as the best phytocompound for further in vitro and in vivo study.
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