Background: The emergence of antibiotic-resistant pathogens generates impairment to human health. U1-SCTRX-lg1a is a peptide isolated from a phospholipase D extracted from the spider venom of Loxosceles gaucho with antimicrobial activity against Gram-negative bacteria (between 1.15 μM to 4.6 μM). The aim of this study was to suggest potential receptors associated with the antimicrobial activity of U1-SCTRX-lg1a using in silico bioinformatics tools.
Methods: The search for potential targets of U1-SCRTX-lg1a was performed using the PharmMapper server. Molecular docking between U1-SCRTX-lg1a and the receptor was performed using PatchDock software. The prediction of ligand sites for each receptor was conducted using the PDBSum server. Chimera 1.6 software was used to perform molecular dynamics simulations only for the best dock score receptor. In addition, U1-SCRTX-lg1a and native ligand interactions were compared using AutoDock Vina software. Finally, predicted interactions were compared with the ligand site previously described in the literature.
Results and discussion: The bioprospecting of U1-SCRTX-lg1a resulted in the identification of forty-nine intracellular proteins originating from Gram-negative microorganisms. Among these, NH3-dependent NAD+ synthetase showed the highest dock score. This result suggests that the peptide derived from brown spider venom may interact with residues SER48 and THR160. In addition, the C-terminus has greater affinity for the receptor than the N-terminus.
Conclusion: The in silico bioprospecting of receptors suggests that U1-SCRTX-lg1a may interfere with NAD+ production in Escherichia coli, a Gram-negative bacterium, altering the homeostasis of the microorganism and impairing growth.
Background
The emergence of resistant bacterial strains against traditional antibiotics and treatments increases each year. Doderlin is a cationic and amphiphilic peptide active against gram-positive, gram-negative and yeast stains. The aim of the present work was to identify potential receptors associated with the antimicrobial activity of Doderlin using in silico bioinformatics tools.
Methods
To search for potential targets of Doderlin, PharmMapper software was used. Molecular docking between Doderlin and the receptor was performed by PatchDock. Additional interaction and ligand site prediction for each receptor was performed by I-TASSER software.
Results
Those PDB, 1XDJ (11746), 1JMH (11046), 1YR3 (10578), and 1NG3 (10082), showed the highest dock score. Doderlin was found to be predicted/co-localized with A and B, enzymes accountable for nitrogenic bases.
Conclusion
The resulting receptor bioprospecting is highly correlated and suggests that Doderlin might act by interfering with DNA metabolism/production of bacteria, altering microorganism homeostasis and growth impairment.
To evaluate the effects of açai extract (EA) on oxidative stress and inflammation induced by high glucose in cultured mouse immortalized mesangial cells (MiMC) and diabetic rats. MiMC cell viability and proliferation were determined by MTT. Extracellular and intracellular nitric oxide (NO) and intracellular ROS were also measured. The cell proteins were extracted for analysis of catalase, Nrf2, p-Nrf2, SOD-1, SOD-2, iNOS, NF-κB, p-NF-κB and TNF-α expression. Male, adult Wistar rats were distributed into 3 groups: control (CTL) and diabetic (DM) rats who received water and DMEA and received 1 mL/day EA (200 mg/kg) via gavage for 8 consecutive weeks. After treatment with EA, metabolic profile, renal function and thiobarbituric acid reactives substances (TBARS) levels were evaluated, and kidneys were collected for qualitative histological analysis. EA maintained cell viability above 90% in all groups; it decreased proliferation in the HG group, both significant. NO levels, ROS generation, iNOS, NF-κB, p-NF-κB and TNF-α expression were reduced significantly after 72 h of EA treatment, with significant increases for all antioxidants studied. DMEA vs DM showed a significant increase in body weight, improved kidney function and reduced TBARS excretion. EA treatment decreased proliferation, oxidative stress and inflammation in MiMC, and although açai did not decrease fasting glucose, it recovered the body weight and delayed the decline of renal function in the diabetic animals, suppressing the signaling of inflammatory mediators via NF-κB inactivation and increasing all antioxidants studied by upregulating the Nrf2 response pathway.
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