Search results for "ylid"
showing 10 items of 1155 documents
Negatively Charged Gangliosides Promote Membrane Association of Amphipathic Neurotransmitters
2018
Lipophilic neurotransmitters (NTs) such as dopamine are chemical messengers enabling neurotransmission by adhering onto the extracellular surface of the post-synaptic membrane in a synapse, followed by binding to their receptors. Previous studies have shown that the strength of the NT-membrane association is dependent on the lipid composition of the membrane. Negatively charged lipids such as phosphatidylserine, phosphatidylglycerol, and phosphatidic acid have been indicated to promote NT-membrane binding, however these anionic lipids reside almost exclusively in the intracellular leaflet of the post-synaptic membrane instead of the extracellular leaflet facing the synaptic cleft. Meanwhile…
The IgGFc-binding protein FCGBP is secreted with all GDPH sequences cleaved but maintained by interfragment disulfide bonds
2021
Mucus forms an important protective barrier that minimizes bacterial contact with the colonic epithelium. Intestinal mucus is organized in a complex network with several specific proteins, including the mucin-2 (MUC2) and the abundant IgGFc-binding protein, FCGBP. FCGBP is expressed in all intestinal goblet cells and is secreted into the mucus. It is comprised of repeated von Willebrand D (vWD) domain assemblies, most of which have a GDPH amino acid sequence that can be autocatalytically cleaved, as previously observed in the mucins MUC2 and mucin-5AC. However, the functions of FCGBP in the mucus are not understood. We show that all vWD domains of FCGBP with a GDPH sequence are cleaved and …
Life history adjustments to intestinal inflammation in a gut nematode.
2017
ABSTRACT Many parasitic nematodes establish chronic infections. This implies a finely tuned interaction with the host immune response in order to avoid infection clearance. Although a number of immune interference mechanisms have been described in nematodes, how parasites adapt to the immune environment provided by their hosts remains largely unexplored. Here, we used the gastrointestinal nematode Heligmosomoides polygyrus to investigate the plasticity of life history traits and immunomodulatory mechanisms in response to intestinal inflammation. We adopted an experimental model of induced colitis and exposed worms to intestinal inflammation at two different developmental stages (larvae and …
Early life infection and host senescence
2018
IF 3.224 (2017); International audience; Advanced age is often associated with a chronic inflammatory status and inflammatory diseases. It has been suggested that exposure to infectious agents that stimulate the inflammatory response at early ages might have carry over effects in terms of accelerated senescence and increased mortality at late ages. However, not all pathogens and parasites have pro-inflammatory effects. In particular, parasitic nematodes have been shown to dampen the inflammatory response and to prevent or alleviate the symptoms of inflammatory diseases. We, therefore, tentatively predicted that early infection with a parasite that has anti-inflammatory properties might post…
Mechanistic study of the biosynthesis of R-phenylcarbinol by acetohydroxyacid synthase enzyme using hybrid quantum mechanics/molecular mechanics simu…
2021
Abstract The biosynthesis of R-phenylacetylcarbinol (R-PAC) by the acetohydroxy acid synthase, (AHAS) is addressed by molecular dynamics simulations (MD), hybrid quantum mechanics/molecular mechanics (QM/MM), and QM/MM free energy calculations. The results show the reaction starts with the nucleophilic attack of the C2α atom of the HEThDP intermediate on the Cβ atom of the carbonyl group of benzaldehyde substrate via the formation of a transition state (TS1) with the HEThDP intermediate under 4′-aminopyrimidium (APH+) form. The calculated activation free energy for this step is 17.4 kcal mol−1 at 27 °C. From this point, the reaction continues with the abstraction of Hβ atom of the HEThDP in…
A new class of phenylhydrazinylidene derivatives as inhibitors of Staphylococcus aureus biofilm formation
2016
In the struggle against the emergence of the antibiotic resistance, new molecules targeting biofilm formation could be useful as adjuvant of conventional antibiotics. This study focused on a new class of 2-phenylhydrazinylidene derivatives as antivirulence agents. The compound 12e showed interesting activities against biofilm formation of all tested Staphylococcus aureus strains with IC50 ranging from 1.7 to 43 µM; compounds 12f and 13a resulted strong inhibitors of S. aureus ATCC 6538 and ATCC 29213 biofilm formation with IC50 of 0.9 and 0.8 µM, respectively. A preliminary study on the mechanism of action was carried on evaluating the inhibition of sortase A transpeptidase. Compound 12e re…
Structural and functional insights into lysostaphin–substrate interaction
2018
Lysostaphin from Staphylococcus simulans and its family enzymes rapidly acquire prominence as the next generation agents in treatment of S. aureus infections. The specificity of lysostaphin is promoted by its C-terminal cell wall targeting domain selectivity towards pentaglycine bridges in S. aureus cell wall. Scission of these cross-links is carried out by its N-terminal catalytic domain, a zinc-dependent endopeptidase. Understanding the determinants affecting the efficiency of catalysis and strength and specificity of interactions lies at the heart of all lysostaphin family enzyme applications. To this end, we have used NMR, SAXS and molecular dynamics simulations to characterize lysostap…
A Perspective : Active Role of Lipids in Neurotransmitter Dynamics
2019
AbstractSynaptic neurotransmission is generally considered as a function of membrane-embedded receptors and ion channels in response to the neurotransmitter (NT) release and binding. This perspective aims to widen the protein-centric view by including another vital component—the synaptic membrane—in the discussion. A vast set of atomistic molecular dynamics simulations and biophysical experiments indicate that NTs are divided into membrane-binding and membrane-nonbinding categories. The binary choice takes place at the water-membrane interface and follows closely the positioning of the receptors’ binding sites in relation to the membrane. Accordingly, when a lipophilic NT is on route to a m…
CCDC 145652: Experimental Crystal Structure Determination
2000
Related Article: S.Fustero, M.Garcia de la Torre, M.C.Ramirez de Arellano|2000|Acta Crystallogr.,Sect.C:Cryst.Struct.Commun.|56|e213|doi:10.1107/S0108270100005217
CCDC 2090126: Experimental Crystal Structure Determination
2021
Related Article: Chris Gendy, J. Mikko Rautiainen, Aaron Mailman, Heikki M. Tuononen|2021|Chem.-Eur.J.|27|14405|doi:10.1002/chem.202102804