Search results for "Proteins"
showing 10 items of 10069 documents
Secondary structure and dynamics study of the intrinsically disordered silica-mineralizing peptide P5S3during silicic acid condensation and silica de…
2017
The silica forming repeat R5 of sil1 from Cylindrotheca fusiformis was the blueprint for the design of P5 S3 , a 50-residue peptide which can be produced in large amounts by recombinant bacterial expression. It contains 5 protein kinase A target sites and is highly cationic due to 10 lysine and 10 arginine residues. In the presence of supersaturated orthosilicic acid P5 S3 enhances silica-formation whereas it retards the dissolution of amorphous silica (SiO2 ) at globally undersaturated concentrations. The secondary structure of P5 S3 during these 2 processes was studied by circular dichroism (CD) spectroscopy, complemented by nuclear magnetic resonance (NMR) spectroscopy of the peptide in …
Biophysical and functional characterization of the human olfactory receptor OR1A1 expressed in a mammalian inducible cell line
2014
International audience; Olfactory receptors (ORs) play a crucial role in detecting the odorant molecules present in the surrounding environment. These receptors, which belong to class A G-protein-coupled receptors, constitute the largest transmembrane protein family in the human genome. Functional studies showed that the OR family includes members that are able to respond to a large set of odorants and members that are activated by a relatively small number of related odorants. To understand the molecular mechanisms that govern the receptor-ligand interactions, we overexpressed the human OR hOR1A1 in a stable tetracycline-inducible HEK293S cell line. This receptor was engineered by insertin…
Effect of high pressure on the antimicrobial activity and secondary structure of the bacteriocin nisin
2018
International audience; Effect of high pressure (HP) treatment on the antimicrobial properties and the structure of nisin was evaluated. Nisin solutions at pH 2.8 or 6.1 were treated by HP at 500 MPa – 10 min – 20 °C and their antimicrobial potency was determined. It appeared that HP clearly impacted the antimicrobial activity of nisin, with respective activity loss of 22.5% and 49.9% at pH 2.8 and 6.1. Structural analysis of nisin by circular dichroism and Fourier transform-infrared spectroscopies revealed that the decrease of nisin antimicrobial activity was likely due to the unfolding of the protein induced by HP. A loss of nisin β-turns structure, particularly significant at neutral pH,…
Enhanced autophagic-lysosomal activity and increased BAG3-mediated selective macroautophagy as adaptive response of neuronal cells to chronic oxidati…
2019
Oxidative stress and a disturbed cellular protein homeostasis (proteostasis) belong to the most important hallmarks of aging and of neurodegenerative disorders. The proteasomal and autophagic-lysosomal degradation pathways are key measures to maintain proteostasis. Here, we report that hippocampal cells selected for full adaptation and resistance to oxidative stress induced by hydrogen peroxide (oxidative stress-resistant cells, OxSR cells) showed a massive increase in the expression of components of the cellular autophagic-lysosomal network and a significantly higher overall autophagic activity. A comparative expression analysis revealed that distinct key regulators of autophagy are upregu…
Artemisinin-treatment in pre-symptomatic APP-PS1 mice increases gephyrin phosphorylation at Ser270: a modification regulating postsynaptic GABAAR den…
2021
Abstract Artemisinins, a group of plant-derived sesquiterpene lactones, are efficient antimalarial agents. They also share anti-inflammatory and anti-viral activities and were considered for treatment of neurodegenerative disorders like Alzheimer’s disease (AD). Additionally, artemisinins bind to gephyrin, the multifunctional scaffold of GABAergic synapses, and modulate inhibitory neurotransmission in vitro. We previously reported an increased expression of gephyrin and GABAA receptors in early pre-symptomatic stages of an AD mouse model (APP-PS1) and in parallel enhanced CDK5-dependent phosphorylation of gephyrin at S270. Here, we studied the effects of artemisinin on gephyrin in the brain…
The NG2 Protein Is Not Required for Glutamatergic Neuron-NG2 Cell Synaptic Signaling.
2014
NG2 glial cells (as from now NG2 cells) are unique in receiving synaptic input from neurons. However, the components regulating formation and maintenance of these neuron–glia synapses remain elusive. The transmembrane protein NG2 has been considered a potential mediator of synapse formation and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) clustering, because it contains 2 extracellular Laminin G/Neurexin/Sex Hormone-Binding Globulin domains, which in neurons are crucial for formation of transsynaptic neuroligin– neurexin complexes. NG2 is connected via Glutamate Receptor-Interacting Protein with GluA2/3-containing AMPARs, thereby possibly mediating receptor clus…
Influence of pathway topology and functional class on the molecular evolution of human metabolic genes
2018
Metabolic networks comprise thousands of enzymatic reactions functioning in a controlled manner and have been shaped by natural selection. Thanks to the genome data, the footprints of adaptive (positive) selection are detectable, and the strength of purifying selection can be measured. This has made possible to know where, in the metabolic network, adaptive selection has acted and where purifying selection is more or less strong and efficient. We have carried out a comprehensive molecular evolutionary study of all the genes involved in the human metabolism. We investigated the type and strength of the selective pressures that acted on the enzyme-coding genes belonging to metabolic pathways …
Molecular basis of SARS-CoV-2 infection and rational design of potential antiviral agents: Modeling and simulation approaches
2020
International audience; The emergence in late 2019 of the coronavirus SARS-CoV-2 has resulted in the breakthrough of the COVID-19 pandemic that is presently affecting a growing number of countries. The development of the pandemic has also prompted an unprecedented effort of the scientific community to understand the molecular bases of the virus infection and to propose rational drug design strategies able to alleviate the serious COVID-19 morbidity. In this context, a strong synergy between the structural biophysics and molecular modeling and simulation communities has emerged, resolving at the atomistic level the crucial protein apparatus of the virus and revealing the dynamic aspects of k…
The Binding Mechanism of Epolactaene to Hsp60 Unveiled by in Silico Modelling
2016
Molecular Dynamics (MD) simulations and DFT/MM calculations were performed in order to rationalize available experimental results and to provide structural details on the binding mechanism of Epolactaene (EPO) to the 60 KDa Heat Shock Protein (Hsp60). The available crystal structure of Hsp60 represents the last step of the chaperone folding cycle, while the Hsp60-EPO complex was obtained by using a homology model of Hsp60, in order to simulate a state related to the beginning of the folding cycle (Rs1). The results of MD simulations point out that EPO shows the highest binding affinity for the empty ATP binding site. The presence of ATP opens a channel that allows the entrance of both EPO d…
In silico drug discovery of major metabolites from spices as SARS-CoV-2 main protease inhibitors
2020
Coronavirus Disease 2019 (COVID-19) is an infectious illness caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), originally identified in Wuhan, China (December 2019) and has since expanded into a pandemic. Here, we investigate metabolites present in several common spices as possible inhibitors of COVID-19. Specifically, 32 compounds isolated from 14 cooking seasonings were examined as inhibitors for SARS-CoV-2 main protease (Mpro), which is required for viral multiplication. Using a drug discovery approach to identify possible antiviral leads, in silico molecular docking studies were performed. Docking calculations revealed a high potency of salvianolic acid A and curcu…